The impact of cytotoxic therapy on the risk of progression and death in clonal cytopenia(s) of undetermined significance.

Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified CCUS patients by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS. A lower proportion of t-CCUS had hypercellular marrows (17.8% vs. 44.8%, P=0.002) but had higher median bone marrow blast percentages. After a median follow up of 2.2 years, t-CCUS had significantly shorter PFS (1.8 vs. 6.3 years, HR 2.1, P=0.007) and median OS (3.6 years vs. not reached, HR 2.3, P=0.007) compared to CCUS. Univariable and multivariable time-to-event analyses showed that exposure to cytotoxic therapy independently accounted for inferior PFS and OS. Despite the similarities in clinical presentation between CCUS and t-CCUS, we show that exposure to prior cytotoxic therapies was an independent risk-factor for inferior outcomes. This suggests that t-CCUS represents a unique clinical entity that needs more stringent monitoring or earlier intervention strategies.

Metabolic Heterogeneity and Potential Immunotherapeutic Responses Revealed by Single-Cell Transcriptomics of Breast Cancer.

BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.

A multicenter study of the mid-term outcomes of patients with uncomplicated type B aortic dissection after distal porous Talos stent-graft implantation.

OBJECTIVES: The Talos stent-graft has extended length to improve aortic remodeling, and distal porous design to decrease the rate of spinal cord ischemia. This study retrospectively analyzed its mid-term outcomes for uncomplicated type B aortic dissection in a multicenter study. METHODS: The primary safety endpoint was 30-day major adverse events, including all-cause mortality, dissection-related mortality, conversion to open surgery, and device-related adverse events. The primary efficacy endpoint was treatment success at 12 months post-operation, defined as no technical failure or secondary dissection-related reintervention. The survival status of the patients was visualized using the Kaplan-Meier curve. Aortic growth was assessed at four levels, and spinal cord ischemia was evaluated at 12 months. RESULTS: 113 patients participated with a mean age of 54.4 (11.1) years and 71.7% (81/113) were male. The 30-day mortality was 0.9% (1/113), no conversions to open surgery or device-related adverse events were recorded. The 12-month treatment success rate was 99.1% (112/113), with no dissection-related reinterventions. There was no spinal cord or visceral ischemia at 12 months. At a median of 34 months follow-up, 9 further deaths were recorded and the 3-year survival rate was 91.7%. The percentage of aortic growth was 1.8% (2/111) at the tracheal bifurcation, 3.6% (4/111) below the left atrium, 6.0% (5/83) above the celiac artery, and 12.1% (9/74) below the lower renal artery. The total thrombosis rate of the false lumen at the stented segment was 80.5% (91/113). CONCLUSIONS: The results showed satisfactory results of Talos stent-graft in terms of safety and efficacy. More data are needed to confirm the long-term performance.

Assessing Long-Term Neurologic Outcomes in SAMD9L-Related Ataxia-Pancytopenia Syndrome.

BACKGROUND: Most published reports on SAMD9L-related ataxia-pancytopenia syndrome (ATXPC) have emphasized the hematologic findings. Fewer details are known about the progression of neurologic manifestations and methods for monitoring them. CASES: We present six individuals from two families transmitting a heterozygous variant in SAMD9L, exhibiting clinical variations in their hematologic and neurologic findings. Serial motor function testing was used to monitor motor proficiency over a 2 to 3 year period in the proband and his father from Family 1. CONCLUSIONS: Our case series focuses on the neurologic progression in patients with heterozygous variants in SAMD9L. Patients with ATXPC should be followed to evaluate a wide range of neurologic manifestations. Serial motor function testing using a standardized method is helpful to track changes in balance and coordination in children and adults with ATXPC and could aid in a future extended natural history study.

Atomically Precise Nanometer-Sized Pt Catalysts with an Additional Photothermy Functionality.

Atomically precise ~1-nm Pt nanoparticles (nanoclusters, NCs) with ambient stability are important in fundamental research and exhibit diverse practical applications (catalysis, biomedicine, etc.). However, synthesizing such materials is challenging. Herein, by employing the mixture ligand protecting strategy, we successfully synthesized the largest organic-ligand-protected (~1-nm) Pt23 NCs precisely characterized with mass spectrometry and single-crystal X-ray diffraction analyses. Interestingly, natural population analysis and Bader charge calculation indicate an alternate, varying charge -layer distribution in the sandwich-like Pt23 NC kernel. Pt23 NCs can catalyze the oxygen reduction reaction under acidic conditions without requiring calcination and other treatments, and the resulting specific and mass activities without further treatment are sevenfold and eightfold higher than those observed for commercial Pt/C catalysts, respectively. Density functional theory and d-band center calculations interpret the high activity. Furthermore, Pt23 NCs exhibit a photothermal conversion efficiency of 68.4% under 532-nm laser irradiation and can be used at least for six cycles, thus demonstrating great potential for practical applications.

Japanese encephalitis virus E protein domain III immunization mediates cross-protection against Zika virus in mice via antibodies and CD8+ T cells.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are antigenically related flaviviruses that co-circulate in many countries/territories. The interaction between the two viruses needs to be determined. Recent findings by ourselves and other labs showed that JEV-elicited antibodies (Abs) and CD8+ T cells exacerbate and protect against subsequent ZIKV infection, respectively. However, the impact of JEV envelope (E) protein domain III (EDIII)-induced immune responses on ZIKV infection is unclear. We show here that sera from JEV-EDIII-vaccinated mice cross-react with ZIKV-EDIII in vitro, and transfer of the same sera to mice significantly decreases death upon lethal ZIKV infection at a dose-dependent manner. Maternally acquired anti-JEV-EDIII Abs also significantly reduce the mortality of neonatal mice born to JEV-EDIII-immune mothers post ZIKV challenge. Similarly, transfer of ZIKV-EDIII-reactive IgG purified from JEV-vaccinated humans increases the survival of ZIKV-infected mice. Notably, transfer of an extremely low volume of JEV-EDIII-immune sera or ZIKV-EDIII-reactive IgG does not mediate the Ab-mediated enhancement (ADE) of ZIKV infection. Similarly, transfer of JEV-EDIII-elicited CD8+ T cells protects recipient mice against ZIKV challenge. These results demonstrate that JEV-EDIII-induced immune components including Abs and T cells have protective roles in ZIKV infection, suggesting EDIII is a promising immunogen for developing effective and safety JEV vaccine.

Study on the hemodynamic effects of different pulsatile working modes of a rotary blood pump using a microfluidic platform that realizes in vitro cell culture effectively.

Rotary blood pumps (RBPs) operating at a constant speed generate non-physiologic blood pressure and flow rate, which can cause endothelial dysfunction, leading to adverse clinical events in peripheral blood vessels and other organs. Notably, pulsatile working modes of the RBP can increase vascular pulsatility to improve arterial endothelial function. However, the laws and related mechanisms of differentially regulating arterial endothelial function under different pulsatile working modes are still unclear. This knowledge gap hinders the optimal selection of the RBP working modes. To address these issues, this study developed a multi-element in vitro endothelial cell culture system (ECCS), which could realize in vitro cell culture effectively and accurately reproduce blood pressure, shear stress, and circumferential strain in the arterial endothelial microenvironment. Performance of this proposed ECCS was validated with numerical simulation and flow experiments. Subsequently, this study investigated the effects of four different pulsation frequency modes that change once every 1-4-fold cardiac cycles (80, 40, 80/3, and 20 cycles per min, respectively) of the RBP on the expression of nitric oxide (NO) and reactive oxygen species (ROS) in endothelial cells. Results indicated that the 2-fold and 3-fold cardiac cycles significantly increased the production of NO and prevented the excessive generation of ROS, potentially minimizing the occurrence of endothelial dysfunction and related adverse events during the RBP support, and were consistent with animal study findings. In general, this study may provide a scientific basis for the optimal selection of the RBP working modes and potential treatment options for heart failure.

Boosting Enzyme Activity in Enzyme Metal-Organic Framework Composites.

Enzymes, as highly efficient biocatalysts, excel in catalyzing diverse reactions with exceptional activity and selective properties under mild conditions. Nonetheless, their broad applications are hindered by their inherent fragility, including low thermal stability, limited pH tolerance, and sensitivity to organic solvents and denaturants. Encapsulating enzymes within metal-organic frameworks (MOFs) can protect them from denaturation in these harsh environments. However, this often leads to a compromised enzyme activity. In recent years, extensive research efforts have been dedicated to enhancing enzymatic activity within MOFs, leading to the development of new enzyme-MOF composites that not only preserve their catalytic potential but also outperform their free counterparts. This Review provides a comprehensive review on recent developments in enzyme-MOF composites with a specific emphasis on their enhanced enzymatic activity compared to free enzymes.

Feasibility of Ultrasound-Guided Percutaneous Axillary Artery Cannulation for Veno-Arterial Extracorporeal Membrane Oxygenation and its Effect on the Recovery of Spontaneous Heartbeat in Patients with ECPR.

Objective: The measurement of the right and left axillary arteries and aortic arch and their vessels by multi-row spiral CT angiography provides the basis for clinical catheter selection and depth for axillary artery placement. This study reported the clinical experience of 7 patients who successfully underwent ultrasound-guided percutaneous axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: Patients who had CT angiography of the thoracic aorta at our institution between January 2020 and March 2022 were assessed for eligibility and included. The diameters of the cephalic trunk (D1), right common carotid artery (D2), right axillary artery (D3), left common carotid artery (D4), left axillary artery opening (D5), right axillary artery cannulation length (L1), and left axillary artery cannulation length (L2) were measured. The tangential angles α, ß, and γ of the cephalic trunk, left common carotid artery and left subclavian and aorta was measured using an automatic angle-forming tool. The decision to use a 15F cannula for ultrasound-guided percutaneous axillary artery cannulation in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) aims to achieve optimal vascular access. This cannula size strikes a balance, providing sufficient blood flow rates for ECMO support while minimizing the risk of complications associated with larger cannulas. Precise measurements of arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries, play a crucial role in guiding catheter selection and determining the depth of axillary artery placement. These measurements allow for tailored approaches based on individual patient characteristics, enhancing the safety and efficacy of the intervention. Additionally, measuring tangential angles (α, ß, and γ) provides insights into arterial alignment, optimizing the cannula trajectory for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy, minimizing complications, and ensuring the success of ultrasound-guided percutaneous axillary artery cannulation. In summary, the choice of a 15F cannula and precise measurements are essential components of the methodology, emphasizing safety, efficacy, and personalized approaches in VA-ECMO. From March to June 2022, 7 patients (6 males and 1 female) in our intensive care medicine department underwent successful ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with 15F cannula, including 3 cases with extracorporeal cardiopulmonary resuscitation (ECPR) and 4 cases with circulatory collapse. Results: 292 patients met the study criteria, 215 males and 77 females, with a mean age of 67.2±14.2 years. The measurements showed that D1 was (13.1±2.0) mm, D2 was (8.8±2.5) mm, D3 was (6.1±1.2) mm, D4 was (8.3±3.5) mm, D5 was (6.1±1.1) mm, L1 was (114.1±17.8) mm, and L2 was (128.4±20.2) mm. The tangential angles α of the cephalic trunk left common carotid artery and left subclavian artery to the aorta were (43.8°±17.1°), ß was (50.7°±14.8°), and γ was (62.4°±19.1°). Males had significantly wider D3 and D5, longer L1 and L2, and smaller gamma angles than females (P < .05). Three ECPR cases showed no recovery of the spontaneous heartbeat with femoral artery cannulation for VA-ECMO but recovered spontaneous heartbeat after axillary artery cannulation for VA-ECMO was adopted. The measurements in this study have important implications for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) procedures. They provide crucial information about arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries. This information guides clinicians in selecting catheters and determining the ideal depth for percutaneous axillary artery cannulation during ECMO interventions. Notable gender differences in arterial dimensions highlight the need for personalized approaches in ECMO procedures. Customizing catheter choices and cannulation depth based on individual patient characteristics, informed by these measurements, improves the safety and effectiveness of the intervention. The measured tangential angles (α, ß, and γ) offer insights into arterial alignment, crucial for optimizing cannula trajectory and ensuring proper alignment for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy and minimizing the risk of complications during ECMO procedures. In summary, these measurements directly enhance the precision and safety of VA-ECMO procedures, underscoring the importance of personalized approaches based on individual anatomical variations and improving overall intervention success and outcomes. Conclusion: Ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with a 15F cannula is clinically feasible. Axillary artery cannulation for VA-ECMO contributes to the restoration of spontaneous heartbeat in ECPR patients more than femoral artery cannulation, and the possible mechanism is a better improvement of coronary blood flow. However, the study has limitations, including a modest sample size and a single-center, retrospective design, impacting its generalizability. To validate and extend these findings, further research with larger and diverse cohorts, including prospective investigations, is necessary to ensure their applicability across various clinical settings and patient demographics in VA-ECMO.

Insufficient secretion of pancreatic FGF21 is the toxicological mechanism and therapeutic target of asparaginase-associated pancreatitis.

Asparaginase-associated pancreatitis (AAP) is a severe and potentially life-threatening drug-induced pancreas targeted toxicity in the combined chemotherapy of acute lymphoblastic leukemia among children and adolescents. The toxicological mechanism of AAP is not yet clear, and there are no effective preventive and treatment measures available clinically. Fibroblast growth factor 21 (FGF21) is a secretory hormone that regulates lipid, glucose, and energy metabolism balance. Acinar tissue is the main source of pancreatic FGF21 protein and plays an important role in maintaining pancreatic metabolic balance. In this study, we found that the decrease of FGF21 in pancreas is closely related to AAP. Pegaspargase (1 IU/g) induces widespread edema and inflammatory infiltration in the pancreas of rats/mice. The specific expression of FGF21 in the acinar tissue of AAP rats was significantly downregulated. Asparaginase caused dysregulation of the ATF4/ATF3/FGF21 axis in acinar tissue or cells, and thus mediated the decrease of FGF21. It greatly activated ATF3 in the acinar, which competed with ATF4 for the Fgf21 promoter, thereby inhibiting the expression of FGF21. Pharmacological replacement of FGF21 (1 mg/kg) or PERK inhibitors (GSK2656157, 25 mg/kg) can significantly mitigate the pancreatic tissue damage and reduce markers of inflammation associated with AAP, representing potential strategies for the prevention and treatment of AAP.

Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements.

The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

Multi-omics analysis provides new insights into the changes of important nutrients and fructose metabolism in loquat bud sport mutant.

Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat.

Establishment of animal models and behavioral studies for autism spectrum disorders.

In recent years, the incidence of autism spectrum disorder (ASD) has increased, but the etiology and pathogenesis remain unclear. In this narrative review, we review and systematically summarize the methods used to construct animal models to study ASD and the related behavioral studies based on recent literature. Utilization of various ASD animal models can complement research on the etiology, pathogenesis, and core behaviors of ASD, providing information and a foundation for further basic research and clinical treatment of ASD.

Hydrazone Phosphaketene as a Synthetic Platform To Obtain Three Classes of 1,2,4-Diazaphosphol Derivatives by Switchable Chemoselectivity Strategies.

We introduce switchable chemoselectivity strategies based on the hydrazone phosphaketene intermediate to synthesize three classes of 1,2,4-diazaphosphol derivatives. First, the five-membered heterocyclic P and O anion intermediates acted as nucleophilic agents in the selective construction of C-P and C-O bonds. Second, the phosphinidene served as a phosphorus synthon, allowing for the formation of C-P and C-N bonds. Finally, a stepwise mechanism, supported by DFT calculations, was invoked to explain the reaction selectivity.

Representativeness of the PIONEER-HF and PARAGLIDE-HF in patients hospitalized with acute heart failure.

AIMS: The PIONEER-HF and PARAGLIDE-HF trials aimed to determine the efficacy and safety of the in-hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real-world routine care is unclear. This study aimed to investigate the applicability of the PIONEER-HF and PARAGLIDE-HF trials to real-world AHF patients. METHODS AND RESULTS: We identified 28 293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER-HF eligible (n = 3683) and non-eligible (n = 3502) patients with an LVEF ≤40%, and PARAGLIDE-HF eligible (n = 5191) and non-eligible (n = 5832) patients with an LVEF >40%. Over a mean follow-up of 3.5 years, the PIONEER-HF non-eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88-1.04). No significant difference was found in the composite outcome between PARAGLIDE-HF non-eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90-1.04). CONCLUSIONS: Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril-valsartan. Yet, non-eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril-valsartan benefits in non-eligible AHF patients.

Early gastric cancer detection and lesion segmentation based on deep learning and gastroscopic images.

Gastric cancer is a highly prevalent disease that poses a serious threat to public health. In clinical practice, gastroscopy is frequently used by medical practitioners to screen for gastric cancer. However, the symptoms of gastric cancer at different stages of advancement vary significantly, particularly in the case of early gastric cancer (EGC). The manifestations of EGC are often indistinct, leading to a detection rate of less than 10%. In recent years, researchers have focused on leveraging deep learning algorithms to assist medical professionals in detecting EGC and thereby improve detection rates. To enhance the ability of deep learning to detect EGC and segment lesions in gastroscopic images, an Improved Mask R-CNN (IMR-CNN) model was proposed. This model incorporates a "Bi-directional feature extraction and fusion module" and a "Purification module for feature channel and space" based on the Mask R-CNN (MR-CNN). Our study includes a dataset of 1120 images of EGC for training and validation of the models. The experimental results indicate that the IMR-CNN model outperforms the original MR-CNN model, with Precision, Recall, Accuracy, Specificity and F1-Score values of 92.9%, 95.3%, 93.9%, 92.5% and 94.1%, respectively. Therefore, our proposed IMR-CNN model has superior detection and lesion segmentation capabilities and can effectively aid doctors in diagnosing EGC from gastroscopic images.

Determining Structures of Layer-by-Layer Spin-Coated Zinc Dicarboxylate-Based Metal-Organic Thin Films.

Thin films of crystalline solids with substantial free volume from organic chromophores and metal secondary building units (SBUs) are promising for engineering new optoelectronic properties through control of interchromophore coupling. Zn-based SBUs are especially relevant in this case because they avoid quenching the chromophore's luminescence. We find that layer-by-layer spin-coating using Zn acetate dihydrate and benzene-1,4-dicarboxylic acid (H2BDC) and biphenyl-4,4'-dicarboxylic acid (H2BPDC) linkers easily produces crystalline thin films. However, analysis of the grazing-incidence wide-angle X-ray scattering (GIWAXS) data reveals the structures of these films vary significantly with the linker, and metal-to-linker molar ratio used for fabrication. Under equimolar conditions, H2BPDC creates a type of structure like that proposed for SURMOF-2, whereas H2BDC generates a different metal-hydroxide-organic framework. Large excess of Zn2+ ions causes the growth of layered zinc hydroxides, irrespective of the linker used. Density functional theory (DFT) calculations provide structural models with minimum total energy that are consistent with the experimentally observed diffractograms. In the broader sense, this work illustrates the importance in this field of careful structural determination, e.g., by utilizing GIWAXS and DFT simulations to determine the structure of the obtained crystalline metal-organic thin films, so properties can be rationally engineered and explained.

Performance, kinetic characteristics and bacterial community of short-cut nitrification and denitrification system at different ferrous ion conditions.

In order to explore the operation performance, kinetic characteristics and bacterial community of the short-cut nitrification and denitrification (SND) system, the SND system with pre-cultured short cut nitrification and denitrification sludge was established and operated under different ferrous ion (Fe (II)) conditions. Experimental results showed that the average NH4+-N removal efficiency (ARE) of SND system was 97.3% on Day 5 and maintained a high level of 94.9% ± 1.3% for a long operation period. When the influent Fe(II) concentration increased from 2.3 to 7.3 mg L-1, the sedimentation performance, sludge concentration and organic matter removal performance were improved. However, higher Fe(II) of 12.3 mg L-1 decreased the removal of nitrogen and CODCr with the relative abundance (RA) of Proteobacteria and Bacteroidetes decreased to 30.28% and 19.41%, respectively. Proteobacteria, Bacteroidetes and Firmicutes were the dominant phyla in SND system. Higher Fe(II) level of 12.3 mg L-1 increase the RA of denitrifying genus Trichococcus (33.93%), and the denitrifying genus Thauera and Tolumonas dominant at Fe(II) level of no more than 7.3 mg L-1.

Mendelian randomization study supports positive bidirectional causal relationships between genetically predicted insomnia symptom and liability to benign prostatic hyperplasia.

BACKGROUND: Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. METHODS: Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran's Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. RESULTS: Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003-1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096-2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. CONCLUSION: This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.