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The frequency of extreme drought events has been rising worldwide, but due to its unpredictability, how plants will respond remains poorly understood. Here, we aimed to characterize how the hydraulics and photosynthesis of savanna plants respond to extreme drought, and tested whether they can subsequently recover photosynthesis after drought. There was an extreme drought in 2019 in Southwest (SW) China. We investigated photosynthetic gas exchange, leaf-, stem-, and whole-shoot hydraulic conductance of 18 plant species with diverse leaf habits (deciduous, semi-deciduous and evergreen) and growth forms (tree and shrub) from a dry-hot valley savanna in SW China for three rainy seasons from 2019 to 2021. We also compared photosynthetic gas exchange to those of a regular year (2014). We found that leaf stomatal and hydraulic conductance and maximum photosynthetic rate were significantly lower during the drought in 2019 than in the wetter years. In 2019, all studied plants maintained stomatal conductance at their minimum level observed, which could be related to high vapor pressure deficits (VPD, >2 kPa). However, no significant difference in stem and shoot hydraulic conductance was detected across years. The reductions in leaf hydraulic conductance and stomatal regulation under extreme drought might help keep the stem hydraulic function. Stomatal conductance and photosynthesis after drought (2020 and 2021) showed comparable or even higher values compared to that of 2014, suggesting high recovery of photosynthetic gas exchange. In addition, the response of hydraulic and photosynthetic traits to extreme drought was convergent across leaf habits and growth forms. Our results will help better understand the physiological mechanism underlying the response of savanna ecosystems to climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Mistletoes play important roles in biogeochemical cycles. Although many studies have compared nutrient concentrations between mistletoes and their hosts, no general patterns have been found and the nutrient uptake mechanisms in mistletoes have not been fully resolved. To address the water and nutrient relations in mistletoes compared with their hosts, we measured 11 nutrient elements, two isotope ratios and two leaf morphological traits for 11 mistletoe and 104 host species from four sites across a large environmental gradient in southwest China. Mistletoes had significantly higher phosphorus, potassium, and boron concentrations, nitrogen isotope ratio, and lower carbon isotope ratio (δ 13 C) indicative of lower water-use efficiency than hosts, but other elements were similar to those in hosts. Sites explained most of the variation in the multidimensional trait space. With increasing host nitrogen concentration, both mistletoe δ 13 C and the difference between mistletoe and host δ 13 C increased, providing evidence to support the 'nitrogen parasitism hypothesis'. Host nutrient concentrations were the best predictors for that of the mistletoe nutrient elements in most cases. Our results highlight the important roles of environmental conditions and host nutrient status in determining mistletoe nutrient pools, which together explain their trophic interactions with hosts in subtropical and tropical ecosystems., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton-a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C-C bond. Dryatraol D features a rare spiro [benzofuran-2',5″-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC 50 values of 11.9 μM and 5.5 μM, respectively. Dryatraols F-H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC 50 values ranging from 2.6 to 6.3 μM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Premise: Determining how xylem vessel diameters vary among plants and across environments gives insights into different water-use strategies among species and ultimately their distributions. Here, we tested the vessel dimorphism hypothesis that the simultaneous occurrence of many narrow and a few wide vessels gives lianas an advantage over trees in seasonally dry environments., Methods: We measured the diameters of 13,958 vessels from 15 liana species and 10,430 vessels from 16 tree species in a tropical seasonal rainforest, savanna, and subtropical evergreen broadleaved forest. We compared differences in mean and hydraulically weighted vessel diameter (MVD and D h ), vessel density (VD), theoretical hydraulic conductivity (K t ), vessel area fraction (VAF), and wood density (WD) between lianas and trees and among three sites., Results: Nine liana species and four tree species had dimorphic vessels. From the tropical seasonal rainforest to the savanna, liana MVD, D h and K t decreased, and VD and WD increased, while only tree WD increased. From the tropical seasonal rainforest to the subtropical forest, six wood traits remained unchanged for lianas, while tree MVD, D h and K t decreased and VD increased. Trait space for lianas and trees were more similar in the savanna and more divergent in the subtropical forest compared to the tropical seasonal rainforest., Conclusions: These results suggest that lianas tend to possess greater vessel dimorphism, which may explain how lianas grow well during seasonal drought, influencing their unique distribution across tropical rainfall gradients., (© 2023 Botanical Society of America.)

Achieving percolation pathways in a metal-organic framework (MOF)-based mixed matrix membrane (MMM) without compromising its mechanical properties is challenging. We developed phase separated (PS)-MMMs with an interconnected MOF domain running across the whole membrane. Through demixing two immiscible polyimides, the MOF particles were selectively partitioned into one of the preferred polymer domains at over 50 volume % local packing density, leading to a percolated network at only 19 weight % MOF loading. The CO 2 permeability of this PS-MMM is 6.6 times that of the pure polymer membrane, while the CO 2 /N 2 and CO 2 /CH 4 selectivity remain largely unchanged. Meanwhile, benefiting from its unique co-continuous morphology, the PS-MMM also exhibited markedly improved membrane ductility compared to the conventional MMM at similar MOF loading. PS-MMMs offer a practical solution to simultaneously achieve high membrane permeability and good mechanical properties.

Major chemical constituents in medicinal materials are often used as the marker compounds of traditional Chinese medicine (TCM) for treating various diseases. For spatholobi caulis (SPC), it contains a variety of flavones, phenolic acid esters, and lignans which exert many pharmacological effects. However, the absorption and permeability properties of these constituents of SPC are still unclear and require further investigation. Different types and major compounds of SPC were chosen as representative constituents to study their absorption and transepithelial transport characteristics in the human intestinal epithelium-like Caco-2 cell monolayer model. 35 constituents of SPC were evaluated by using ultra fast liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-MS/MS) method, acetonitrile and water containing with 0.5 mM ammonium acetate were used as mobile phase, these analytes with good linear relationships (R 2 was within 0.9967-0.9998), precision (CV values were less than 10.23 %, LLOQ was less than 13.69 %), accuracy (Mean of inter- and intra-day were within 85.02 %-111.61 % and 85.50-112.97 %, respectively) and stability (The mean was within 85.07 %-113.93 %), among which 16 analytes showed good permeability, 5 analytes were considered to be poorly permeable compounds, and the other 14 analytes were assigned for the moderately absorbed compounds in Caco-2 cell monolayer model. The further results showed that the absorption mechanism of 7 well absorbed compounds, 8-O-methylretusin (1), genistein (7), spasuberol B (16), naringenin (18), isoliquiritigenin (19), 4-hydroxy-3-methoxy cinnamic acid methyl ester (23) and (+)-epipinoresinol (31) in SPC was mainly passive diffusion, their bidirectional transport rate was correlated with the concentration and transport time. The chemical structures of these compounds could affect the permeability properties on the cell monolayer. This study demonstrated the utility of Caco-2 cell monolayer model for evaluating the absorption properties and initial mechanisms of compounds in SPC in vitro, and provided important basis for predicting oral bioavailability of SPC compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is one of the most common digestive system cancers with high mortality rates worldwide. The main ingredients in Mu Ji Fang Granules (MJF) are alkaloids, flavonoids, and polysaccharides. MJF has been used in the clinical treatment of hepatitis, cirrhosis and HCC for more than 30 years. Few previous studies have focused on the mechanism of MJF on tumor immu-nology in the treatment of HCC., Aim: To explore the mechanism of action of MJF on tumor immunology in the treatment of HCC., Methods: The absorbable ingredients of MJF were identified using Molecule Network related to High Performance Liquid Chromatography-Electron Spray Ionization-Time of Flight- Mass Spectrometry, and hub potential anti-HCC targets were screened using network pharmacology and pathway enrichment analysis. Forty male mice were randomly divided into the Blank, Model, and MJF groups (1.8, 5.4, and 10.8 g/kg/d) following 7 d of oral administration. Average body weight gain, spleen and thymus indices were calculated, tumor tissues were stained with hematoxylin and eosin, and Interferon gamma (IFN-γ), Tumor necrosis factor α (TNF-α), Interleukin-2, aspartate aminotransferase, alanine aminotransferase, alpha-fetoprotein (AFP), Fas, and FasL were measured by Enzyme-linked Immunosorbent Assay. Relevant mRNA expression of Bax and Bcl2 was evaluated by Real Time Quantitative PCR (RT-qPCR) and protein expression of Transforming growth factor β1 (TGF-β1) and Mothers against decapentaplegic homolog (SMAD) 4 was assessed by Western blotting. The HepG2 cell line was treated with 10 mg/mL, 20 mg/mL, 30 mg/mL, 40 mg/mL of MJF, and another 3 groups were treated with TGF-β1 inhibitor (LY364947) and different doses of MJF. Relevant mRNA expression of TNF-α, IFN-γ, Bax and Bcl2 was evaluated by RT-qPCR and protein expression of TGF-β1, SMAD2, p-SMAD2, SMAD4, and SMAD7 was assessed by Western blotting., Results: It was shown that MJF improved body weight gain and tumor inhibition rate in H22 tumor-bearing mice, protected immune organs and liver function, reduced the HCC indicator AFP, affected immunity and apoptosis, and up-regulated the TGF-β1/SMAD signaling pathway, by increasing the relative expression of TGF-β1, SMAD2, p-SMAD2 and SMAD4 and decreasing SMAD7, reducing immune factors TNF-α and IFN-γ, decreasing apoptosis cytokines Fas, FasL and Bcl2 / Bax , and inhibiting the effect of LY364947 in HepG2 cells., Conclusion: MJF inhibits HCC by activating the TGF-β1/SMAD signaling pathway, and affecting immune and apoptotic cytokines, which may be due to MJF adjusting immune escape and apoptosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The enantioselective conjugate addition of malonates to α,β-unsaturated aldehydes catalysed by 4-oxalocrotonate tautomerase is described. High conversions, high enantioselectivities, and good isolation yields were achieved for a range of substrates. We further completed a four-step synthesis of the antidepressant (+)-femoxetine by utilizing this reaction and an enzymatic reductive amination reaction.

This study explored the correlation between semaphorin 4D (SEMA4D) and the prognosis and survival time of patients with melanoma combined with liver cancer. A total of 272 patients were recruited, and clinical and follow-up data were recorded. The expression levels of SEMA4D and SEMA3B were determined. Pearson's χ 2 test and Spearman's rank correlation coefficient were used to analyze the relationship between prognosis and the assessed parameters of melanoma patients. Univariate and multivariate Logistic regression and Cox proportional risk regression analyses were used for further analysis. Additionally, receiver operating characteristic curve and survival curves of subjects were plotted. The Pearson's χ 2 test showed that the prognosis of melanoma patients was significantly correlated with age, tumor grade, and decreased SEMA4D expression. Additionally, Spearman's correlation coefficient analysis showed that age, tumor grade, and SEMA4D expression were significantly correlated with prognosis. Univariate logistic regression analysis showed that age and tumor grade, and SEMA4D expression, were significantly correlated with prognosis. Older patients, a higher tumor grade, and lower SEMA4D expression were associated with a poorer prognosis. Multivariate logistic regression analysis showed that older patients had a poorer prognosis, and patients with lower SEMA4D expression levels had a significantly worse prognosis than patients with higher SEMA4D expression levels. Kaplan-Meier analysis showed that the survival time of older patients was lower than that of the younger patients. The survival times of patients with lower SEMA4D expression levels were significantly lower than that of patients with higher SEMA4D expression levels. Multivariate Cox regression analysis showed that the survival time of older patients was lower than that of younger patients. The survival time of melanoma patients with low SEMA4D expression was significantly lower than that of patients with higher SEMA4D expression. SEMA4D was significantly associated with melanoma, and lower SEMA4D expression was associated with a poorer survival prognosis in melanoma patients., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Liu et al.)

Abstract: Aim: The purpose of this study was to investigate the effect of esmolol (ES) on LPS-induced cardiac injury and the possible mechanism. Methods: Sepsis was induced by i.p. injection of LPS (10 mg/kg) in male Sprague-Dawley rats pretreated with ES, 3-methyladenine or rapamycin. The severity of myocardial damage was analyzed by hematoxylin-eosin staining, and myocardial damage scores were calculated. The concentration of cardiac troponin was measured by enzyme-linked immunosorbent assay. The expression of autophagy-related proteins (beclin-1, LC3-II, p-AMPK, p-ULK1, p-mTOR) in myocardial tissue was detected by Western blotting. Autophagosome formation and the ultrastructural damage of mitochondria were assessed using transmission electron microscopy. Results: LPS induced an increase in myocardial damage score in a time-dependent manner, accompanied with an increase in autophagy at 3 h and decrease in autophagy at 6, 12, and 24 h. Pretreatment of LPS-treated rats with ES or rapamycin reduced myocardial injury (release of cardiac troponin, myocardial damage score) and increased autophagy (LC3-II, beclin-1, p-AMPK, and p-ULK1 levels and autophagosome numbers) at 12 and 24 h. In contrast, 3-methyladenine showed no effect. Conclusion: Esmolol alleviates LPS-induced myocardial damage through activating the AMPK/mTOR/ULK1 signal pathway-regulated autophagy., Competing Interests: The authors report no conflict of interests., (Copyright © 2023 by the Shock Society.)

Importance: Improved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts., Objectives: To characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups., Design, Setting, and Participants: This survey study included 20 430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022., Exposures: National Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018., Main Outcomes and Measures: Metabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis., Results: This study included 20 430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend)., Conclusions and Relevance: The findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.

Aim: To explore the prevalence and related factors influencing diabetes stigma among Chinese young and middle-aged patients with type 2 diabetes., Design: A cross-sectional, quantitative study was conducted through questionnaires., Methods: A total of 453 young and middle-aged patients with type 2 diabetes were recruited. Questionnaire survey was conducted with convenience sampling from September 2019 to December 2020. This included demographic questionnaire, Type 2 Diabetes Stigma Assessment Scale (DSAS-2) and Connor-Davidson Resilience Scale (CD-RISC). The STROBE checklist was applied as the reporting guideline for this study., Results: The scores of diabetes stigma and resilience of patients were 48.18 ± 14.52 and 66.02 ± 7.18, respectively. Diabetes stigma was negatively correlated with resilience, the correlation coefficient was -0.581. The results showed that the complications, diabetes year, monthly income and insulin treatment are important factors affecting stigma. In addition, it is resilience that was a protective factor of diabetes stigma, explaining 27.2% of the variance in diabetes stigma., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Excessive, high doses of ultraviolet B (UVB) UVB irradiation are known to cause skin cancer, aging and immunosuppression. On the contrary, moderate low doses of UVB irradiation are shown to be essential and beneficial to human health, including a tumor-suppressive effect. However, the mechanism by which low levels of UVB suppress tumorigenesis remains unclear. Here, using tumor-bearing mouse models, we show that moderate low repetitive UVB irradiation increases the percentage of activated CD4 + and CD8 + T cells, and CD103 + conventional type 1 dendritic cells (cDC1s), while it decreases the number of immunosuppressive, M2-like macrophages in the tumors. Finally, in mice, deletion of Batf3, a transcription factor critical for the development of conventional dendritic cells, including the CD103 + cDC1s, showed increased tumor growth in both sham- and UVB-irradiated mice. Our findings demonstrate that moderate low UVB irradiation inhibits M2-like tumor-associated macrophages, increases CD103 + cDC1s and promotes antitumor immunity in mice with an established tumor., (© 2022 American Society for Photobiology.)

In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what is the exact role for a certain fish herc7 gene. Here, a total of four herc7 genes (named HERC7a-d sequentially) are identified in the zebrafish genome. They are transcriptionally induced by a viral infection, and detailed promoter analyses indicate that zebrafish herc7c is a typical interferon (IFN)-stimulated gene. Overexpression of zebrafish HERC7c promotes SVCV (spring viremia of carp virus) replication in fish cells and concomitantly downregulates cellular IFN response. Mechanistically, zebrafish HERC7c targets STING, MAVS, and IRF7 for protein degradation, thus impairing cellular IFN response. Whereas the recently-identified crucian carp HERC7 has an E3 ligase activity for the conjugation of both ubiquitin and ISG15, zebrafish HERC7c only displays the potential to transfer ubiquitin. Considering the necessity for timely regulation of IFN expression during viral infection, these results together suggest that zebrafish HERC7c is a negative regulator of fish IFN antiviral response.

Galactosylated core-shell nanoparticles (NPs) with diameters of sub-50 nm were fabricated in one pot by reversible addition-fragmentation chain transfer (RAFT) soap-free emulsion polymerization. Their galactosylated shells and acidic cores endow them with high targeting and drug loading efficiencies, respectively. Morever, the physical shrinkage and cleavage of the disulfide cross-linked NPs can realize the rapid release of loaded doxorubicin (DOX) under pH 5.0 and reduced glutathione (GSH) conditions. The combination of these excellent properties resulted in an even lower IC 50 of DOX-loaded NPs than free DOX, demonstrating that this platform would be promising in targeting the therapy of hepatocellular carcinoma.

Background: Cancer-related fatigue is a widely prevalent global public health concern with serious consequences. Increasing evidence suggests the effectiveness of exercise intervention in treating cancer-related fatigue, but there is a lack of a summary of relevant literature on the same to help reach a clear consensus., Objective: To summarize evidence regarding the efficacy of exercise interventions to reduce cancer fatigue, as determined in systematic reviews (SRs) and/or meta-analyses (MAs)., Method: From inception to September 2022, PubMed (1948-2022), Embase (1974-2022), Cochrane Library (1993-2022), CINAHL (1937-2022), Web of Science (1997-2022), China Knowledge Resource Integrated Database (1999-2022), Wanfang Database (1993-2022), and Chinese Biomedical Database (1994-2022) were searched for inclusion to the study. Two reviewers independently extracted the data from the included articles. AMSTAR II was to evaluate the methodological quality of the reviews., Results: A total of 46 systematic reviews were assessed for data on exercise intervention in reducing cancer-related fatigue among cancer patients. In addition, some studies have reported adverse events during the exercise intervention period. The quality of the included systematic review was found to be low or critically low., Conclusions: The present systematic review of systematic reviews supports exercise intervention for reducing cancer-related fatigue. Further higher-quality studies are warranted to improve the level of evidence for exercise interventions for application in the treatment of cancer-related fatigue., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements., Background: Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries., Methods: In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.5 mg oral pemigatinib once daily (3-week cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee., Results: As of January 29, 2021, 31 patients were enrolled. The median follow-up was 5.1 months (range, 1.5-9.3). Among 30 patients with FGFR2 fusions or rearrangements evaluated for efficacy, 15 patients achieved partial response (ORR, 50.0%; 95% confidence interval [CI], 31.3-68.7); 15 achieved stable disease, contributing to a disease control rate of 100% (95% CI, 88.4-100). The median time to response was 1.4 months (95% CI, 1.3-1.4), the median duration of response was not reached, and the median progression-free survival was 6.3 months (95% CI, 4.9-not estimable [NE]). Eight (25.8%) of 31 patients had ≥grade 3 treatment-emergent adverse events. Hyperphosphatemia, hypophosphatasemia, nail toxicities, and ocular disorders were mostly

Maintaining open flowers is critical for successful pollination and depends on long-term water and carbon balance. Yet the relationship between how flower hydraulic traits are coordinated in different habitats is poorly understood. Here, we hypothesize that the coordination and trade-offs between floral hydraulics and economics traits are independent of environmental conditions. To test this hypothesis, we investigated a total of 27 flower economics and hydraulic traits in six aquatic and six terrestrial herbaceous species grown in a tropical botanical garden. We found that although there were a few significant differences, most flower hydraulics and economics traits did not differ significantly between aquatic and terrestrial herbaceous plants. Both flower mass per area and floral longevity were significantly positively correlated with the time required for drying full-hydrated flowers to 70% relative water content. Flower dry matter content was strongly and positively related to drought tolerance of the flowers as indicated by flower water potential at the turgor loss point. In addition, there was a trade-off between hydraulic efficiency and the construction cost of a flower across species. Our results show that flowers of aquatic and terrestrial plants follow the same economics spectrum pattern. These results suggest a convergent flower economics design across terrestrial and aquatic plants, providing new insights into the mechanisms by which floral organs adapt to aquatic and terrestrial habitats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Objective: To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes., Patients and Methods: Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020., Results: A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses., Conclusion: The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes., (Copyright © 2022 Mayo Foundation for Medical Education and Research. All rights reserved.)

Molecular recognition is an attractive approach to designing sensitive and selective sensors for volatile organic compounds (VOCs). Although organic macrocycles and cages have been well-developed for recognising organics by their adaptive pockets in liquids, porous solids for gas detection require a deliberate design balancing adaptability and robustness. Here we report a dynamic 3D covalent organic framework (dynaCOF) constructed from an environmentally sensitive fluorophore that can undergo concerted and adaptive structural transitions upon adsorption of gas and vapours. The COF is capable of rapid and reliable detection of various VOCs, even for non-polar hydrocarbon gas under humid conditions. The adaptive guest inclusion amplifies the host-guest interactions and facilitates the differentiation of organic vapours by their polarity and sizes/shapes, and the covalently linked 3D interwoven networks ensure the robustness and coherency of the materials. The present result paves the way for multiplex fluorescence sensing of various VOCs with molecular-specific responses., (© 2022. The Author(s).)

The craniofacial features endow vertebrates with unparalleled evolutionary advantages. The craniofacial is composed of bone, cartilage, nerves, and connective tissues mainly developed from cranial neural crest cells (cNCCs). These tissues form complex organs which enable vertebrates to have powerful neural and sensory systems. NCCs are groups of migratory and pluripotent cells that are specific to vertebrates. The specification, premigration and migration, proliferation, and fate determination of the NCCs are precisely and sequentially controlled by gene regulatory networks, to ensure the ordered and accurate development of the craniofacial region. The craniofacial region represents a combined set of highly heritable phenotypes, which could be illustrated by the inherited facial features between relatives but perceptible differences among non-relatives. Such phenomena are termed heredity and variation, which are in accordance with the precision and plasticity of cNCCs gene regulatory network, respectively. Evidence has shown that genetic variations within the regulatory network alter the proliferation and differentiation of NCCs within a tolerable range, while deleterious mutations will lead to craniofacial malformations. In this review, we first summarize the development procedure of NCCs and their gene regulatory networks and then provide an overview on the genetic basis of the facial morphology and malformations. This review will benefit the understanding of craniofacial development and the prevention of craniofacial diseases.

Many chronic diseases such as Alzheimer's disease, diabetes, and cardiovascular diseases are closely related to in vivo oxidative stress caused by excessive reactive oxygen species (ROS). Natural polysaccharides, as a kind of biomacromolecule with good biocompatibility, have been widely used in biomedical and medicinal applications due to their superior antioxidant properties. In this review, scientometric analysis of the highly cited papers in the Web of Science (WOS) database finds that antioxidant activity is the most widely studied and popular among pharmacological effects of natural polysaccharides. The antioxidant mechanisms of natural polysaccharides mainly contain the regulation of signal transduction pathways, the activation of enzymes, and the scavenging of free radicals. We continuously discuss the antioxidant activities of natural polysaccharides and their derivatives. At the same time, we summarize their applications in the field of pharmaceutics/drug delivery, tissue engineering, and antimicrobial food additives/packaging materials. Overall, this review provides up-to-date information for the further development and application of natural polysaccharides with antioxidant activities.

Here, we present a protocol to characterize zebrafish LGP2 as a dual regulator of interferon (IFN) response. We detail in vivo assays using time-lapse comparison of IFN response between wild-type and lgp2 knockout zebrafish following spring viraemia of carp virus (SVCV) infection. We also describe in vitro assays including titration of infection duration in SVCV-infected fish cells to determine changes in IFN response. This protocol is effective to illuminate a regulatory switch of LGP2 in fish cells toward virus infection. For complete details on the use and execution of this protocol, please refer to Gong et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Baofei Granules (BFGs) have been extensively applied in the clinical treatment of chronic obstructive pulmonary disease (COPD) and significantly have affected COPD patients with lung and spleen qi deficiency syndrome. However, the data from previous small-sample clinical trials are limited. This trial aimed to estimate the efficiency and safety of BFGs in COPD with lung and spleen qi deficiency syndrome., Methods: It is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. The 216 stable COPD patients will be divided randomly in a ratio of 1:1. The whole trial period consists of a 4-week introductory period, a 52-week treatment period and a 48-week follow-up. Study visits occur every 4 weeks during the treatment period and every 12 weeks during the follow-up. All the subjects will receive 10g BFGs or placebo three times per day for 56 weeks and be followed up for 48 weeks. The primary efficiency evaluation outcome will be the frequency and duration of AECOPD, and the secondary efficiency evaluation outcome will be pulmonary function tests (PFTs), modified Medical Research Council (mMRC) dyspnoea scale, six-minute walking test (6MWT), COPD assessment test (CAT) score, traditional Chinese medicine (TCM) syndrome score, the frequency of emergency medication, BODE index, and the time to first Clinically important deterioration (CID). The safety evaluation outcomes will be adverse events (AEs), vital signs, physical examination, twelve-lead electrocardiogram (ECG), and laboratory examinations. All the data will be analyzed by SAS9.4., Discussion: This is the first and largest clinical trial that evaluates the efficiency and safety of BFGs for COPD with lung and spleen qi deficiency syndrome. It will provide valuable clinical evidence for recommendations on COPD management by the integrated TCM and western medicine., Trial Registration: CTR20211280. Date: June 09, 2021. http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml?id=383a370ecd9f43d7af6f1c8585779e1a., Competing Interests: The authors declare that they have no competing interests., (© 2022 Sun et al.)

Aims/hypothesis: Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes., Methods: We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors., Results: During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups., Conclusions/interpretation: This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

This study aims to explore the chemical structure transformation mechanisms of the main terpenoids in the effective fraction of Euphorbiae Ebracteolatae Radix(EER) during the processing with vinegar. The terpenoids including ent-11α-hydroxyabicta-8(14),13(15)-dien-16,12-olide(HAO), jolkinolide B(JNB), fischeria A(FA), and eupractenoid A(EA) were heated at 160 ℃ with 6% acetic acid for 40 min, and then LC-MS/MS was employed to analyze the structural transformation rules of the terpenoids. Further, we analyzed the changes in the relative content of the four compounds and their transformation products in raw and vinegar processed EER to verify the transformation rules during the simulated processing with vinegar. In addition, JNB and FA were processed with single heating, heating with water or heating with acetic acid. We then employed HPLC to compare the content of these two terpenoids and their transformation products before and after processing, so as to investigate the effect of different processing methods on chemical structure transformation. The results showed that the lactone ring of the abietane-type diterpenoids HAO and JNB and the norditerpene lactone FA were opened by heating with acetic acid. When there were hydroxyl groups in the structures, terpenoids were esterized to esters and oxidized to form carbonyl groups. When there was epoxy ring in the structures, ring opening reaction was easy to occur. During the heating with acetic acid, the heterodimeric diterpenoid EA underwent the cleavage of ether bond to produce the rosane-type diterpenoid euphebracteolatin A(EHTA) and another abietane-type diterpenoid. The changes in the relative content of terpenoids and their transformation products in raw and vinegar-processed EER were basically consistent with those of simulated processing of components with vinegar. The HPLC results revealed that the effect of different simulated processing methods on structural transformation varied. Heating with acid can change JNB and FA into new components. Heating with water can also promote the structural transformation, with the efficiency obviously lower than that of heating with acid. Direct heating had no influence on the structure of JNB, while it significantly reduced the relative content of FA. The components treated with direct heating did not produce the products like those of the heating with acid. These results indicated that vinegar plays a key role in the structural transformation of diterpenoids during the processing of EER with vinegar. The structural transformation of diterpenoids in EER during the processing with vinegar may be the material basis for vinegar processed EER to reduce toxicity and preserve effect.

Understanding the regional propensity differences of atherosclerosis (AS) development is hindered by the lack of animal models suitable for the study of the disease process. In this paper, we used 3S-ASCVD dogs, an ideal large animal human-like models for AS, to interrogate the heterogeneity of AS-prone and AS-resistant arteries; and at the single-cell level, identify the dominant cells involved in AS development. Here we present data from 3S-ASCVD dogs which reliably mimic human AS pathophysiology, predilection for lesion sites, and endpoint events. Our analysis combined bulk RNA-seq with single-cell RNA-seq to depict the transcriptomic profiles and cellular atlas of AS-prone and AS-resistant arteries in 3S-ASCVD dogs. Our results revealed the integral role of smooth muscle cells (SMCs) in regional propensity for AS. Notably, TNC + SMCs were major contributors to AS development in 3S-ASCVD dogs, indicating enhanced extracellular matrix remodeling and transition to myofibroblasts during the AS process. Moreover, TNC + SMCs were also present in human AS-prone carotid plaques, suggesting a potential origin of myofibroblasts and supporting the relevance of our findings. Our study provides a promising large animal model for pre-clinical studies of ASCVD and add novel insights surrounding the regional propensity of AS development in humans, which may lead to interventions that delay or prevent lesion progression and adverse clinical events., Competing Interests: Competing interests The authors declare that they have no competing interests., (copyright: © 2022 Shi et al.)

Objective: The aim of the study was to investigate the clinical effect of single plane screw percutaneous internal fixation in the treatment of simple thoracolumbar fractures., Patients and Methods: The subjects of this study were 84 patients with simple thoracolumbar fractures treated in our hospital from January 2018 to December 2020. The patients were grouped by different treatment methods (42 cases in each group). The single plane group was treated by percutaneous single plane screw internal fixation and the universal group was treated with percutaneous universal screw. The surgery completion status and the incidence of complications were recorded. The visual analogue scale (VAS) and the Oswestry Disability Index (ODI) of the two groups were recorded before the surgery, 3 days after the surgery, and 7 days after the surgery. The anterior edge height ratio of the fractured vertebra and the kyphotic Cobb angle were marked before the surgery, immediately after the operation, and at the last follow-up., Results: Difference between groups in surgery time, blood loss and hospital stay was not statistically significant (p>0.05); the single plane group had a substantially lower incidence of complications than the universal group (p<0.05). At the last follow-up, the single plane group had greatly higher anterior edge height ratio of the injured vertebra than the universal group, while kyphotic Cobb angle was greatly higher in the universal group (p<0.05)., Conclusions: Both single plane screw and universal screw percutaneous internal fixation were feasible for the treatment of simple thoracolumbar fractures, but single plane screw showed better vertebral height recovery and kyphosis correction effect, which could reduce postoperative correction loss.

Objective: We present our initial experience using the microcatheter-guided compartment packing (MCP) technique for endovascular embolization of acutely ruptured complex intracerebral aneurysms (ARCIAs) and evaluate the safety, feasibility, and efficiency of this technique., Methods: This retrospective, single-center study included 28 patients who underwent coil embolization using the MCP technique for ARCIAs at our institution between January 2021 and January 2022. The MCP technique was the placement of microcatheters in different compartments within the aneurysm to deploy the coils simultaneously or sequentially. Patient demographics, aneurysm characteristics, procedural parameters, grade of occlusion, complications, and clinical results were analyzed. The clinical outcomes were evaluated with modified Rankin Scale (mRS) scores., Results: Of the 28 patients successfully treated with the MCP technique, 24 (85.7%) aneurysms were considered as complete occlusions (Raymond I) based on the immediate postembolization angiogram results. Complications occurred in 2/28 treatments, including guidewire perforation with subarachnoid hemorrhage and cerebral vasospasm-related cerebral infarction. An angiography follow-up demonstrated complete occlusion in 25/28 aneurysms. Twenty-six (92.9%) patients had favorable 90-day outcomes (mRS 0-2) after the endovascular coil embolization., Conclusion: The MCP technique is simple, safe, and effective, achieving good packing density and initial occlusion rate when used to treat ARCIAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Xie, Wang, Huang, Fan, Zhu, Chen, Wang, Yao, Yu, Dai, Kang and Zheng.)

Objective: We aimed to describe the initial experience of mechanical thrombectomy using tandem double stent retrievers combined with intermediate catheter aspiration to treat refractory severe hemorrhagic (SH)-cerebral venous sinus thrombosis (CVST)., Methods: All refractory SH-CVST patients treated with mechanical thrombectomy using tandem double stent retriever (SR) combined with intermediate catheter aspiration (MT-TDSA) in our institution were retrospectively reviewed. MT-TDSA is a technique that fully engages the clot with double SRs and retrieves the clot using a double SR in combination with aspiration from an intermediate catheter. Demographics, clinical manifestation, medical history, the location of the occluded venous sinus, intraoperative details, procedure-related complications, and modified Rankin Scale (1, 6, 12 months postoperatively) were collected and analyzed., Results: Fourteen patients (median age, 43 years) with refractory SH-CVST were treated with MT-TDSA between January 2016 and January 2020. Ten of 14 (71.4%) had a successful intraoperative recanalization rate (>90%) using MT-TDSA. No procedure-related complications occurred. Eleven patients had good clinical outcomes (modified Rankin Scale score 0-2 at 12 months postoperatively)., Conclusions: MT-TDSA for refractory SH-CVST might improve clot-capturing ability and remove blood clots from cerebral venous sinuses effectively and safely, achieving good clinical outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and mortality among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) remains unclear., Objective: The aim was to evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD., Methods: The study included 4651 individuals with fatty liver disease (FLD; 3964 had MAFLD and 3968 had NAFLD) from NHANES III. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the HRs and 95% CIs, with adjustment of potential confounders., Results: Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 y, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HRs and 95% CIs of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.001) and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.002). A nonlinear inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (P overall < 0.001; P nonlinear = 0.003) or NAFLD (P overall < 0.001; P nonlinear = 0.009), with a threshold effect at ∼50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged <60 y (P-interaction = 0.001)., Conclusions: This study suggested a nonlinear inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at ∼50.0 nmol/L of serum 25(OH)D., (Copyright © 2022 American Society for Nutrition.)

Di(2-ethylhexyl) phthalate (DEHP) is widely used and has been implicated in hepatotoxicity, although the mechanism is unclear. Here, we investigated the effect of DEHP on hepatic cholesterol metabolism in SD rats exposed to 0 and 300 mg/kg/day DEHP for 12 weeks. An RNA-Seq analysis was performed to describe the hepatic responses to long-term DEHP exposure in combination with serological and oxidative stress parameter measurements. DEHP increased the serum levels of total cholesterol (TC), high-density lipoprotein (HDL), and alanine transaminase (ALT). Moreover, DEHP increased the content of malondialdehyde (MDA) and decreased antioxidant enzyme activities in the liver. Transcriptomic results revealed that DEHP dramatically changed the cholesterol metabolism pathway and oxidation-reduction process and depressed gene expression involved in cholesterol efflux and monooxygenase activity. Total antioxidant capacity (T-AOC) positively correlated with Abcg5 and Abcg8. Overall, this study showed the mechanisms underlying hepatotoxicity caused by DEHP, providing new insights into understanding DEHP poisoning., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Tripartite motif (TRIM) family proteins have come forth as important modulators of innate signaling dependent on of E3 ligase activity. Recently, several human TRIM proteins have been identified as unorthodox RNA-binding proteins by RNA interactome analyses; however, their targets and functions remain largely unknown. FTRCA1 is a crucian carp ( Carassius auratus )-specific finTRIM (fish novel TRIM) member and negatively regulates the IFN antiviral response by targeting two retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) pathway molecules, that is, TANK-binding kinase 1 (TBK1) and IFN regulatory factor 7 (IRF7). In this study, we identify FTRCA1 as an RNA-binding E3 ligase and characterize the contribution of its RNA-binding activity and E3 ligase activity to fish IFN response. Besides targeting TBK1 and IRF7, FTRCA1 downregulates fish IFN response also by targeting stimulator of IFN response cGAMP interactor 1 (STING1). E3 ligase activity is required for full inhibition on the TBK1- and IRF7-mediated IFN response, but partial inhibition on the STING1-mediated IFN response. However, FTRCA1 has a general binding potential to mRNAs in vitro, it selectively binds STING1 and IRF7 mRNAs in vivo to attenuate mRNA levels, and it directly interacts with TBK1 protein to target protein degradation for downregulating the IFN response. Our results present an interesting example of a fish species-specific finTRIM protein that has acquired RNA-binding activity and E3 ligase activity to fine-tune fish IFN response., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Recent studies have related the membrane-associated RING-CH-type finger (MARCH) family proteins to host innate immune response. Zebrafish (Danio rerio) MARCH8 is reported to target SVCV glycoprotein for degradation; however, little is known about whether fish MARCH8 is involved in innate interferon (IFN) response. In this study, zebrafish march8 was significantly induced by SVCV infection. Overexpression of MARCH8 diminished fish IFN-mediated antiviral response, thus promoting the replication of SVCV and GCRV in fish cells. Mechanistically, MARCH8 interacts with and degrades MITA and TBK1 proteins to inhibit IFN response. Moreover, MARCH8 has an E3 ligase activity and enhances MITA and TBK1 polyubiquitination. Our findings reveal a mechanism whereby zebrafish MARCH8 downregulates fish IFN response and facilitates viral replication by targeting MITA and TBK1 for protein degradation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Atrial fibrillation (AF) frequently occurs in patients with type 2 diabetes (T2D); however, the longitudinal associations of new-onset AF with risks of adverse health outcomes in patients with T2D remain unclear. In this study, we aimed to determine the associations of new-onset AF with subsequent risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), and mortality among patients with T2D., Research Design and Methods: We included 16,551 adults with T2D, who were free of cardiovascular disease (CVD) and CKD at recruitment from the UK Biobank study. Time-varying Cox regression models were used to assess the associations of incident AF with subsequent risks of incident ASCVD, heart failure, CKD, and mortality., Results: Among the patients with T2D, 1,394 developed AF and 15,157 remained free of AF during the follow-up. Over median follow-up of 10.7-11.0 years, we documented 2,872 cases of ASCVD, 852 heart failure, and 1,548 CKD and 1,776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risk of ASCVD (hazard ratio [HR] 1.85; 95% CI 1.59-2.16), heart failure (HR 4.40; 95% CI 3.67-5.28), CKD (HR 1.68; 95% CI 1.41-2.01), all-cause mortality (HR 2.91; 95% CI 2.53-3.34), and CVD mortality (HR 3.75; 95% CI 2.93-4.80) compared with those without incident AF., Conclusions: Patients with T2D who developed AF had significantly increased risks of developing subsequent adverse cardiovascular events, CKD, and mortality. Our data underscore the importance of strategies of AF prevention to reduce macro- and microvascular complications in patients with T2D., (© 2022 by the American Diabetes Association.)

Blood loss and blood transfusion requirement are important quality control indicators of cardiovascular surgery and cardiovascular anesthesia. Patient blood management (PBM) is an evidence-based, multidisciplinary approach to optimizing the care of patients who may need transfusion, which encompasses anemia management, hemodilution, cell salvage, hemostatic treatment, and other approaches to reducing bleeding and minimizing blood transfusion. PBM in cardiovascular surgery is a "team sport" that involves cardiac and vascular surgeons, anesthesiologists, perfusionist, intensivists, and other health care providers. The current work provides an overview of evidence and practice of PBM at Fuwai Hospital. Implementation of PBM should also take local resource availability and cost-effectiveness of different devices, drugs, technologies, and techniques into consideration.

Three-membered rings (3-rings) are an important structural motif in zeolite chemistry, but their formation remains serendipitous in reticular chemistry when designing zeolitic imidazolate frameworks (ZIFs). Herein, we report a design principle for constructing four new ZIFs, termed ZIF-1001 to -1004, from tetrahedral Zn II centers (T), benzotriazolate (bTZ), and different functionalized benzimidazolates (RbIM) that adopt a new zeolite NPO-type topology built from 3-rings. Two factors were critical for this discovery: i) incorporating the bTZ linker within the structures formed 3-rings due to a ∠(T-bTZ-T) angle of 120-130° reminiscent of the ∠(Ge-O-Ge) angle (130°) observed in germanate zeolite-type structures having 3-rings; and ii) RbIM guided the coordination chemistry of bTZ to bind preferentially in an imidazolate-type mode. This series' ability to selectively capture CO 2 from high-humidity flue gas and trap ethane from tail gas during shale gas extraction was demonstrated., (© 2022 Wiley-VCH GmbH.)

With rapid and non-invasive characteristics, the respiratory route of administration has drawn significant attention compared with the limitations of conventional routes. Respiratory delivery can bypass the physiological barrier to achieve local and systemic disease treatment. A scientometric analysis and review were used to analyze how respiratory delivery can contribute to local and systemic therapy. The literature data obtained from the Web of Science Core Collection database showed an increasing worldwide tendency toward respiratory delivery from 1998 to 2020. Keywords analysis suggested that nasal and pulmonary drug delivery are the leading research topics in respiratory delivery. Based on the results of scientometric analysis, the research hotspots mainly included therapy for central nervous systems (CNS) disorders (Parkinson's disease, Alzheimer's disease, depression, glioblastoma, and epilepsy), tracheal and bronchial or lung diseases (chronic obstructive pulmonary disease, asthma, acute lung injury or respiratory distress syndrome, lung cancer, and idiopathic pulmonary fibrosis), and systemic diseases (diabetes and COVID-19). The study of advanced preparations contained nano drug delivery systems of the respiratory route, drug delivery barriers investigation (blood-brain barrier, BBB), and chitosan-based biomaterials for respiratory delivery. These results provided researchers with future research directions related to respiratory delivery.

Background: A significant proportion of women with preeclampsia (PE) exhibit persistent postpartum hypertension (PHTN) at 3 months postpartum associated with cardiovascular morbidity. This study aimed to screen patients with PE to identify the high-risk population with persistent PHTN., Methods: This retrospective cohort study enrolled 1,000 PE patients with complete parturient and postpartum blood pressure (BP) profiles at 3 months postpartum. The enrolled patients exhibited new-onset hypertension after 20 weeks of pregnancy, while those with PE superimposed upon chronic hypertension were excluded. Latent class cluster analysis (LCCA), a method of unsupervised learning in machine learning, was performed to ascertain maternal exposure clusters from eight variables and 35 subordinate risk factors. Logistic regression was applied to calculate odds ratios (OR) indicating the association between clusters and PHTN., Results: The 1,000 participants were classified into three exposure clusters (subpopulations with similar characteristics) according to persistent PHTN development: high-risk cluster (31.2%), medium-risk cluster (36.8%), and low-risk cluster (32.0%). Among the 1,000 PE patients, a total of 134 (13.4%) were diagnosed with persistent PHTN, while the percentages of persistent PHTN were24.68%, 10.05%, and 6.25% in the high-, medium-, and low-risk clusters, respectively. Persistent PHTN in the high-risk cluster was nearly five times higher (OR, 4.915; 95% confidence interval (CI), 2.92-8.27) and three times (OR, 2.931; 95% CI, 1.91-4.49) than in the low- and medium-risk clusters, respectively. Persistent PHTN did not differ between the medium- and low-risk clusters. Subjects in the high-risk cluster were older and showed higher BP, poorer prenatal organ function, more adverse pregnancy events, and greater medication requirement than the other two groups., Conclusion: Patients with PE can be classified into high-, medium-, and low-risk clusters according to persistent PHTN severity; each cluster has cognizable clinical features. This study's findings stress the importance of controlling persistent PHTN to prevent future cardiovascular disease., (© 2022. The Author(s).)

This study aimed to investigate the association between serum iron (SI) and postoperative delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively analyzed 985 consecutive adult patients diagnosed with aSAH. Demographic, clinical, and laboratory data were recorded. Univariate and multivariate analyses were employed to assess the association between SI and DCI. Propensity-score matching (PSM) analysis was implemented to reduce confounding. Postoperative DCI developed in 14.38% of patients. Lower SI upon admission was detected in aSAH patients with severe clinical conditions and severe aSAH. SI was negatively correlated with WFNS grade (r = −0.3744, p < 0.001) and modified Fisher (mFisher) grade (r = −0.2520, p < 0.001). Multivariable analysis revealed lower SI was independently associated with DCI [odds ratios (OR) 0.281, 95% confidence interval (CI) 0.177−0.448, p < 0.001], while WFNS grade and mFisher grade were not. The receiver-operating characteristics (ROC) curve analysis of SI for DCI gave an area under the curve (AUC) of 0.7 and an optimal cut-off of 7.5 μmol/L (95% CI 0.665 to 0.733, p < 0.0001). PSM demonstrated the DCI group had a significantly lower SI than the non-DCI group (10.91 ± 6.86 vs. 20.34 ± 8.01 μmol/L, p < 0.001). Lower SI remained a significant independent predictor for DCI and an independent poor prognostic factor of aSAH in multivariate analysis (OR 0.363, 95% CI 0.209−0.630, p < 0.001). The predictive performance of SI for poor outcome had a corresponding AUC of 0.718 after PSM. Lower SI upon admission is significantly associated with WFNS grade, mFisher grade, and predicts postoperative DCI and poor outcome at 90 days following aSAH.

Two new clerodane diterpenoids (1 and 2), a new pyran-2-one derivative (3), along with five known compounds (4‒8), were isolated from Croton crassifolius. Notably, crassifolin X (1) is a novel clerodane diterpenoid, characterized with a peculiar δ-lactone core being formed between C-1 and C-4. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (UV, IR, HRESIMS and NMR), and circular dichroism experiments. In addition, all compounds were evaluated for their anti-neuroinflammatory activities based on the expression of TNF-α and IL-6 levels on LPS-induced BV2 cells, and compounds 1‒3 and 5 showed potential anti-neuroinflammatory activity., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Six undescribed abietane-type diterpenoids (tripterydinoids A-F) and five undescribed oleanane-type triterpenoids (tripterytrinoids A-E) were obtained and determined from the stem and branch of Tripterygium wilfordii Hook. f. (Celastraceae). Tripterydinoids A-C possessed the abietane-type diterpenoid skeleton with rare 8, 9-epoxy ring. The structures of undescribed compounds were established by extensive spectroscopic studies [HRESIMS, 1D/2D-NMR and electronic circular dichroism (ECD) calculation]. The absolute configurations of tripterydinoids A, B, E and tripterytrinoid A were defined by X-ray crystallographic analyses. Bioactivity screening indicated that tripterydinoids A-C exhibited potent inhibitory effects against NO release in LPS-activated RAW 264.7 macrophages with IC 50 values of 6.93, 4.46 and 2.98 μM, respectively. Meanwhile, tripterydinoids A-D and tripterytrinoids B, C showed moderate and selective cytotoxicities against five human tumor cell lines (A375, Huh7, MCF-7, HCT-116 and NCI-H460)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: This study was conducted to establish the potential competing endogeneous RNA (ceRNA) network for predicting prognoses in kidney papillary renal cell carcinoma (KIRP) and explore novel therapeutic targets., Methods: The edgeR package in R was used to determine differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), based on data from The Cancer Gene Atlas Program (TCGA) and the Genotype Expression (GTEx) databases. Weighted gene co-expression network analysis (WGCNA) was performed to filter out the mRNAs or lncRNAs that were strongly related to KIRP. The miRNAs that possibly sponged by differentially expressed RNAs lncRNAs (DElncRNAs) were screened using miRcode. Starbase, miRDB, and TargetScan sets were utilized to predict target mRNAs to corresponding miRNAs. LASSO and multivariate Cox regression analyses were applied for the determination of potential prognostic significance. Finally, the lncRNA-miRNA-mRNA ceRNA network was constructed., Results: A total of 1739 DEmRNAs and 1599 DElncRNAs were identified in KIRP. WGCNA analysis suggested that DEmRNAs in the blue module and DElncRNAs in the turquoise module were closely correlated with KIRP. An 8-gene signature was constructed, which had prognostic significance and predictive value in KIRP. Of note, a lncRNA-miRNA-mRNA ceRNA network (including 18 lncRNAs, 5 miRNAs, and 7 mRNAs) was established., Conclusion: This investigation constructed a new lncRNA-miRNA-mRNA ceRNA network, and proposed some genes that may be novel targets, as well as a theoretical basis for the treatment of patients with KIRP.

Aims: China has the largest number of adults with diabetes. Although multiple metabolic risk factors (MRFs) are implicated in the development of diabetes, it remains unclear how they progress during the development of diabetes among Chinese. We examined trajectories of multiple MRFs among Chinese and identified the critical period when drastic changes occurred during the development of diabetes., Methods: This prospective cohort study included participants since 2006-2007 in the Kailuan study. People attended biennial examinations until 2017 with additions of new participants at each examination cycle. The time when a participant first completed the examination was served as the baseline. A total of 122,659 participants without prevalent diabetes at baseline and with complete follow-up data were included. MRFs were collected via biennial physical examinations and laboratory measures. Incident diabetes cases were identified via biennial fasting glucose tests and self-reported physician-diagnosis., Results: During up to 12 years of follow-up, 14,922 incident diabetes cases were identified. Compared with participants who did not develop diabetes, those who developed diabetes had more adverse levels of most MRFs at baseline and during follow-up. Abrupt increases in multiple MRFs (including fasting glucose, surrogate insulin resistance indicators, lipids, systolic blood pressure, pulse pressure, heart rate, alanine aminotransferase, and C-reactive protein) were observed 3 years before the diagnosis of diabetes., Conclusions: We identified 3 years before diabetes diagnosis as a critical period when multiple MRFs experienced drastic changes. This would have implications for early monitoring and timely prevention for individuals who experience sudden adverse progression of multiple MRFs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)