Maternal Brown Rice Diet during Pregnancy Promotes Adipose Tissue Browning in Offspring via Reprogramming PKA Signaling and DNA Methylation.

SCOPE: Brown rice, the most consumed food worldwide, has been shown to possess beneficial effects on the prevention of metabolic diseases. However, the way in which maternal brown rice diet improves metabolism in offspring and the regulatory mechanisms remains unclear. The study explores the epigenetic regulation of offspring energy metabolic homeostasis by maternal brown rice diet during pregnancy. METHODS AND RESULTS: Female mice are fed brown rice during pregnancy, and then body phenotypes, the histopathological analysis, and adipose tissues biochemistry assay of offspring mice are detected. It is found that maternal brown rice diet significantly reduces body weight and fat mass, increases energy expenditure and heat production in offspring. Maternal brown rice diet increases uncoupling protein 1 (UCP1) protein level and upregulates the mRNA expression of thermogenic genes in adipose tissues. Mechanistically, protein kinase A (PKA) signaling is likely responsible in the induced thermogenic program in offspring adipocytes, and the progeny adipocytes browning program is altered due to decreased level of DNA methyltransferase 1 protein and hypomethylation of the transcriptional coregulator positive regulatory domain containing 16 (PRDM16). CONCLUSIONS: These findings demonstrate that maternal brown rice during pregnancy improves offspring mice metabolic homeostasis via promoting adipose browning, and its mechanisms may be mediated by DNA methylation reprogramming.

Adaptive functions of structural variants in human brain development.

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.

5-Heptadecylresorcinol Improves Aging-Associated Hepatic Fatty Acid Oxidation Dysfunction via Regulating Adipose Sirtuin 3.

Aging-associated hepatic fatty acid (FA) oxidation dysfunction contributes to impaired adaptive thermogenesis. 5-Heptadecylresorcinol (AR-C17) is a prominent functional component of whole wheat and rye, and has been demonstrated to improve the thermogenic capacity of aged mice via the regulation of Sirt3. However, the effect of AR-C17 on aging-associated hepatic FA oxidation dysfunction remains unclear. Here, 18-month-old C57BL/6J mice were orally administered with AR-C17 at a dose of 150 mg/kg/day for 8 weeks. Systemic glucose and lipid metabolism, hepatic FA oxidation, and the lipolysis of white adipose tissues (WAT) were measured. The results showed that AR-C17 improved the hepatic FA oxidation, and especially acylcarnitine metabolism, of aged mice during cold stimulation, with the enhancement of systemic glucose and lipid metabolism. Meanwhile, AR-C17 improved the WAT lipolysis of aged mice, promoting hepatic acylcarnitine production. Furthermore, the adipose-specific Sirt3 knockout mice were used to investigate and verify the regulation mechanism of AR-C17 on aging-associated hepatic FA oxidation dysfunction. The results showed that AR-C17 failed to improve the WAT lipolysis and hepatic FA oxidation of aged mice in the absence of adipose Sirt3, indicating that AR-C17 might indirectly influence hepatic FA oxidation via regulating WAT Sirt3. Our findings suggest that AR-C17 might improve aging-associated hepatic FA oxidation dysfunction via regulating adipose Sirt3.

Elevating the significance of legume intake: A novel strategy to counter aging-related mitochondrial dysfunction and physical decline.

Mitochondrial dysfunction increasingly becomes a target for promoting healthy aging and longevity. The dysfunction of mitochondria with age ultimately leads to a decline in physical functions. Among them, biogenesis dysfunction and the imbalances in the metabolism of reactive oxygen species and mitochondria as signaling organelles in the aging process have aroused our attention. Dietary intervention in mitochondrial dysfunction and physical decline during aging processes is essential, and greater attention should be directed toward healthful legume intake. Legumes are constantly under investigation for their nutritional and bioactive properties, and their consumption may yield antiaging and mitochondria-protecting benefits. This review summarizes mitochondrial dysfunction with age, discusses the benefits of legumes on mitochondrial function, and introduces the potential role of legumes in managing aging-related physical decline. Additionally, it reveals the benefits of legume intake for the elderly and offers a viable approach to developing legume-based functional food.

Regioselective hydroformylation of propene catalysed by rhodium-zeolite.

Hydroformylation is an industrial process for the production of aldehydes from alkenes1,2. Regioselective hydroformylation of propene to high-value n-butanal is particularly important, owing to a wide range of bulk applications of n-butanal in the manufacture of various necessities in human daily life3. Supported rhodium (Rh) hydroformylation catalysts, which often excel in catalyst recyclability, ease of separation and adaptability for continuous-flow processes, have been greatly exploited4. Nonetheless, they usually consist of rotationally flexible and sterically unconstrained Rh hydride dicarbonyl centres, only affording limited regioselectivity to n-butanal5-8. Here we show that proper encapsulation of Rh species comprising Rh(I)-gem-dicarbonyl centres within a MEL zeolite framework allows the breaking of the above model. The optimized catalyst exhibits more than 99% regioselectivity to n-butanal and more than 99% selectivity to aldehydes at a product formation turnover frequency (TOF) of 6,500 h-1, surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far. Our comprehensive studies show that the zeolite framework can act as a scaffold to steer the reaction pathway of the intermediates confined in the space between the zeolite framework and Rh centres towards the exclusive formation of n-butanal.

The effect and mechanism of liraglutide on the biological functions of BMSCs in diabetic patients.

OBJECTIVES: To investigate the effect of liraglutide on osteogenesis in human alveolar bone marrow mesenchymal stem cells (BMSCs) and the influence of liraglutide on implant-bone integration in rats with T2DM. SUBJECTS AND METHODS: Extracting BMSCs from the alveoli of diabetic patients treated with insulin. BMSCs were treated with different concentrations of liraglutide. Osteogenesis and the underlying mechanism were investigated via ALP detection, ALP staining, Alizarin Red S staining, Western blotting, and RT-PCR. Liraglutide was given to Wistar and GK rats after implantation, and new bone formation around the implants was analyzed via micro-CT. Implant-bone integration in rats was investigated via toluidine blue staining. RESULTS: Liraglutide enhanced osteogenesis in BMSCs via the BMP2/Smad/Runx2 signaling pathway. The optimal concentration of liraglutide that promoted osteogenesis was 10-8 mol/L. At concentrations higher than 10-7 mol/L, liraglutide had a negative effect on BMSCs. At a concentration of 10-8 mol/L liraglutide, BMSCs and diabetes mellitus-bone marrow stromal cells (DM-BMSCs) showed optimal osteogenesis. Liraglutide promoted implant-bone integration and new bone formation in Wistar and GK rats. CONCLUSIONS: Liraglutide not only promotes osteogenesis of BMSCs in normoglycemic individuals but also enhances osteogenesis of BMSCs in diabetic patients treated with insulin and enhances osseointegration in rats.

ZX703: A Small-Molecule Degrader of GPX4 Inducing Ferroptosis in Human Cancer Cells.

Ferroptosis is a novel form of oxidative cell death triggered by iron-dependent lipid peroxidation. The induction of ferroptosis presents an attractive therapeutic strategy for human diseases, such as prostate cancer and breast cancer. Herein, we describe our design, synthesis, and biological evaluation of endogenous glutathione peroxidase 4 (GPX4) degraders using the proteolysis targeting chimera (PROTAC) approach with the aim of inducing ferroptosis in cancer cells. Our efforts led to the discovery of compound 5i (ZX703), which significantly degraded GPX4 through the ubiquitin-proteasome and the autophagy-lysosome pathways in a dose- and time-dependent manner. Moreover, 5i was found to induce the accumulation of lipid reactive oxygen species (ROS) in HT1080 cells, thereby inducing ferroptosis. This study provides an attractive intervention strategy for ferroptosis-related diseases.

The effect of trisomic chromosomes on spatial genome organization and global transcription in embryonic stem cells.

Aneuploidy frequently occurs in cancer and developmental diseases such as Down syndrome, with its functional consequences implicated in dosage effects on gene expression and global perturbation of stress response and cell proliferation pathways. However, how aneuploidy affects spatial genome organization remains less understood. In this study, we addressed this question by utilizing the previously established isogenic wild-type (WT) and trisomic mouse embryonic stem cells (mESCs). We employed a combination of Hi-C, RNA-seq, chromosome painting and nascent RNA imaging technologies to compare the spatial genome structures and gene transcription among these cells. We found that trisomy has little effect on spatial genome organization at the level of A/B compartment or topologically associating domain (TAD). Inter-chromosomal interactions are associated with chromosome regions with high gene density, active histone modifications and high transcription levels, which are confirmed by imaging. Imaging also revealed contracted chromosome volume and weakened transcriptional activity for trisomic chromosomes, suggesting potential implications for the transcriptional output of these chromosomes. Our data resources and findings may contribute to a better understanding of the consequences of aneuploidy from the angle of spatial genome organization.

Regulation mechanism of EBV-encoded EBER1 and LMP2A on YAP1 and the impact of YAP1 on the EBV infection status in EBV-associated gastric carcinoma.

This study aims to explore the role and regulatory mechanism of Yes-associated protein 1 (YAP1) in the development of Epstein-Barr virus-associated gastric cancer (EBVaGC). Here we showed that EBV can upregulate the expression and activity of YAP1 protein through its encoded latent products EBV-encoded small RNA 1 (EBER1) and latent membrane protein 2A (LMP2A), enhancing the malignant characteristics of EBVaGC cells. In addition, we also showed that overexpression of YAP1 induced the expression of EBV encoding latent and lytic phase genes and proteins in the epithelial cell line AGS-EBV infected with EBV, and increased the copy number of the EBV genome, while loss of YAP1 expression reduced the aforementioned indicators. Moreover, we found that YAP1 enhanced EBV lytic reactivation induced by two known activators, 12-O-tetradecanoylhorbol-13-acetate (TPA) and sodium butyrate (NaB). These results indicated a bidirectional regulatory mechanism between EBV and YAP1 proteins, providing new experimental evidence for further understanding the regulation of EBV infection patterns and carcinogenic mechanisms in gastric cancer.

Bifunctional Electrocatalysts for Overall and Hybrid Water Splitting.

Electrocatalytic water splitting driven by renewable electricity has been recognized as a promising approach for green hydrogen production. Different from conventional strategies in developing electrocatalysts for the two half-reactions of water splitting (e.g., the hydrogen and oxygen evolution reactions, HER and OER) separately, there has been a growing interest in designing and developing bifunctional electrocatalysts, which are able to catalyze both the HER and OER. In addition, considering the high overpotentials required for OER while limited value of the produced oxygen, there is another rapidly growing interest in exploring alternative oxidation reactions to replace OER for hybrid water splitting toward energy-efficient hydrogen generation. This Review begins with an introduction on the fundamental aspects of water splitting, followed by a thorough discussion on various physicochemical characterization techniques that are frequently employed in probing the active sites, with an emphasis on the reconstruction of bifunctional electrocatalysts during redox electrolysis. The design, synthesis, and performance of diverse bifunctional electrocatalysts based on noble metals, nonprecious metals, and metal-free nanocarbons, for overall water splitting in acidic and alkaline electrolytes, are thoroughly summarized and compared. Next, their application toward hybrid water splitting is also presented, wherein the alternative anodic reactions include sacrificing agents oxidation, pollutants oxidative degradation, and organics oxidative upgrading. Finally, a concise statement on the current challenges and future opportunities of bifunctional electrocatalysts for both overall and hybrid water splitting is presented in the hope of guiding future endeavors in the quest for energy-efficient and sustainable green hydrogen production.

Pt,P-codoped carbon nitride nanoenzymes for fluorescence and colorimetric dual-mode detection of cholesterol.

Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.

HMOX1 regulates ferroptosis via mic14 and its impact on chemotherapy resistance in small-cell lung cancer.

This study aimed to investigate the role and molecular mechanism of heme oxygenase-1 (HMOX1) in chemotherapy resistance in small-cell lung cancer (SCLC). Employed bioinformatics, qPCR, and Western Blot to assess HMOX1 levels in SCLC versus normal tissues and its prognostic relevance. CCK-8, flow cytometry, and thiobarbituric acid assays determined HMOX1's impact on SCLC chemosensitivity, ferroptosis markers, lipid peroxidation, and mic14's role in chemoresistance. In the GSE40275 and GSE60052 cohorts, HMOX1 expression was downregulated in SCLC tissues compared to normal tissues. Higher HMOX1 expression was associated with improved prognosis in the Sun Yat-sen University Cancer Hospital cohort and GSE60052 cohort. The RNA and protein levels of HMOX1 were reduced in drug-resistant SCLC cell lines compared to chemosensitive cell lines. Upregulation of HMOX1 increased chemosensitivity and reduced drug resistance in SCLC, while downregulation of HMOX1 decreased chemosensitivity and increased drug resistance. Upregulation of HMOX1 elevated the expression of ferroptosis-related proteins ACSL4, CD71, Transferrin, Ferritin Heavy Chain, and Ferritin Light Chain, while decreasing the expression of GPX4 and xCT. Conversely, downregulation of HMOX1 decreased the expression of ACSL4, CD71, Transferrin, Ferritin Heavy Chain, and Ferritin Light Chain, while increasing the expression of GPX4 and xCT. Upregulation of HMOX1 promoted cellular lipid peroxidation, whereas downregulation of HMOX1 inhibited cellular lipid peroxidation. Upregulation of HMOX1 reduced the RNA level of mic14, while downregulation of HMOX1 increased the RNA level of mic14. mic14 exhibited inhibitory effects on cellular lipid peroxidation in SCLC cells and contributed to reduced chemosensitivity and increased drug resistance in chemoresistant SCLC cell lines. HMOX1 plays a role in ferroptosis by regulating mic14 expression, thereby reversing chemoresistance in SCLC.

Electrocatalytic Hydrogenation Using Palladium Membrane Reactors.

Hydrogenation is a crucial chemical process employed in a myriad of industries, often facilitated by metals such as Pd, Pt, and Ni as catalysts. Traditional thermocatalytic hydrogenation usually necessitates high temperature and elevated pressure, making the process energy intensive. Electrocatalytic hydrogenation offers an alternative but suffers from issues such as competing H2 evolution, electrolyte separation, and limited solvent selection. This Perspective introduces the evolution and advantages of the electrocatalytic Pd membrane reactor (ePMR) as a solution to these challenges. ePMR utilizes a Pd membrane to physically separate the electrochemical chamber from the hydrogenation chamber, permitting the use of water as the hydrogen source and eliminating the need for H2 gas. This setup allows for greater control over reaction conditions, such as solvent and electrolyte selection, while mitigating issues such as low Faradaic efficiency and complex product separation. Several representative hydrogenation reactions (e.g., hydrogenation of C=C, C≡C, C=O, C≡N, and O=O bonds) achieved via ePMR over the past 30 years were concisely discussed to highlight the unique advantages of ePMR. Promising research directions along with the advancement of ePMR for more challenging hydrogenation reactions are also proposed. Finally, we provide a prospect for future development of this distinctive hydrogenation strategy using hydrogen-permeable membrane electrodes.

Has collateral blood flow any effect on restenosis rate? Our experience.

Objectives: Restenosis is one of the important factors affecting the effectiveness of percutaneous transluminal angioplasty and stenting in the treatment of intracranial atherosclerotic stenosis. We aimed to clarify whether recruitable collateral flow could cause restenosis in patients treated with percutaneous transluminal angioplasty and stenting. Material and methods: Our study retrospectively analyzed patients with symptomatic severe intracranial atherosclerotic stenosis (≥70%) who underwent percutaneous transluminal angioplasty and stenting. We enrolled 28 patients with restenosis and 71 patients without restenosis. We analyzed baseline data, perioperative events, and follow-up results of patients in the two groups. Binary logistic regression analysis was used to identify restenosis predictors. Results: For preoperative stroke, the restenosis group had a greater likelihood of having a previous stroke (89.3%), which was less prevalent in the non-restenosis group (66.2%) (P = 0.020). The restenosis group had a higher rate of re-stroke (21.4 vs. 4.2%, P = 0.022). After binary logistic regression analysis, collateral circulation and residual stenosis were independent risk factors of restenosis, with overall risk (95% confidence intervals) of 5.034 (1.484-4.066, P < 0.001) and 1.064 (1.006-1.125, P = 0.030), respectively. Restenosis risk increased 1.456-fold for each collateral circulation grade increase. However, for each 1% increase in residual stenosis, restenosis risk increased by 5.9% (P = 0.03). The chance of restenosis is minimal when the residual stenosis rate after percutaneous transluminal angioplasty and stent implantation is 15.85%. Conclusions: Good collateral circulation was significantly associated with restenosis in patients undergoing intracranial angioplasty, the residual stenosis rate tends to be 15.85% to reduce restenosis risk. Compared to patients with restenosis, those without restenosis have a low stroke risk during follow-up.

Virtual screening of natural products targeting ubiquitin-specific protease 7.

Ubiquitin-specific protease 7 (USP7) is a promising prognostic and druggable target for cancer therapy. Inhibition of USP7 can activate the MDM2-P53 signaling pathway, thereby promoting cancer cell apoptosis. This study based on watvina molecular docking of virtual screening method and biological evaluation found the new USP7 inhibitors targeting catalytic active site. Three hits were screened from 3760 natural products and validated as USP7 inhibitors by enzymatic and kinetic assays. The IC50 values of scutellarein (Scu), semethylzeylastera (DML) and salvianolic acid C (SAC) were 3.017, 6.865 and 8.495 µM, respectively. Further, we reported that the hits could downregulate MDM2 and activate p53 signal pathway in HCT116 cells. Molecular dynamics simulation was used to investigate the binding mechanism of USP7 to Scu, the compound with the best performance, which formed stable contact with Val296, Gln297, Phe409, Tyr465 and Tyr514. These interactions are essential for maintaining the biological activity of Scu. Three natural products are suitable as lead compounds for the development of novel USP7 inhibitors, especially anti-colon cancer drugs.Communicated by Ramaswamy H. Sarma.

Design, Synthesis, and Biological Evaluation of Hydrophobic-Tagged Glutathione Peroxidase 4 (GPX4) Degraders.

Ferroptosis is an iron-dependent form of oxidative cell death induced by lipid peroxidation accumulation. Glutathione peroxidase 4 (GPX4) plays a key role in the regulation of ferroptosis and is considered to be a promising therapeutic target for cancer and other human diseases. Herein, we describe our design, synthesis, and biological evaluation of a series of HyT-based degraders of the GPX4. One of the most promising compounds, 7b (ZX782), effectively induces dose- and time-dependent degradation of GPX4 protein and potently suppresses the growth of human fibrosarcoma HT1080 cells, which are highly sensitive to ferroptosis and widely used for evaluating compound specificity in ferroptosis. Mechanism investigation indicated that 7b depletes GPX4 through both the ubiquitin-proteasome and the autophagy-lysosome. Furthermore, the degradation of GPX4 induced by 7b could significantly increase the accumulation of lipid reactive oxygen species (ROS) in HT1080 cells, ultimately leading to ferroptosis. Overall, compound 7b exhibits robust potency in depleting endogenous GPX4, thereby modulating ferroptosis in cancer cells.

TNFRSF19 within the 13q12.12 Risk Locus Functions as a Lung Cancer Suppressor by Binding Wnt3a to Inhibit Wnt/ß-Catenin Signaling.

Cancer risk loci provide special clues for uncovering pathogenesis of cancers. The TNFRSF19 gene located within the 13q12.12 lung cancer risk locus encodes TNF receptor superfamily member 19 (TNFRSF19) protein and has been proved to be a key target gene of a lung tissue-specific tumor suppressive enhancer, but its functional role in lung cancer pathogenesis remains to be elucidated. Here we showed that the TNFRSF19 gene could protect human bronchial epithelial Beas-2B cells from pulmonary carcinogen nicotine-derived nitrosamine ketone (NNK)-induced malignant transformation. Knockout of the TNFRSF19 significantly increased NNK-induced colony formation rate on soft agar. Moreover, TNFRSF19 expression was significantly reduced in lung cancer tissues and cell lines. Restoration of TNFRSF19 expression in A549 lung cancer cell line dramatically suppressed the tumor formation in xenograft mouse model. Interestingly, the TNFRSF19 protein that is an orphan membrane receptor could compete with LRP6 to bind Wnt3a, thereby inhibiting the Wnt/ß-catenin signaling pathway that is required for NNK-induced malignant transformation as indicated by protein pulldown, site mutation, and fluorescence energy resonance transfer experiments. Knockout of the TNFRSF19 enhanced LRP6-Wnt3a interaction, promoting ß-catenin nucleus translocation and the downstream target gene expression, and thus sensitized the cells to NNK carcinogen. In conclusion, our study demonstrated that the TNFRSF19 inhibited lung cancer carcinogenesis by competing with LRP6 to combine with Wnt3a to inhibit the Wnt/ß-catenin signaling pathway. IMPLICATIONS: These findings revealed a novel anti-lung cancer mechanism, highlighting the special significance of TNFRSF19 gene within the 13q12.12 risk locus in lung cancer pathogenesis.

Coordination Engineering of Heteronuclear Fe-Mo Dual-Atom Catalyst for Promoted Electrocatalytic Nitrogen Fixation: A DFT Study.

Developing efficient nanostructured electrocatalysts for N2 reduction to NH3 under mild conditions remains a major challenge. The Fe-Mo cofactor serves as the archetypal active site in nitrogenase. Inspired by nitrogenase, we designed a series of heteronuclear dual-atom catalysts (DACs) labeled as FeMoN6-a Xa (a=1, 2, 3; X=B, C, O, S) anchored on the pore of g-C3 N4 to probe the impact of coordination on FeMo-catalyzed nitrogen fixation. The stability, reaction paths, activity, and selectivity of 12 different FeMoN6-a Xa DACs have been systematically studied using density functional theory. Of these, four DACs (FeMoN5 B1 , FeMoN5 O1 , FeMoN4 O2 , and FeMoN3 C3 ) displayed promising nitrogen reduction reaction (NRR) performance. Notably, FeMoN5 O1 stands out with an ultralow limiting potential of -0.11 V and high selectivity. Analysis of the density of states and charge/spin changes shows FeMoN5 O1 's high activity arises from optimal N2 binding on Fe initially and synergy of the FeMo dimer enabling protonation in NRR. This work contributes to the advancement of rational design for efficient NRR catalysts by regulating atomic coordination environments.

Dormancy and double-activation strategy for construction of high-performance mixed-matrix membranes.

Mixed-matrix membranes (MMMs) have the potential for energy-efficient gas separation by matching the superior mass transfer and anti-plasticization properties of the fillers with processability and scaling up features of the polymers. However, construction of high-performance MMMs has been prohibited due to low filler-loading and the existence of interfacial defects. Here, high MOF-loaded, i.e., 55 wt %, MMMs are developed by a 'dormancy and double-activation' (DDA) strategy. High MOF precursor concentration suppresses crystallization in the membrane casting solution, realizing molecular level mixing of all components. Then, the polymeric matrix was formed with uniform encapsulation of MOF nutrients. Subsequently, double-activation was employed to induce MOF crystallization: the alkali promotes MOFs nucleation to harvest small porous nanocrystals while excessive ligands activate the metal ions to enhance the MOFs conversion. As such, quasi-semi-continuous mass transfer channels can be formed in the MMMs by the connected MOFs nanocrystals to boost the gas permeability. The optimized MMM shows significantly ameliorated CO2 permeability, i.e., 2841 Barrer, five-fold enhancement compared with pristine polymer membrane, with a good CO2 /N2 selectivity of 36. Besides, the nanosized MOFs intensify their interaction with polymer chains, endowing the MMMs with good anti-plasticization behaviour and stability, which advances practical application of MMMs in carbon capture.

Positive Predictive Value of Cirrhosis and Chronic Pancreatitis Diagnoses in Individuals with Alcohol Use Disorder: A Single-Center Study.

BACKGROUND: Although accuracy of diagnosis codes for cirrhosis and chronic pancreatitis (CP) has been evaluated in multiple studies, none have focused on patients with alcohol use disorders (AUD). We evaluated the positive predictive value (PPV) for a verified diagnosis of cirrhosis and CP in AUD patients treated at a tertiary care center. METHODS: We performed a detailed review of electronic health records for AUD patients assigned ICD-9 or 10 codes for alcoholic cirrhosis (ALC) (n = 199), CP (n = 200), or both (n = 200). We calculated PPV for a verified diagnosis of cirrhosis and CP and performed multivariable regression analysis to assess the impact of relevant factors on PPV for a verified diagnosis. RESULTS: PPV of cirrhosis was 81.2% (95% CI 77.0 to 84.9%) which increased to 87.5% (95% CI 83.8 to 90.6%) if the definition was relaxed to include alcohol-related hepatitis. PPV of CP was 54.5% (95% CI 49.5 to 59.5%) which increased to 78% (95% CI 73.6 to 82.0%) when recurrent acute pancreatitis was included in the definition. In multivariable analyses, the odds of a verified diagnosis were significantly higher in individuals aged 65+ years for both cirrhosis (OR 12.23, 95% CI 2.19 to 68.42) and CP (OR 8.84, 95% CI 2.7 to 28.93) and in ever smokers for CP (OR 1.95, 95% CI 1.05 to 3.65). CONCLUSION: PPV for diagnosis codes in AUD patients is high for a verified diagnosis of cirrhosis but only modest for CP. While administrative datasets can provide reliable information for cirrhosis, future studies should focus on ways to boost the diagnostic validity of administrative datasets for CP.