Kallikrein inhibitor derived from immunoglobulin heavy chain junction region possesses anti-thromboinflammation potential.

Influenza vaccination is associated with a reduced incidence of cardiovascular events, cardiovascular death, and all-cause mortality. However, the functional role of the associated immunoglobulin remains unclear. This study identified a specific influenza-related immunoglobulin heavy chain junction region sequence (Ser-Leu-Gly-Ala-Ser-Asp, SD6) that inhibited plasma kallikrein (PKa) activity to resist thromboinflammatory responses and stroke injury. PKa is considered an attractive therapeutic target for alleviating the complications of thrombophilia-induced inflammation. In vitro, SD6 prolonged plasma recalcification and activated partial thromboplastin time, with no effects on bleeding risk-related prothrombin time, indicating selective inhibition of the intrinsic coagulation pathway. Correspondingly, at doses ranging from 0.25 to 4 mg/kg, SD6 attenuated arterial and cortical venous thrombosis in FeCl3-induced and photochemically induced mice, without impacting hemorrhage risk, and further mitigated cerebral inflammatory injury in a mouse model of transient middle cerebral artery occlusion ischemic stroke. These findings suggest that SD6 may serve as a potential therapeutic agent for the treatment of thromboinflammatory conditions.

Construction and characterization of Aeromonas hydrophila crp and fur deletion mutants and evaluation of its potential as live-attenuated vaccines in crucian carp.

Aeromonas hydrophila (A. hydrophila) is a typical zoonotic pathogenic bacterium that infects humans, animals, and fish. It has been reported that the Fur, a Fe2+ regulatory protein, and the Crp, a cAMP receptor protein, play important roles in bacterial virulence in many bacteria, but no research has been investigated on A. hydrophila. In this study, the Δfur and Δcrp mutant strains were constructed by the suicide plasmid method. These two mutant strains exhibited a slightly diminished bacterial growth and also were observed some alterations in the number of outer membrane proteins, and the disappearance of hemolysis in the Δcrp strain. Animal experiments of crucian carp showed that the Δfur and Δcrp mutant strains significantly decreased virulence compared to the wild-type strain, and both mutant strains were able to induce good immune responses by two kinds of administration routes of intraperitoneal immunization (i.p) and immersion immunization, and the protection rates through intraperitoneal injection of Δfur and Δcrp to crucian carp were as high as 83.3 % and 73.3 %, respectively, and immersion immunization route of Δfur and Δcrp to crucian carp provided protection as high as 40 % and 20 %, respectively. These two mutant strains showed abilities to induce changes in enzymatic activities of the non-specific enzymes SOD, LZM, AKP, and ACP in crucian carp. Together, these results indicated the Δfur and Δcrp mutants were safe and effective candidate vaccine strains, showing good protection against the wild-type A. hydrophila challenge.

Chiral MoS2@BC fibrous membranes selectively promote peripheral nerve regeneration.

BACKGROUND: Molybdenum disulfide (MoS2) has excellent physical and chemical properties. Further, chiral MoS2 (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear. METHODS: In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months. RESULTS: These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group. CONCLUSION: We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.

Prevalence and risk factors associated with dehydration of patients with dysphagia in eastern China: A cross-sectional study.

AIMS: Dehydration is one of the common complications of dysphagia and poses significant risks including hospitalization and mortality, but the relationship between dysphagia and dehydration has received little attention. This study aims to determine the prevalence and risk factors for dehydration of patients with dysphagia in eastern China, and to provide reference for early identification and prevention of dehydration. METHODS: A descriptive, cross-sectional design was conducted. Three hundred and thirty-seven (n = 337) patients with dysphagia participated in the study between August and December 2022. Information relating to participants' demographic variables, nutrition, cognition, functional, hydration status and fluid intake was collected. Univariate analysis was used to examine related impact factors, and then binary logistic regression analysis was conducted to determine reliable impact factors. RESULTS: Among 337 patients with dysphagia, the average age was 63.47 ± 16.96, most participants were male (72.1%) and married (91.7%). The prevalence of dehydration was calculated to be 43.9%, the mean plasma osmolality score was 293.53 mmol/L. Diseases with the highest prevalence were stroke (78.3%), followed by hypertension (63.5%). The risk for dehydration increased with older age, usage of more medicines such as diuretics and beta-blockers, worse functional status and lower fluid intake. CONCLUSION: This study found a high percentage of dehydration in patients with dysphagia. Findings can provide a basis for targeted nursing interventions for clinical prevention and treatment of dehydration.

Nanoconstruction on Living Cell Surfaces with Cucurbit[7]uril-Based Supramolecular Polymer Chemistry: Toward Cell-Based Delivery of Bio-Orthogonal Catalytic Systems.

Employing living cells as carriers to transport transition metal-based catalysts for target-specific bio-orthogonal catalysis represents a cutting-edge approach in advancing precision biomedical applications. One of the initial hurdles in this endeavor involves effectively attaching the catalysts to the carrier cells while preserving the cells' innate ability to interact with biological systems and maintaining the unaltered catalytic activity. In this study, we have developed an innovative layer-by-layer method that leverages a noncovalent interaction between cucurbit[7]uril and adamantane as the primary driving force for crafting polymeric nanostructures on the surfaces of these carrier cells. The strong binding affinity between the host-guest pair ensures the creation of a durable polymer coating on the cell surfaces. Meanwhile, the layer-by-layer process offers high adaptability, facilitating the efficient loading of bio-orthogonal catalysts onto cell surfaces. Importantly, the polymeric coating shows no discernible impact on the cells' physiological characteristics, including their tropism, migration, and differentiation, while preserving the effectiveness of the bio-orthogonal catalysts.

Optical-fiber-integrated high-speed organic phototransistor with broadband imaging capacity.

Fiber optic communication is becoming the central pillar of modern high-speed communication technology, which involves the abundant fiber components. Currently, most of photodetectors are fabricated on the silicon chip, so mass fiber-to-chip interfaces increase the complexity of advanced optoelectronic system, and also grow the risk of optical information loss. Here, we report an all-fiber organic phototransistor by employing rubrene single crystal and few-layer graphene to realize the "plug-to-play" operation. The device shows a broadband photoresponse from the ultraviolet to visible range, with fast response times of approximately 130/170 µs and reasonable specific detectivity of 6 × 109 Jones, which is close to the level of commercial on-chip device. Finally, several imaging applications are successfully demonstrated by deploying this all-fiber device. Our work provided an efficient strategy for fabricating all-fiber organic devices, and confirmed their significant potential in future optical fiber optoelectronics.

Copy number variant analysis for syndromic congenital heart disease in the Chinese population.

BACKGROUND: Syndromic congenital heart disease (CHD) is among the most severe conditions in the pediatric population. Copy number variant (CNV) is an important cause of syndromic CHD, but few studies focused on CNVs related to these patients in China. The present study aimed to identify pathogenic CNVs associated with syndromic CHD in the Chinese population. METHODS: A total of 109 sporadic patients with syndromic CHD were applied chromosomal microarray analysis (CMA). Phenotype spectrum of pathogenic or likely pathogenic CNVs was analyzed. CHD-related genes were prioritized from genes within pathogenic or likely pathogenic CNVs by VarElect, OVA, AMELIE, and ToppGene. RESULTS: Using CMA, we identified 43 candidate CNVs in 37/109 patients. After filtering CNVs present in the general population, 29 pathogenic/likely pathogenic CNVs in 24 patients were identified. The diagnostic yield of CMA for pathogenic/likely pathogenic CNVs was 23.1% (24/104), excluding 5 cases with aneuploidies or gross chromosomal aberrations. The overlapping analysis of CHD-related gene lists from different prioritization tools highlighted 16 CHD candidate genes. CONCLUSION: As the first study focused on CNVs in syndromic CHD from the Chinese population, this study reveals the importance of CMA in exploring the genetic etiology of syndromic CHD and expands our understanding of these complex diseases. The bioinformatic analysis of candidate genes suggests several CHD-related genes for further functional research.

Antibacterial peptide PMAP-37(F34-R), expressed in Pichia pastoris, is effective against pathogenic bacteria and preserves plums.

BACKGROUND: Recently, researchers have focused on the search for alternatives to conventional antibiotics. Antimicrobial peptides are small bioactive peptides that regulate immune activation and have antibacterial activity with a reduced risk of bacterial resistance. Porcine myeloid antibacterial peptide 37 (PMAP-37) is a small-molecule peptide with broad-spectrum antibacterial activity isolated from pig bone marrow, and PMAP-37(F34-R) is its analogue. In this study, PMAP-37(F34-R) was recombinantly expressed in Pichia pastoris, and the recombinant peptide was further investigated for its antibacterial properties, mechanism and preservative in plums. RESULTS: To obtain a Pichia pastoris strain expressing PMAP-37(F34-R), we constructed a plasmid expressing recombinant PMAP-37(F34-R) (pPICZα-PMAP-37(F34-R)-A) and introduced it into Pichia pastoris. Finally, we obtained a highly active recombinant peptide, PMAP-37(F34-R), which inhibited the activity of both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration is 0.12-0.24 µg/mL, and it can destroy the integrity of the cell membrane, leading to cell lysis. It has good stability and is not easily affected by the external environment. Hemolysis experiments showed that 0.06 µg/mL-0.36 µg/mL PMAP-37(F34-R) had lower hemolysis ability to mammalian cells, and the hemolysis rate was below 1.5%. Additionally, 0.36 µg/mL PMAP-37(F34-R) showed a good preservative effect in plums. The decay and weight loss rates of the treated samples were significantly lower than those of the control group, and the respiratory intensity of the fruit was delayed in the experimental group. CONCLUSIONS: In this study, we constructed a recombinant Pichia pastoris strain, which is a promising candidate for extending the shelf life of fruits and has potential applications in the development of new preservatives.

Periconception Red Blood Cell Folate and Offspring Congenital Heart Disease : Nested Case-Control and Mendelian Randomization Studies.

BACKGROUND: Periconception folic acid supplementation has been suggested to protect against congenital heart disease (CHD), but the association between maternal red blood cell (RBC) folate, the gold-standard biomarker of folate exposure, and subsequent offspring CHD risk is lacking. OBJECTIVE: To quantify the association between periconception maternal RBC folate and offspring CHD risk. DESIGN: Prospective, nested, case-control study and 1-sample Mendelian randomization. (ClinicalTrials.gov: NCT02737644). SETTING: 29 maternity institutions in 12 districts of Greater Shanghai, China. PARTICIPANTS: All 197 mothers of offspring with CHD and 788 individually matched mothers of unaffected offspring from the SPCC (Shanghai Preconception Cohort). MEASUREMENTS: Maternal RBC folate was measured before or at early pregnancy. Odds ratios [ORs] were estimated using conditional logistic regression after adjustment for covariates. Mendelian randomization was done using the methylenetetrahydrofolate reductase (MTHFR) C677T as the genetic instrument. RESULTS: Case patients had lower median maternal RBC folate concentrations than control participants (714 nmol/L [interquartile range, 482 to 1008 nmol/L] vs. 788 nmol/L [557 to 1094 nmol/L]). Maternal RBC folate concentrations were inversely associated with offspring CHD (adjusted OR per 100 nmol/L, 0.93 [95% CI, 0.89 to 0.99]). The adjusted OR for mothers with periconception RBC folate of 906 nmol/L or more (vs. <906 nmol/L) was 0.61 (CI, 0.40 to 0.93). Mendelian randomization showed that each 100-nmol increase in maternal RBC folate concentrations was significantly associated with reduced offspring CHD risk (OR, 0.75 [CI, 0.61 to 0.92]). LIMITATION: Potential confounding due to unmeasured covariates in the nested case-control study. CONCLUSION: Higher maternal RBC folate is associated with reduced offspring CHD risk. For primary CHD prevention, higher target RBC folate levels than currently recommended for neural tube defect prevention may be needed and warrant further study. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.

Genome-Wide Identification, Characterization, and Expression Analysis of SPIRAL1 Family Genes in Legume Species.

The SPIRAL1 (SPR1) gene family encodes microtubule-associated proteins that are essential for the anisotropic growth of plant cells and abiotic stress resistance. Currently, little is known about the characteristics and roles of the gene family outside of Arabidopsis thaliana. This study intended to investigate the SPR1 gene family in legumes. In contrast to that of A. thaliana, the gene family has undergone shrinking in the model legume species Medicago truncatula and Glycine max. While the orthologues of SPR1 were lost, very few SPR1-Like (SP1L) genes were identified given the genome size of the two species. Specifically, the M. truncatula and G. max genomes only harbor two MtSP1L and eight GmSP1L genes, respectively. Multiple sequence alignment showed that all these members contain conserved N- and C-terminal regions. Phylogenetic analysis clustered the legume SP1L proteins into three clades. The SP1L genes showed similar exon-intron organizations and similar architectures in their conserved motifs. Many essential cis-elements are present in the promoter regions of the MtSP1L and GmSP1L genes associated with growth and development, plant hormones, light, and stress. The expression analysis revealed that clade 1 and clade 2 SP1L genes have relatively high expression in all tested tissues in Medicago and soybean, suggesting their function in plant growth and development. MtSP1L-2, as well as clade 1 and clade 2 GmSP1L genes, display a light-dependent expression pattern. The SP1L genes in clade 2 (MtSP1L-2, GmSP1L-3, and GmSP1L-4) were significantly induced by sodium chloride treatment, suggesting a potential role in the salt-stress response. Our research provides essential information for the functional studies of SP1L genes in legume species in the future.

Assessing runoff control of low impact development in Hong Kong's dense community with reliable SWMM setup and calibration.

Low impact development (LID) is a sustainable practice to managing urban runoff. However, its effectiveness in densely populated areas with intense rainfall, such as Hong Kong, remains unclear due to limited studies with similar climate conditions and urban patterns. The highly mixed land use and complicated drainage network present challenges for preparing a Storm Water Management Model (SWMM). This study proposed a reliable framework for setting up and calibrating SWMM by integrating multiple automated tools to address these issues. With a validated SWMM, we examined LID's effects on runoff control in a densely built catchment of Hong Kong. A designed full-scale LID implementation can reduce total and peak runoffs by around 35-45% for 2, 10 and 50-year return rainfalls. However, LID alone may not be adequate to handle the runoff in densely built areas of Hong Kong. As the rainfall return period increases, total runoff reduction increases, but peak runoff reduction remains close. Percentages of reduction in total and peak runoffs decline. The marginal control diminishes for total runoff while remaining constant for peak runoff when increasing the extent of LID implementation. In addition, the study identifies the crucial design parameters of LID facilities using global sensitivity analysis. Overall, our study contributes to accelerating the reliable application of SWMM and deepening the understanding of the effectiveness of LID in ensuring water security in densely built urban communities located near the humid-tropical climate zone, such as Hong Kong.

The Expression of Antibacterial Peptide Turgencin A in Pichia pastoris and an Analysis of Its Antibacterial Activity.

Antibiotic resistance to pathogenic bacteria is becoming an increasing public health threat, and identifying alternatives to antibiotics would be an effective solution to the problem of drug resistance. Antimicrobial peptides are small peptides produced by various organisms; they are considered to be adequate antibiotic substitutes because they have intense, broad-spectrum antibacterial activity and stability, are widely available, and target strains do not quickly develop resistance. Recent research on antimicrobial peptides has shown that they have broad potential for applications in medicine, agriculture, food, and animal feed. Turgencin A is a potent antimicrobial peptide isolated from the Arctic sea squirt. We established a His-tagged expression system for Pichia pastoris and developed a rTurgencin A using the recombinant expression in Pichia pastoris with nickel column purification. This antimicrobial peptide showed intense antimicrobial activity against Gram-positive and Gram-negative bacteria and a good stability at most temperatures and pHs, as well as in various protease and salt ion concentrations, but underwent a significant decrease in stability in high-temperature and low-pH environments. Turgencin A induced bacterial membrane rupture, resulting in content leakage and subsequent cell death. It was also shown to have low hemolytic activity. This study provides primary data for the industrial production and application of the antimicrobial peptide Turgencin A.

RAA Enzyme Is a New Family of Class A Extended-Spectrum ß-Lactamase from Riemerella anatipestifer Strain RCAD0122.

Whole-genome sequencing of Riemerella anatipestifer isolate RCAD0122 revealed a chromosomally located ß-lactamase gene, blaRAA-1, which encoded a novel class A extended-spectrum ß-lactamase (ESBL), RAA-1. RAA-1 shared ≤65% amino acid sequence identity with other characterized ß-lactamases. The kinetic assay of native purified RAA-1 revealed ESBL-like hydrolysis activity. Furthermore, blaRAA-1 could be transferred to a homologous strain by natural transformation. However, an epidemiological study showed that the blaRAA-1 gene is not prevalent currently.

Grazing exclusion had greater effects than nitrogen addition on soil and plant community in a desert steppe, Northwest of China.

BACKGROUND: The impacts of increasing nitrogen (N) deposition and overgrazing on terrestrial ecosystems have been continuously hot issues. Grazing exclusion, aimed at restoration of grassland ecosystem function and service, has been extensively applied, and considered a rapid and effective vegetation restoration method. However, the synthetic effects of exclosure and N deposition on plant and community characteristics have rarely been studied. Here, a 4-year field experiment of N addition and exclusion treatment had been conducted in the desert steppe dominated by Alhagi sparsifolia and Lycium ruthenicum in northwest of China, and the responses of soil characteristics, plant nutrition and plant community to the treatments had been analyzed. RESULTS: The grazing exclusion significantly increased total N concentration in the surface soil (0-20 cm), and increased plant height, coverage (P < 0.05) and aboveground biomass. Specifically, A. sparsifolia recovered faster both in individual and community levels than L. ruthenicum did after exclusion. There was no difference in response to N addition gradients between the two plants. CONCLUSIONS: Our findings suggest that it is exclusion rather than N addition that has greater impacts on soil properties and plant community in desert steppe. Present N deposition level has no effect on plant community of desert steppe based on short-term experimental treatments.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Ascorbic acid functionalized anti-aggregated Au nanoparticles for ultrafast MEF and SERS detection of tartrazine: an ultra-wide piecewise linear range study.

Tartrazine, as a synthetic food colorant, is harmful to health upon excessive intake. In this study, we developed a simple, sensitive and ultrafast method to detect tartrazine effectively. Specifically, we successfully used ascorbic acid-functionalized anti-aggregated Au nanoparticles (AuNPs) as enhanced substrates to detect tartrazine in drinks using metal enhanced fluorescence (MEF) and surface-enhanced Raman scattering (SERS) piecewise linearly. The fluorescence intensity and Raman signals of the tartrazine solution enhanced after the addition of AuNPs. There was a good linear correlation between the fluorescence intensity and the concentration of tartrazine from 2.0 µM to 40.0 µM, and the limit of detection (LoD) was 15.4 nM. In addition, the Raman intensity also increased linearly with an increase in the concentration of tartrazine in a wide range (1.0 × 10-5 µM to 1.0 × 10-1 µM) and a lower LoD (0.8 pM) was achieved compared with the results from the fluorescence technique. Both fluorescence and SERS can immediately detect tartrazine in drinks after the substrate was mixed with analytes. Hence, the as-prepared anti-aggregated AuNPs as substrate material achieved a highly sensitive, selective and ultrafast detection of tartrazine via fluorescence and Raman techniques in a wide detection range, providing a novel strategy for the detection of food additives.

Maternal liver dysfunction in early pregnancy predisposes to gestational diabetes mellitus independent of preconception overweight: A prospective cohort study.

OBJECTIVE: To evaluate whether the associations of maternal liver dysfunction and liver function biomarkers (LFBs) with gestational diabetes mellitus (GDM) are independent of overweight. DESIGN: Prospective cohort study. METHODS: A sub-cohort of pregnant women with seven LFBs examined at 9-13 weeks of gestation and with complete GDM evaluation at mid-gestation were extracted from the prospective Shanghai Preconception Cohort Study. Associations of liver dysfunction, defined as having any elevated LFB levels, and individual LFB levels with GDM incidence were assessed by adjusting body mass index and other covariates in the multivariable logistic regression model. Odds ratios (ORs) and 95% CI were reported. MAIN OUTCOME MEASURES: Incident GDM. RESULTS: Among 6211 pregnant women, 975 (15.7%) developed GDM. Liver dysfunction was associated with increased odds of GDM (OR 1.63; 95% CI 1.38-1.92). This association persisted after adjustment for BMI (adjusted OR [aOR] 1.37; 95% CI 1.15-1.63). Higher γ-glutamyl transferase, alanine aminotransferase, alkaline phosphatase, and albumin levels were also linked with GDM (aOR per 1 SD: 1.15, 95% CI 1.08-1.23; 1.10, 1.03-1.17; 1.21, 1.13-1.29 and 1.19, 1.11-1.27, respectively). Similar magnitudes of associations were observed between normal weight and overweight pregnant women. CONCLUSION: Maternal liver dysfunction in early pregnancy predisposes women to subsequent GDM, and this association is independent of being overweight preconception. Our findings of an increased risk even in normal-weight pregnant women adds new mechanistic insights about the pathophysiological role of liver function in GDM aetiology. TWEETABLE ABSTRACT: Maternal liver dysfunction in early pregnancy is associated with GDM incidence independent of preconception overweight.

Novel Nitric Oxide Donor Dinitroazetidine-Coumarin Hybrids as Potent Anti-Intrahepatic Cholangiocarcinoma Agents.

Intrahepatic cholangiocarcinoma (iCC) is a serious liver cancer threatening human health. However, there are a few chemotherapeutic drugs for the treatment of iCC in the clinic. It is extremely urgent to develop new drugs for iCC. In this study, twenty dinitroazetidine and coumarin hybrids were synthesized and evaluated anti-iCC bioactivity as a new type of nitric oxide (NO) donors. Among them, compounds 2-5 and 21 showed a higher antiproliferative activity against RBE cell lines (human intrahepatic cholangiocarcinoma cell lines) and low cytotoxicity in nontumor cells (HOSEpiC and T29). The preliminary study of pharmacology mechanism indicated that compounds 2-5 and 21 could release effective concentration of NO in RBE cell lines, which leaded to inhibit the proliferation of RBE cell lines. The research results revealed that compound 3 inhibited the proliferation of RBE cell lines by inducing apoptosis and arresting cell cycle at G2/M phase. Additionally, compound 3 had acceptable metabolic stability. Therefore, compound 3 was merited to further explore for developing a desirable NO donor lead with anti-iCC activity.

Sphagnum Inspired g-C3 N4 Nano/Microspheres with Smaller Bandgap in Heterojunction Membranes for Sunlight-Driven Water Purification.

Membrane separation is recognized as one of the most effective strategies to treat the complicated wastewater system for economic development. However, serious membrane fouling has restricted its further application. Inspired by sphagnum, a 0D/2D heterojunction composite membrane is engineered by depositing graphitic carbon nitride nano/microspheres (CNMS) with plentiful wrinkles onto the polyacrylic acid functionalized carbon nanotubes (CNTs-PAA) membrane through hydrogen bond force. Through coupling unique structure and chemistry properties, the CNTs-PAA/CNMS heterojunction membrane presents superhydrophilicity and underwater superoleophobicity. Furthermore, thanks to the J-type aggregates during the solvothermal process, it is provided with a smaller bandgap (1.77 eV) than the traditional graphitic carbon nitride (g-C3 N4 ) sheets-based membranes (2.4-2.8 eV). This feature endows the CNTs-PAA/CNMS membrane with superior visible-light-driven self-cleaning ability, which can maintain its excellent emulsion separation (with a maximum flux of 5557 ± 331 L m-2 h-1 bar-1 and an efficiency of 98.5 ± 0.6%), photocatalytic degradation (with an efficiency of 99.7 ± 0.2%), and antibacterial (with an efficiency of ≈100%) ability even after cyclic experimental processes. The excellent self-cleaning performance of this all-in-one membrane represents its potential value for water purification.

Ultralow Icing Adhesion of a Superhydrophobic Coating Based on the Synergistic Effect of Soft and Stiff Particles.

A novel superhydrophobic coating composed of soft polydimethylsiloxane microspheres and stiff SiO2 nanoparticles was developed and prepared. This superhydrophobic coating showed excellent superhydrophobicity with a large water contact angle of 171.3° and also exhibited good anti-icing performance and ultralow icing adhesion of 1.53 kPa. Furthermore, the superhydrophobic coating displayed good icing/deicing cycle stability, in which the icing adhesion was still less than 10.0 kPa after 25 cycles. This excellent comprehensive performance is attributed to stress-localization between ice and the surface, resulting from the synergistic effect of soft and stiff particles. This work thus opens a new avenue to simultaneously optimize the anti-icing and icephobic performance of a superhydrophobic surface for various applications.