Identification of the hub genes linked to zearalenone-induced hepatotoxicity in broiler chickens.

Zearalenone (ZEN) is a mycotoxin found in food and feed that impairs the function of multiple organs, especially the liver. However, the specific mechanisms through which ZEN induces liver damage in broiler chickens are not well understood. Therefore, this study aimed to identify the key genes linked to the hepatotoxicity induced by ZEN exposure in broiler chickens. Gene expression data from ZEN-treated and control chicken embryo primary hepatocytes (CEPHs) were used to implement differential expression analysis. Totally, 436 differentially expressed genes (DEGs) were detected, in which 223 and 213 genes were up- and down-regulated in ZEN-treated CEPHs, respectively. Gene ontology analysis suggested that these DEGs were involved in various biological processes, including chromosome segregation, mitotic cytokinesis, mitotic cell cycle, cell division, and mitotic spindle organization. Pathway analysis showed that the DEGs were associated with p53, FoxO, ubiquitin-mediated proteolysis, cell cycle, and mismatch repair signaling pathways. Furthermore, the hub genes, including BRCA1, CDC45, CDCA3, CDKN3, CENPE, CENPF, CENPI, CENPM, CENPU, and CEP55, potentially contributed to ZEN-induced hepatotoxicity. In conclusion, our study provides the valuable insight into the mechanism underlying ZEN-induced hepatotoxicity in broiler chickens.

Discovery of LAH-1 as potent c-Met inhibitor for the treatment of non-small cell lung cancer.

ABSTRCTDysregulated HGF/c-Met pathway has been implicated in multiple human cancers and has become an attractive target for cancer intervention. Herein, we report the discovery of N-(3-fluoro-4-((2-(3-hydroxyazetidine-1-carboxamido)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-4-methyl-6-oxo-1,6-dihydropyridazine-3-carboxamide (LAH-1), which demonstrated nanomolar MET kinase activity as well as desirable antiproliferative activity, especially against EBC-1 cells. Mechanism studies confirmed the effects of LAH-1 on modulation of HGF/c-Met pathway, induction of cell apoptosis, inhibition on colony formation as well as cell migration and invasion. In addition, LAH-1 also showed desirable in vitro ADME properties as well as acceptable in vivo PK parameters. The design, synthesis, and characterisation of LAH-1 are described herein.

Identification of novel PD-1/PD-L1 small molecule inhibitors: virtual screening, synthesis and in vitro characterisation.

The PD-1/PD-L1 pathway is considered as one of the most promising immune checkpoints in tumour immunotherapy. However, researchers are faced with the inherent limitations of antibodies, driving them to pursue PD-L1 small molecule inhibitors. Virtual screening followed by experimental validation is a proven approach to discover active compounds. In this study, we employed multistage virtual screening methods to screen multiple compound databases to predict new PD-1/PD-L1 ligands. 35 compounds were proposed by combined analysis of fitness scores, interaction pattern and MM-GBSA binding affinities. Enzymatic assay confirmed that 10 out of 35 ligands were potential PD-L1 inhibitors, with inhibitory rate higher than 50% at the concentration of 30 µM. Among them, ZDS20 was identified as the most effective inhibitor with low micromolar activity (IC50 = 3.27 µM). Altogether, ZDS20 carrying novel scaffold was identified and could serve as a lead for the development of new classes of PD-L1 inhibitors.

WDR54 exerts oncogenic roles in T-cell acute lymphoblastic leukemia.

WDR54 has been recently identified as a novel oncogene in colorectal and bladder cancers. However, the expression and function of WDR54 in T-cell acute lymphoblastic leukemia (T-ALL) were not reported. In this study, we investigated the expression of WDR54 in T-ALL, as well as its function in T-ALL pathogenesis using cell lines and T-ALL xenograft. Bioinformatics analysis indicated high mRNA expression of WDR54 in T-ALL. We further confirmed that the expression of WDR54 was significantly elevated in T-ALL. Depletion of WDR54 dramatically inhibited cell viability and induced apoptosis and cell cycle arrest at S phase in T-ALL cells in vitro. Moreover, knockdown of WDR54 impeded the process of leukemogenesis in a Jurkat xenograft model in vivo. Mechanistically, the expression of PDPK1, phospho-AKT (p-AKT), total AKT, phospho-ERK (p-ERK), Bcl-2 and Bcl-xL were downregulated, while cleaved caspase-3 and cleaved caspase-9 were upregulated in T-ALL cells with WDR54 knockdown. Additionally, RNA-seq analysis indicated that WDR54 might regulate the expression of some oncogenic genes involved in multiple signaling pathways. Taken together, these findings suggest that WDR54 may be involved in the pathogenesis of T-ALL and serve as a potential therapeutic target for the treatment of T-ALL.

Atf4 regulates angiogenic differences between alveolar bone and long bone macrophages by regulating M1 polarization, based on single-cell RNA sequencing, RNA-seq and ATAC-seq analysis.

In the repair of maxillofacial bone defects, autogenous craniofacial bone can often provide superior clinical results over long bone grafts. Most current studies have focused on the osteogenic differences between alveolar bone marrow (ABM) and long bone marrow (LBM), however, studies about the angiogenic differences between the two are currently lacking. We downloaded single-cell RNA sequencing (scRNA-seq) of mouse ABM and LBM respectively from the public database, and the data were processed by using Seurat package. CellphoneDB2 results showed that macrophages had the strongest interaction with mesenchymal stem cells (MSCs) and endothelial cells (ECs). ELISA results confirmed that ABM macrophages secreted a higher level of vascular endothelial growth factor A (Vegfa) compared to LBM macrophages, which further promoted angiogenesis of ECs and MSCs. Using SCENIC package, six key transcription factors (TFs) were identified to regulate the difference between ABM and LBM macrophages, and activating transcription factor 4 (Atf4) was confirmed to be more expressed in ABM macrophages by polymerase chain reaction (PCR) and western blot (WB), with predicted target genes including Vegfa. Besides, the result of scRNA-seq implied ABM macrophages more in M1 status than LBM macrophages, which was confirmed by the following experiments. From the results of another assay for transposase accessible chromatin sequencing (ATAC-seq) and RNA-seq about M1 macrophages, Atf4 was also confirmed to regulate the M1 polarization. So, we suspected that Atf4 regulated the different expression of Vegfa between ABM and LBM macrophages by activating M1 polarization. After knocking down Atf4, the expression of M1 polarization markers and Vegfa were downregulated and vasculogenic differences were eliminated, which were subsequently reversed by the addition of LPS/IFN-γ. Our study might provide a new idea to improve the success rate of autologous bone grafting and treatment of oral diseases.

The impact of previous conservative treatment of atypical hyperplasia on pregnancy outcomes after IVF/ICSI-embryo transfer: a propensity score-matched retrospective cohort study.

STUDY QUESTION: Do women have worse pregnancy and neonatal outcomes of IVF/ICSI-fresh embryo transfer (ET) after conservative treatment of atypical hyperplasia (AH)? SUMMARY ANSWER: AH has no impact on live birth but is associated with increased risks of pregnancy loss and preterm delivery (PTD). WHAT IS KNOWN ALREADY: AH is a precancerous lesion of endometrial cancer. Several recognized AH risk factors include nulliparity, increased body mass index, ovulation disorders, diabetes mellitus, and others. As such, patients are suggested to attempt conception upon achieving AH regression. Recently, successful pregnancies with IVF/ICSI have been increasingly reported. STUDY DESIGN, SIZE, DURATION: Forty-two patients with AH regression and 18 700 women with no evidence of endometrial abnormality, who underwent their first autologous oocytes' retrieval and fresh ET cycles of IVF/ICSI in the Center for Reproductive Medicine, Shandong University, from May 2008 to July 2021, were retrospectively enrolled. PARTICIPANTS/MATERIALS, SETTING, METHODS: First, 42 AH patients were propensity score matched with control women (n = 168) at a 1:4 ratio. Reproductive outcomes and maternal/neonatal complications were compared between the matched pairs. Binary logistic regression analyses were conducted to assess odds ratios (ORs) of AH for live birth, pregnancy loss, and PTD from AH women and all 18 700 eligible controls. MAIN RESULT AND THE ROLE OF CHANCE: Patients with AH achieved a numerically lower live birth rate (LBR) as compared to the matched controls, but without significant difference (26% versus 37%, P = 0.192). However, compared with the matched controls, AH patients showed significantly higher rates of pregnancy loss (52% versus 21%, P = 0.003) and PTD (45% versus 16%, P = 0.041). Further analyses revealed a statistically significantly increased rate of late pregnancy loss (17% versus 3%, P = 0.023), but not early miscarriage (35% versus 18%, P = 0.086), in the AH group. Furthermore, after correcting for potential confounders, the likelihood of a live birth in AH patients narrowly failed to be statistically significantly different from controls (adjusted OR [aOR]: 0.51, 95% CI: 0.25-1.04, P = 0.064). Nonetheless, the logistic regression reconfirmed that AH was an independent risk factor for pregnancy loss (aOR: 3.62, 95% CI: 1.55-8.46, P = 0.003), late pregnancy loss (aOR: 9.33, 95% CI: 3.00-29.02, P < 0.001), and PTD (aOR: 5.70, 95% CI: 1.45-22.38, P = 0.013). LIMITATIONS, REASONS FOR CAUTION: Selection bias was an inherent drawback of this study. First, because of the low AH prevalence among women receiving IVF/ICSI treatment, and consequently, limited sample size, the relationship between AH with LBR and adverse complications might be concealed and underestimated. Hence, the results should be interpreted cautiously. Similarly, the impacts of diverse clinical features of AH patients on the pregnancy outcomes need further studies in a larger population. Second, although most data used in this study were obtained by reviewing the medical records, missing data did exist and so did the recall bias. Third, although the propensity score matching and multivariable logistic models were performed collectively in order to minimize potential confounders between AH and controls, the intrinsic disadvantages of the retrospective nature of this study could not be avoided completely, and additional confirmation bias might be induced with reduplication of statistical analyses. WIDER IMPLICATION OF THE FINDINGS: Our results highlight the necessity of adequate counseling and intensive pregnancy monitoring for AH individuals and their families. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Key Research & Developmental Program of China (2022YFC2703800), the Natural Science Foundation of Shandong Province (ZR2022MH009), and Projects of Medical and Health Technology Development Program in Shandong Province (202005010520, 202005010523). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Scanning-based compressive hyperspectral imaging via spectral-coded illumination.

In this Letter, we present a novel, to the best of our knowledge, scanning-based compressive hyperspectral imaging method via spectral-coded illumination. We achieve efficient and flexible spectral modulation by spectral coding of a dispersive light source while spatial information is obtained by point-wise scanning, which can be applied to optical scanning imaging systems such as lidar. In addition, we propose a new tensor-based joint hyperspectral image reconstruction algorithm that considers spectral correlation and spatial self-similarity to recover three-dimensional hyperspectral data from compressive sampled data. Both simulated and real experiments show that our method has superior performance in visual quality and quantitative analysis.

Altered spontaneous brain activity as a potential imaging biomarker for generalized and focal to bilateral tonic-clonic seizures: A resting-state fMRI study.

OBJECTIVE: We aimed to determine whether alterations in spontaneous regional brain activity in those with generalized tonic-clonic seizures (GTCS) and focal to bilateral tonic-clonic seizures (FBTCS) and explore whether the alterations could be used as biomarkers to classify disease subtypes through support vector machine analysis (SVM). METHODS: The fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) from resting-state functional magnetic resonance imaging (rs-fMRI) data were extracted from 57 patients with GTCS, 35 patients with FBTCS, and 50 age-matched and sex-matched normal controls (NCs) using the DPARSF 5.0 toolbox. Between-group comparisons were adjusted for covariates (age, sex, and equipment). Correlation analyses between imaging biomarkers and the frequency or duration of seizure activity were calculated using partial correlations. The differential imaging indicators, age, and sex were considered as the discriminative features in the SVM to evaluate classification performance. RESULTS: The patients with GTCS showed lower fALFF values (voxel p < 0.001, cluster p < 0.05, Gaussian random field corrected, GRF corrected) in the right postcentral gyrus and precentral gyrus and lower ReHo values (GRF corrected) in the middle temporal gyrus than the NCs. The patients with FBTCS showed higher fALFF (GRF corrected) values in the right postcentral and precentral gyrus and higher ReHo (GRF corrected) values in the right postcentral gyrus. Both fALFF (GRF corrected) and ReHo (GRF corrected) values were lower in the right postcentral gyrus and precentral gyrus in the GTCS group than in the FBTCS group. In patients with FBTCS, fALFF values in the right postcentral and precentral gyrus were positively correlated with duration (r = 0.655, p = 0.008, Bonferroni corrected) in the low-duration group, and ReHo values in the right postcentral gyrus were positively correlated with frequency (r = 0.486, p = 0.022, uncorrected) in the low-frequency group. SVM results showed receiver operating characteristic curves of 0.89, 0.87, and 0.76 for the classification between GTCS and NC, between FBTCS and NC, and GTCS and FBTCS, respectively. SIGNIFICANCE: This study detected alterations in fALFF and ReHo in the postcentral gyrus and precentral gyrus in patients with GTCS and FBTCS, which might contribute to understanding the pathogenesis, disease classification, and clinical targeted therapy.

Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study.

AIM: This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal association between inflammatory bowel disease (IBD) and periodontitis. MATERIALS AND METHODS: We used genetic instruments from the genome-wide association study summary statistics of European descent for IBD (12,882 cases and 21,770 controls) to investigate the association with periodontitis (3046 cases and 195,395 controls) and vice versa. The radial inverse-variance weighted method was carried out to obtain the primary causal estimates, and the robustness of the results was assessed by a series of sensitivity analyses. Due to multiple testing, associations with p values <.008 were considered as statistically significant, and p values ≥.008 and <.05 were considered as suggestively significant. RESULTS: In the primary causal estimates, IBD as a whole was associated with an increased risk of periodontitis (odds ratio [OR], 1.060; 95% confidence interval [CI], 1.017; 1.105; p = .006). Subtype analyses showed that ulcerative colitis (UC) was associated with periodontitis (OR, 1.074; 95% CI 1.029; 1.122; p = .001), while Crohn's disease (CD) was not. Regarding the reverse direction, periodontitis showed a suggestive association with IBD as a whole (OR, 1.065; 95% CI 1.013; 1.119; p = .014). Subtype analyses revealed that periodontitis was associated with CD (OR, 1.100; 95% CI 1.038; 1.167; p = .001) but not UC. The final models after outlier removal showed no obvious pleiotropy, indicating that our primary analysis results were reliable. CONCLUSIONS: The present MR study provides moderate evidence on the bidirectional causal relationship between IBD and periodontitis. The bidirectional increased risk found in our study was marginal and, possibly, of limited clinical relevance. More studies are needed to support the findings of our current study.

Causes of death after testicular cancer diagnosis: a US population-based analysis.

BACKGROUND: After the introduction of cisplatin-based chemotherapy, the survival time of testicular cancer (TC) patients has improved dramatically. However, the overall risk of death in patients with TC remains significantly higher than in the general population. The aim of this study was to assess and quantify the causes of death after TC diagnosis. METHOD: In total, 44,975 men with TC in the United States diagnosed and registered by the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2018 were studied. In this study, standardized mortality rates (SMRs) were calculated for each cause of death in TC individuals and further analyzed in strata according to age and race. RESULT: Of the included participants, 3,573 (7.94%) died during the follow-up period. The greatest proportion of deaths (38.20%) occurred within 1 to 5 years after diagnosis. Most deaths occurred from TC itself and other cancers. For non-malignant conditions, the most common causes of death within 1 years after diagnosis were accidents and adverse effects (53, 4.75%) followed by diseases of heart (45, 4.04%). However, > 1 years after diagnosis, the most common noncancer causes of death were heart diseases. Results of stratified analysis show that non-Hispanic White TC participants have a lower SMR (0.68, 95% CI, 33.39-38.67) from Cerebrovascular Diseases than the general U.S. CONCLUSIONS: Although TC remains the most common cause of death after TC diagnosis, other non-TC causes of death represent a significant number of deaths among TC men. These findings help TC survivors understand the various health risks that may occur at different follow-up periods.

Development and validation of two nomograms for predicting overall survival and Cancer-specific survival in prostate cancer patients with bone metastases: a population-based study.

BACKGROUND: Prostate cancer with bone metastasis has significant invasiveness and markedly poorer prognosis. The purpose of this study is to establish two nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of prostate cancer patients with bone metastasis. METHODS: From January 2000 to December 2018, a total of 2683 prostate adenocarcinoma with bone metastasis patients were identified from the Surveillance, Epidemiology, and End Results Program (SEER) database. These patients were then divided into a training cohort and a validation cohort, with OS and CSS as the study endpoints. Correlation analyses were employed to assess the relationship between variables. Univariate and multivariate Cox analyses were utilized to ascertain the independent prognostic factors. Calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were employed to evaluate discrimination and calibration of the nomogram. DCA was applied to examine accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Lastly, the risk stratifications of the nomogram and the AJCC Stage System were compared. RESULTS: There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that seven variables (age, surgery, brain metastasis, liver metastasis, lung metastasis, Gleason score, marital status) and six variables (age, surgery, lung metastasis, liver metastasis, Gleason score, marital status) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System. CONCLUSION: Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of PABM patients.

Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors.

Inhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3Kα and a panel of PI3Kα-addicted cancer cells. Among them, compound 35 was identified as a PI3Kα inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed 35 induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable in vitro ADME properties. The design, synthesis, and SAR exploration of 35 are described within.

Diversity, Biosynthesis and Bioactivity of Aeruginosins, a Family of Cyanobacteria-Derived Nonribosomal Linear Tetrapeptides.

Aeruginosins, a family of nonribosomal linear tetrapeptides discovered from cyanobacteria and sponges, exhibit in vitro inhibitory activity on various types of serine proteases. This family is characterized by the existence of the 2-carboxy-6-hydroxy-octahydroindole (Choi) moiety occupied at the central position of the tetrapeptide. Aeruginosins have attracted much attention due to their special structures and unique bioactivities. Although many studies on aeruginosins have been published, there has not yet been a comprehensive review that summarizes the diverse research ranging from biogenesis, structural characterization and biosynthesis to bioactivity. In this review, we provide an overview of the source, chemical structure as well as spectrum of bioactivities of aeruginosins. Furthermore, possible opportunities for future research and development of aeruginosins were discussed.

PLFace: Progressive learning for face recognition with mask bias.

The outbreak of the COVID-19 coronavirus epidemic has promoted the development of masked face recognition (MFR). Nevertheless, the performance of regular face recognition is severely compromised when the MFR accuracy is blindly pursued. More facts indicate that MFR should be regarded as a mask bias of face recognition rather than an independent task. To mitigate mask bias, we propose a novel Progressive Learning Loss (PLFace) that achieves a progressive training strategy for deep face recognition to learn balanced performance for masked/mask-free faces recognition based on margin losses. Particularly, our PLFace adaptively adjusts the relative importance of masked and mask-free samples during different training stages. In the early stage of training, PLFace mainly learns the feature representations of mask-free samples. At this time, the regular sample embeddings shrink to the prototype. In the later stage of training, PLFace converges on mask-free samples and further focuses on masked samples until the masked sample embeddings are also gathered in the center of the class. The entire training process emphasizes the paradigm that normal samples shrink first and masked samples gather afterward. Extensive experimental results on popular regular and masked face benchmarks demonstrate the superiority of our PLFace over state-of-the-art competitors.

Multi-Omics Analysis Reveals Intricate Gene Networks Involved in Female Development in Melon.

Sexual differentiation is an important developmental phenomenon in cucurbits that directly affects fruit yield. The natural existence of multiple flower types in melon offers an inclusive structure for studying the molecular basis of sexual differentiation. The current study aimed to identify and characterize the molecular network involved in sex determination and female development in melon. Male and female pools separated by the F2 segregated generation were used for sequencing. The comparative multi-omics data revealed 551 DAPs and 594 DEGs involved in multiple pathways of melon growth and development, and based on functional annotation and enrichment analysis, we summarized four biological process modules, including ethylene biosynthesis, flower organ development, plant hormone signaling, and ubiquitinated protein metabolism, that are related to female development. Furthermore, the detailed analysis of the female developmental regulatory pathway model of ethylene biosynthesis, signal transduction, and target gene regulation identified some important candidates that might have a crucial role in female development. Two CMTs ((cytosine-5)-methyltransferase), one AdoHS (adenosylhomocysteinase), four ACSs (1-aminocyclopropane-1-carboxylic acid synthase), three ACOs (ACC oxidase), two ARFs (auxin response factor), four ARPs (auxin-responsive protein), and six ERFs (Ethylene responsive factor) were identified based on various female developmental regulatory models. Our data offer new and valuable insights into female development and hold the potential to offer a deeper comprehension of sex differentiation mechanisms in melon.

SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner.

BACKGROUND: Renal clear cell carcinoma (ccRCC) is the most prevalent tumors worldwide. Discovering effective biomarkers is essential to monitor the prognosis and provide alternative clinical options. SPTBN1 is implicated in various cancerous processes. However, its role in ccRCC remains unelucidated. This study intends to explore the biological function and mechanism of SPTBN1 in ccRCC. METHODS: Single-cell and bulk RNA-seq, tissue microarray, real-time quantitative PCR, and western blotting were applied to verify the expression and predictive value of SPTBN1 in ccRCC. Gain or loss of functional ccRCC cell line models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Actinomycin D experiment, RNA immunoprecipitation (RIP), specific inhibitors, and rescue experiments were carried out to define the molecular mechanisms. RESULTS: SPTBN1 was down-regulated in ccRCC and knockdown of SPTBN1 displayed a remarkably oncogenic role both in vitro and in vivo; while overexpressing SPTBN1 reversed this effect. SPTBN1 mediated ccRCC progression via the pathway of glutamate pyruvate transaminase 2 (GPT2)-dependent glycolysis. The expression of GPT2 was significantly negatively correlated with that of SPTBN1. As an RNA binding protein SPTBN1, regulated the mRNA stability of GPT2. CONCLUSION: Our research demonstrated that SPTBN1 is significantly down-regulated in ccRCC. SPTBN1 knockdown promotes ccRCC progression via activating GPT2-dependent glycolysis. SPTBN1 may serve as a therapeutic target for the treatment of ccRCC.

Stomatal opening ratio mediates trait coordinating network adaptation to environmental gradients.

A trait coordination network is constructed through intercorrelations of functional traits, which reflect trait-based adaptive strategies. However, little is known about how these networks change across spatial scales, and what drivers and mechanisms mediate this change. This study bridges that gap by integrating functional traits related to plant carbon gain and water economy into the coordination network of Siberian elm (Ulmus pumila), a eurybiont that survives along a 3800 km environmental gradient from humid forest to arid desert. Our results demonstrated that both stomatal density and stomatal size reached a physiological threshold at which adjustments in these traits were not sufficient to cope with the increased environmental stress. Network analysis further revealed that the mechanism for overcoming this threshold, the stomatal opening ratio, gratio , was represented by the highest values for centrality across different spatial scales, and therefore mediated the changes in the trait coordination network along environmental gradients. The mediating roles manifested as creating the highest maximum theoretical stomatal conductance (gsmax ) but lowest possible gratio for pathogen defense in humid regions, while maintaining the gratio 'sweet spot' (c. 20% in this region) for highest water use efficiency in semihumid regions, and having the lowest gsmax and highest gratio for gas exchange and leaf cooling in arid regions. These results suggested that the stomatal traits related to control of stomatal movement play fundamental roles in balancing gas exchange, leaf cooling, embolism resistance and pathogen defense. These insights will allow more accurate model parameterization for different regions, and therefore better predictions of species' responses to global change.

Ileoanal Pouch Syndrome Is Common and Associated With Significant Disability in Patients With Ulcerative Colitis Undergoing IPAA.

BACKGROUND: Recently, ileoanal pouch syndrome (IPS) has been proposed and defined according to a series of patient-centered bowel symptoms and consequences after ileoanal pouch surgery. OBJECTIVE: The purpose of this study was to investigate the prevalence of IPS and the related disability in UC patients undergoing IPAA. DESIGN: This was a cross-sectional study. SETTING: This study was conducted in a tertiary center. PATIENTS: Data of 128 UC-related IPAA from October 2014 to May 2021 were collected. MAIN OUTCOME MEASURES: Primary outcomes were prevalence of IPS. RESULTS: One hundred twenty-eight patients were enrolled with a median postoperative follow-up of 2.64 (IQR, 1.31-3.80) years. The prevalence of IPS and its constituent symptoms and consequences are lower for patients with longer follow-up after ileostomy reversal. Fecal incontinence and pad usage had the greatest impact on the quality of life affecting 29% and 31% of patients. IPS group had a significantly higher IBD-Disability Index score compared to the non-IPS group (27.25 vs 12.15, p < 0.001). Multivariate analysis showed that 4 symptoms (fecal incontinence, clustering, fragmentation and incomplete evacuation, and nocturnal symptoms) and 2 consequences (pad usage and negative mental alterations) were associated with increased IBD-Disability Index (p < 0.05). For patients followed-up for >2 years, multivariate analysis showed that male gender (OR, 4.485; 95% CI, 1.354-14.857; p = 0.014), preoperative duration of disease (OR, 1.013; 95% CI, 1.001-1.025; p = 0.031), and postoperative follow-up (OR, 0.462; 95% CI, 0.244-0.876; p = 0.049) were independently associated with IPS. LIMITATIONS: This is a single-center cross-sectional study rather than a prospective multicenter large longitudinal study. CONCLUSIONS: IPS is a common situation negatively affecting the quality of life for patients with ulcerative colitis undergoing IPAA, and its rate decreased over time from ileal pouch surgery. See Video Abstract at http://links.lww.com/DCR/C41. EL SNDROME DEL RESERVORIO ILEOANAL ES COMN Y EST ASOCIADO CON UNA DISCAPACIDAD SIGNIFICATIVA EN PACIENTES CON CU CON RESERVORIO ILEAL Y ANASTOMOSIS RESERVORIOANAL: ANTECEDENTES:Recientemente se propuso y definió el síndrome del reservorio ileoanal de acuerdo con una serie de síntomas intestinales centrados en el paciente y las consecuencias después de la cirugía del reservorio ileoanal.OBJETIVO:El propósito de este estudio fue investigar la prevalencia del síndrome del reservorio ileoanal y la discapacidad relacionada en pacientes con colitis ulcerosa con reservorio ileal y anastomosis reservorio-anal.DISEÑO:Este fue un estudio transversal.ESCENARIO:Este estudio se realizó en un centro terciario.PACIENTES:Se recopilaron datos de 128 pacientes con reservorio ileal por colitis ulcerosa desde octubre de 2014 hasta mayo de 2021.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la prevalencia del síndrome del reservorio ileoanal.RESULTADOS:Ciento veintiocho pacientes fueron reclutados con una mediana de seguimiento postoperatorio de 2,64 (IQR, 1,31-3,80) años. La prevalencia del síndrome del reservorio ileoanal y sus síntomas y consecuencias constituyentes es menor para los pacientes con un seguimiento más prolongado después de la reversión de la ileostomía. La incontinencia fecal y el uso de compresas tuvieron el mayor impacto en la calidad de vida, afectando al 29% y al 31% de los pacientes. El grupo con síndrome del reservorio ileoanal tuvo una puntuación del índice de discapacidad por enfermedad inflamatoria intestinal significativamente más alta en comparación con el grupo sin síndrome del reservorio ileoanal (27,25 frente a 12,15, p <0,001). El análisis multivariado mostró que 4 síntomas (incontinencia fecal, agrupamiento, fragmentación y evacuación incompleta y síntomas nocturnos) y 2 consecuencias (uso de toallas higiénicas y alteraciones mentales negativas) se asociaron con un aumento del índice de discapacidad por enfermedad inflamatoria intestinal (p <0,05). Para los pacientes seguidos durante más de dos años, el análisis multivariado mostró que el sexo masculino (OR, 4,485; IC 95%, 1,354-14,857; p = 0,014), la duración preoperatoria de la enfermedad (OR, 1,013; IC 95%, 1,001-1,025; p = 0,031) y el seguimiento postoperatorio (OR, 0,462; IC 95%, 0,244-0,876; p = 0,049) se asociaron de forma independiente con el síndrome del reservorio ileoanal.LIMITACIONES:Este es un estudio transversal de un solo centro en lugar de un gran estudio longitudinal prospectivo multicéntrico.CONCLUSIONES:El síndrome del reservorio ileoanal es una situación común que afecta negativamente la calidad de vida de los pacientes con colitis ulcerosa sometidos a anastomosis del reservorio ileal-anal, y su tasa disminuyó con el tiempo a partir de la cirugía del reservorio ileal. El sexo masculino y la mayor duración preoperatoria de la enfermedad son factores de riesgo importantes para el síndrome del reservorio ileoanal. Consulte Video Resumen en http://links.lww.com/DCR/C41. (Traducción-Dr. Felipe Bellolio).

The compensation effect between safety and efficiency in xylem and role in photosynthesis of gymnosperms.

The classical theory of safety-efficiency trade-off is a common theme in plant sciences. Despite safety and efficiency partly compensating for each other physiologically (namely, there is a compensation effect, CE, among traits from the "whole" organism perspective), they are always mathematically described as a trade-off against one another. However, the compensation effect has never been defined and quantified, let alone its role in the xylem water transport and subsequently photosynthesis. Here, we developed an alternative theory to define the CE as a positive relationship between safety and efficiency, and further define a new trade-off index, SETO, that is expressed as CE multiplied by a trade-off factor (differing from the classical average trade-off value). Then, we tested SETO- and CE-photosynthetic rate relationships across different levels based on a common garden experiment using nine conifers and published data for gymnosperms. The results demonstrated that the compensation effect in xylem functions was the dominant force in facilitating photosynthetic rates from species- to phylum-scale. By integrating the compensation effect into the xylem hydraulic functional strategy, our study clearly indicated that the compensation effect is the evolutionary basis for the coordination of xylem hydraulic and photosynthesis physiology.

Association of urinary phthalate metabolites with renal function among 9989 US adults.

PURPOSE: This study aimed to investigate the relationship between phthalate metabolites and renal function. METHODS: We analyzed data from 9989 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Renal function was reflected by estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and hypertension. We used generalized linear regression to estimate the correlation between covariate-adjusted creatinine-normalized phthalate metabolites and renal function. In addition, subgroup analysis was used to further compare the effect differences between various populations. RESULTS: In the adjusted model, we found differential associations between phthalates and plasticizers metabolites and renal function. We found that Mono-benzyl phthalate, Mono-(3-carboxypropyl) phthalate, and Mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with lower eGFR with odds ratios (95% confidence intervals) of 1.38 (1.14, 1.67), 1.30 (1.09, 1.57), and 1.27 (1.04, 1.53). While Mono-ethyl phthalate, Mono-(2-ethyl)-hexyl phthalate, Mono-isononyl phthalate and Mono-isobutyl phthalate were negatively associated with lower eGFR with OR values of 0.79 (0.69, 0.90), 0.64 (0.52, 0.78), 0.65 (0.51, 0.82) and 0.80 (0.63, 1.00), respectively. In addition, we found that Mono(carboxyoctyl) phthalate and Mono-isobutyl phthalate were negatively associated with hypertension with ORs of 0.86 (0.78, 0.96) and 0.84 (0.72, 0.98). But phthalates and plasticizers metabolites were not associated with UACR. CONCLUSION: This study found differences in the effects of phthalates and plasticizers metabolites on kidney function, which may raise concerns about possible changes in kidney function resulting from exposure to current levels of plasticizers.