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The present study examined the pharmacokinetics of IMM‐H012 in rat plasma, utilizing ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS). Internal standard cilostazol was employed, and plasma samples were processed using acetonitrile precipitation. A mobile phase (acetonitrile–0.1% formic acid in water) with gradient elution was used to achieve chromatographic separation using a UPLC BEH C18 column. In multiple reaction monitoring mode, electrospray ionization MS/MS was utilized in positive ionization mode. Based on findings, the lower limit of quantification was 2 ng/mL, and the linearity of IMM‐H012 in rat plasma was found to be acceptable within the range of 2–2000 ng/mL (R2 > 0.995). The intra‐day and inter‐day precision relative standard deviation was less than 14% of IMM‐H012 in rat plasma. The matrix effect was within the range of 102%–107%, and the accuracy ranged from 92% to 113%. Pharmacokinetics of IMM‐H012 in rats after oral administration were successfully studied using UPLC‐MS/MS. [ABSTRACT FROM AUTHOR]

Metamaterials hold significant promise for enhancing the imaging capabilities of magnetic resonance imaging (MRI) machines as an additive technology, due to their unique ability to enhance local magnetic fields. However, despite their potential, the metamaterials reported in the context of MRI applications have often been impractical. This impracticality arises from their predominantly flat configurations and their susceptibility to shifts in resonance frequencies, preventing them from realizing their optimal performance. Here, a computational method for designing wearable and tunable metamaterials via freeform auxetics is introduced. The proposed computational‐design tools yield an approach to solving the complex circle packing problems in an interactive and efficient manner, thus facilitating the development of deployable metamaterials configured in freeform shapes. With such tools, the developed metamaterials may readily conform to a patient's knee, ankle, head, or any part of the body in need of imaging, and while ensuring an optimal resonance frequency, thereby paving the way for the widespread adoption of metamaterials in clinical MRI applications. [ABSTRACT FROM AUTHOR]

Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28‐day multi‐endpoint (Pig‐a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF‐treated groups (0.5, 5, and 50 μg/kg·bw/d), BPA group (10 μg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N‐ethyl‐N‐nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high‐dose recovery group (BPAF‐HR), oil recovery group (oil‐R), ENU recovery group (ENU‐R), and PBS recovery group (PBS‐R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood‐testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA. In this study, we used the in vivo genotoxicity integrative evaluation system to evaluate the genotoxicity under subacute exposure to BPAF and explore and compare the mechanism of BPAF and BPA in inducing DNA damage and testicular damage. Under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA. [ABSTRACT FROM AUTHOR]

Background: Executive function enhancement is considered necessary for improving the quality of life of patients with neurological or psychiatric disorders, such as attention‐deficit/hyperactivity disorder, obsessive‐compulsive disorder and Alzheimer's disease. Transcranial electrical stimulation (tES) has been shown to have some beneficial effects on executive functioning, but the quantification of these improvements remains controversial. We aimed to explore the potential beneficial effects on executive functioning induced by the use of transcranial alternating current stimulation (tACS)/transcranial direct current stimulation (tDCS) on the right inferior frontal gyrus (IFG) and the accompanying brain function variations in the resting state. Methods: We recruited 229 healthy adults to participate in Experiments 1 (105 participants) and 2 (124 participants). The participants in each experiment were randomly divided into tACS, tDCS, and sham groups. The participants completed cognitive tasks to assess behavior related to three core components of executive functions. Functional near‐infrared spectroscopy (fNIRS) was used to monitor the hemodynamic changes in crucial cortical regions in the resting state. Results: Inhibition and cognitive flexibility (excluding working memory) were significantly increased after tACS/tDCS, but there were no significant behavioral differences between the tACS and tDCS groups. fNIRS revealed that tDCS induced decreases in the functional connectivity (increased neural efficiency) of the relevant cortices. Conclusions: Enhancement of executive function was observed after tES, and the beneficial effects of tACS/tDCS may need to be precisely evaluated via brain imaging indicators at rest. tDCS revealed better neural benefits than tACS during the stimulation phase. These findings might provide new insights for selecting intervention methods in future studies and for evaluating the clinical efficacy of tES. [ABSTRACT FROM AUTHOR]

To explore the role of PDE4D in diabetic nephropathy (DN) and investigate whether resveratrol protects against DN via inhibiting PDE4D. Diabetic db/db mouse and glomerular mesangial cell line (GMCs) were used to investigate the role of PDE4D and the protective effect of resveratrol on renal fibrosis under high glucose (HG) environment. Resveratrol alleviated the progress of DN via inhibiting mitochondrial fragmentation and restoring the expression of PDE4D, PKA, phosphorylated Drp1‐Ser637 and Drp1 in kidney of db/db mice. In HG‐exposed GMCs, resveratrol treatment decreased the expression of PDE4D, increased PKA level, and inhibited Drp1‐mediated mitochondrial fission. In contrast, PDE4D over‐expression blunted the inhibitory effects of resveratrol on Drp1 expression and mitochondrial fission. Moreover, PKA inhibitor H89 blunted the effects of resveratrol on phosphorylated Drp1‐Ser637 expression and mitochondrial fission in HG‐treated GMCs. Inhibition of mitochondrial fission with Drp1 inhibitor Mdivi‐1 alleviated mitochondrial dysfunction in GMCs under HG. These findings indicate PDE4D plays an important role in the process of DN. Resveratrol attenuates the development of DN by preventing mitochondrial fission through inhibiting PDE4D, which regulates the expression of phosphorylated Drp1‐Ser637 directly. [ABSTRACT FROM AUTHOR]

Signal‐to‐noise ratio (SNR) is one of the most common metrics in assessing the image quality of magnetic resonance imaging (MRI). Among a host of technological developments, various wireless devices, including metamaterials and volumetric wireless resonators have been reported to enhance SNR by redistributing the radio frequency magnetic field in the near field region. While theoretically feasible, their widespread clinical adoption has been limited by their field inhomogeneity, limited spatial coverage and challenges in their applications to higher field (≥3.0T) MRI systems. In this study, a Helmholtz coil‐inspired volumetric wireless resonator (HVWR) featuring a uniform magnetic field enhancement within the resonator volume is reported. The HVWR is free from cables, adapters and interface boxes, allowing for ease of fabrication and straightforward installation. The resonator allows for resonance frequency tunability and adaptivity, enabling for passive detuning during the MRI transmission phase. Experimental validation using a 3.0T MRI system demonstrate a substantial SNR boost (5× or higher) being achieved in a region covering the average size of the human knee. This study offers an efficient and practical wireless solution for improved MRI image quality that may be applicable across a range of imaging applications. [ABSTRACT FROM AUTHOR]

Thiopurine dose optimization by thiopurine‐S‐methyltransferase (TPMT) or nudix hydrolase‐15 (NUDT15) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 months). Although laboratory monitoring of 6‐thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA‐thioguanine nucleotides (DNA‐TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA‐TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells < 3.5 × 109/L) were observed in 43 patients (14.0%), who had significantly higher DNA‐TG concentration than those without leucopenia (P = 4.1 × 10–9, 423.3 (~ 342.2 to 565.7) vs. 270.5 (~ 188.1 to 394.3) fmol/μg DNA). No difference in 6TGN concentrations between leucopenia and non‐leucopenia was found. With a DNA‐TG threshold of 340.1 fmol/μg DNA, 83.7% of leucopenia cases could be identified. Multivariate analysis showed that DNA‐TG was an independent risk factor for late leucopenia. Quantification of DNA‐TG, rather than 6TGN, can be applied to gauge thiopurine therapy after NUDT15 screening in Chinese patients with IBD. [ABSTRACT FROM AUTHOR]

Adrenomedullin (ADM) has beneficial effects on Leydig cells under pathological conditions, including lipopolysaccharide (LPS)‐induced orchitis. Our previous studies demonstrated that ADM exerts a restorative effect on steroidogenesis in LPS‐treated primary rat Leydig cells by attenuating oxidative stress, inflammation and apoptosis. In this study, we aim to investigate whether ADM inhibits Leydig cell dysfunction by rescuing steroidogenic enzymes in vivo. Rats were administered with LPS and injected with Ad‐ADM, an adeno‐associated virus vector that expressed ADM. Then, rat testes were collected for 3β‐hydroxysteroid dehydrogenase (3β‐HSD) immunofluorescence staining. Steroidogenic enzymes or steroidogenic regulatory factors or protein, including steroidogenic factor‐1 (SF‐1), liver receptor homologue‐1 (LRH1), Nur77, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), 3β‐HSD, cytochrome P450 17α‐hydroxylase/17, 20 lyase (CYP17) and 17β‐hydroxysteroid dehydrogenase (17β‐HSD), were detected via gene expression profiling and western blot analysis. Plasma testosterone concentrations were measured. Results showed that ADM may inhibit Leydig cell dysfunction by rescuing steroidogenic enzymes and steroidogenic regulatory factors in vivo. The reduction in the number of Leydig cells after LPS exposure was reversed by ADM. ADM rescued the gene or protein levels of SF‐1, LRH1, Nur77, StAR, P450scc, 3β‐HSD, CYP17 and 17β‐HSD and plasma testosterone concentrations. To summarize ADM could rescue some important steroidogenic enzymes, steroidogenic regulatory factors and testosterone production in Leydig cells in vivo. [ABSTRACT FROM AUTHOR]

The mycotoxin altertoxin I (ATX‐I) is one of secondary metabolites produced by Alternaria fungi and is frequently detected as food and feed contaminants. Little is known about the genotoxicity of the ATX‐I. In order to evaluate potential genotoxicity and general toxicity of ATX‐I, the novel 28‐day multiendpoint (Pig‐a assay + micronucleus [MN] test + comet assay) genotoxicity platform was applied. Male Sprague–Dawley (SD) rats were randomized to five groups (six rats per group), that is, a positive control group (N‐ethyl‐N‐nitrosourea [ENU], 40 mg/kg.bw/d), two solvent control groups (PBS and corn oil), and two ATX‐I‐treated groups (low‐dose group [1.10 μg/kg.bw/d] and high‐dose group [5.51 μg/kg.bw/d]). Treatments were administered by oral gavage to male SD rats for 28 consecutive days. Histopathological damages in the liver, kidney, and spleen were observed, but without significant changes in hematological and serum biochemical parameters. Genotoxic endpoints indicated that ATX‐I could cause DNA damage. To summarize, in a relatively low‐dose range, ATX‐I may not have direct genotoxicity in vivo but could induce liver, kidney, and spleen damage. General toxicity and genotoxicity of ATX‐I was evaluated with the multiendpoint assay in rats, combining the flow‐cytometric MN test, the comet assay, and the Pig‐a assay, and this is the first report of the in vivo genotoxicity of ATX‐I. The results indicated that constant exposure to ATX‐I could cause DNA damage and induce liver, kidney, and spleen damage. [ABSTRACT FROM AUTHOR]

We sought to evaluate the association between sexual dysfunction and chronic retention of foreign bodies in the lower urinary tract (LUT) for long‐term periods (≧4 weeks) in patients seen at three medical centres between January 2015 and September 2020, followed by assessing the impact of long‐term retention of a foreign body in the LUT on sexual function. Thirty‐eight patients were studied in the long‐term group, among whom the aetiology of the foreign bodies included sexual desire with masturbation (n = 22, 58%), sexual inquisitiveness (n = 10, 26%), dysuria (n = 3, 8%) and seeking to relieve itching (n = 3, 8%). There were various types of foreign bodies, including a string of magnetic beads (n = 13), a thermometer (n = 5), plastic electric wire (n = 5) and others (n = 15). All cases presented with sexual dysfunction and LUT symptoms. Three months after foreign body removal, sexual dysfunction symptoms were significantly improved in 22 male cases and seven female cases. We found that chronic retention of foreign bodies in the LUT causes sexual dysfunction in both men and women. The psychological effects of fear may prevent these patients from seeking medical help. Thus, education on sexual medicine and timely removal of foreign bodies is necessary to avert sexual dysfunction and urinary tract infection. [ABSTRACT FROM AUTHOR]

Summary: Background: Ustekinumab is effective in treating Crohn's disease (CD) and ulcerative colitis (UC). However, the loss of response (LOR) to ustekinumab and the efficacy of dose escalation have not been systematically explored. Methods: Databases were searched for eligible studies from inception through July 2021. Summary estimates were pooled, and subgroup analyses were performed to explore heterogeneity. Results: We included 14 studies (CD: 13; UC: 1). In CD patients, the annual risk of LOR to ustekinumab and dose escalation among primary responders was 21% (95% confidence interval [CI] 12–31%, 1530 person‐years, n = 9) per person‐year and 25% (95% CI 12–32%, 657 person‐years, n = 5) per person‐year respectively. Clinical response was regained in 58% (95% CI 49–67%, 279 patients, n = 8) of secondary non‐responders after dose escalation (interval reduction or intravenous reinduction). In UC patients, no studies provided data on LOR, but only one study showed that 35% (100/284) of patients underwent dose escalation (or sham dose adjustment), leading to an annual risk of dose escalation of 18% per person‐year. After dose escalation, 58% (14/24) of the patients regained symptomatic remission. Conclusions: Primary responders with CD experienced LOR to ustekinumab at a risk of 21% per person‐year and required dose escalation at a risk of 25% per person‐year. Fifty‐eight per cent of secondary non‐responders with CD may benefit from dose escalation. LOR has not been well characterized in patients with UC. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Thiopurine S‐methyltransferase (TPTM) is a well known biomarker for thiopurine‐induced leucopenia, which has limited value in Asia. Instead, NUDT15 C415T is a promising predictor in Asia. Aims: To explore whether an optimised strategy based on NUDT15 C415T genotypes affects thiopurine‐induced leucopenia, as well as efficacy in Chinese patients with Crohn's disease. Methods: Patients with Crohn's disease and indications for thiopurines were included from two hospitals in China. They were randomly assigned to either the intervention or the control group. In the intervention group, those with genotype CC received a standard dose (control group), those with CT genotype received 50% of the standard dose, those with TT genotype received alternative drugs. The primary endpoint was thiopurine‐induced leucopenia (<3.5 × 109/L). Secondary outcomes were the incidence of other adverse events and the efficacy for maintaining steroid‐free remission at week 36. Results: The rate of thiopurine‐induced leucopenia was lower in the intervention group (n = 52) than in the control group (n = 66) (23.7% vs 32.4%, P = 0.049, RR = 0.73, 95% CI 0.53‐1.00). In CT subgroup, the incidence of leucopenia in the intervention group (n = 10) was significantly lower than in the control group (n = 28) (31.3% vs 65.1%, RR = 0.48, 95% CI 0.28‐0.84). Neither other adverse events nor treatment efficacy was significantly different between the two groups during follow‐up. Conclusions: Among Chinese patients with Crohn's disease, dose optimisation by NUDT15 C415T reduced the rate of thiopurine‐induced leucopenia, without significant influence on efficacy. Using 50% dose reduction for heterozygotes, and alternative drugs for homozygotes, are practicable strategies. Clinical trial number: NCT02929706. [ABSTRACT FROM AUTHOR]

Background: Neural tube defect (NTD) is a common birth defect causing much death in the world. Variants in VANGL1 lead to NTD and caudal regression syndrome. NTD displays a complex phenotype encompassing both genetic and environmental factors. Methods: The fetus was diagnosed by prenatal ultrasound examination. Postnatal CT and autopsy were performed. Genetic testing was conducted in the family and Sanger sequencing was validated. Multiple prediction soft‐wares were used to predict the pathogenicity of the variant. Results: The VANGL1 gene variant c.1151C>G (P384R) was detected in a fetus diagnosed with tethered spinal cord and sacrococcygeal lipoma. The VANGL1 variant c.1151C>G (P384R) was reported in a Klippel‐Feil syndrome patient. The VANGL1 variant was validated in the trio‐family but the mother showed no abnormalities. Conclusion: Overall, this study presents fetal NTD caused by the same VANGL1 variant found in a Klippel‐Feil syndrome patient with complete clinical information of prenatal ultrasound, postnatal CT, and genetic results as early as 25 GW. Our study not only expands the VANGL1 mutational spectrum but also sheds light on the important role of the VANGL1 P384R variant in human development. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate cranial ultrasound markers during a first‐trimester routine ultrasound examination for screening for open spina bifida (OSB). Methods: Midsagittal and axial images of the fetal head obtained from fetuses with spina bifida and unaffected control fetuses at 11 weeks to 13 weeks 6 days were analyzed retrospectively. The observed markers of the posterior brain included the 4‐ versus 3‐line view, the brain stem (BS)‐to‐brain stem‐occipital bone (BSOB) distance ratio (BS/BSOB), the position relationship between the maxillo‐occipital (MO) line and the midbrain‐BS junction, and the crash sign status. Results: This study included 9 OSB cases, 2 closed spina bifida (CSB) cases, and 200 unaffected controls. Eight of 9 OSB cases had informative midsagittal views of the head. The 3‐line view (abnormal) and BS/BSOB greater than 1 (abnormal) were observed in 87.5% (7 of 8) and 100% (8 of 8), respectively. The midbrain‐BS junction was below or nearly on the MO line (abnormal) in 100% (8 of 8). Seven of the cases had informative axial views of the head. The crash sign (abnormal) was observed in 85.7% (6 of 7). A 3‐line view was seen in all of the cases that had a positive crash sign. Neither of the 2 cases of CSB and none of the controls had any of the 4 first‐trimester intracranial ultrasound markers of OSB. Conclusions: The 4 first‐trimester intracranial ultrasound markers investigated in this study appear to be very good markers of OSB, especially a BS/BSOB greater than 1 and an abnormal MO line. The crash sign and 3‐line view were observed in the same fetus. In our study, these ultrasound findings were not helpful in CSB. [ABSTRACT FROM AUTHOR]

To inform mitigation strategies and understand how microplastics affect wildlife, research is focused on understanding the sources, pathways, and occurrence of microplastics in the environment and in wildlife. Microplastics research entails counting and characterizing microplastics in nature, which is a labor‐intensive process, particularly given the range of particle sizes and morphologies present within this diverse class of contaminants. Thus, it is crucial to determine appropriate sampling methods that best capture the types and quantities of microplastics relevant to inform the questions and objectives at hand. It is also critical to follow protocols with strict quality assurance and quality control (QA/QC) measures so that results reflect accurate estimates of microplastic contamination. Here, we assess different sampling procedures and QA/QC strategies to inform best practices for future environmental monitoring and assessments of exposure. We compare microplastic abundance and characteristics in surface‐water samples collected using different methods (i.e., manta and bulk water) at the same sites, as well as duplicate samples for each method taken at the same site and approximate time. Samples were collected from 9 sampling sites within San Francisco Bay, California, USA, using 3 different sampling methods: 1) manta trawl (manta), 2) 1‐L grab (grab), and 3) 10‐L bulk water filtered in situ (pump). Bulk water sampling methods (both grab and pump) captured more microplastics within the smaller size range (<335 µm), most of which were fibers. Manta samples captured a greater diversity of morphologies but underestimated smaller‐sized particles. Inspection of pump samples revealed high numbers of particles from procedural contamination, stressing the need for robust QA/QC, including sampling and analyzing laboratory blanks, field blanks, and duplicates. Choosing the appropriate sampling method, combined with rigorous, standardized QA/QC practices, is essential for the future of microplastics research in marine and freshwater ecosystems. Integr Environ Assess Manag 2021;17:282–291. © 2020 SETAC KEY POINTS: It is critical to determine appropriate sampling methods that best capture the types and quantities of microplastics relevant to inform the questions and objectives at hand.Adhering to protocols with strict quality assurance and quality control (QA/QC) measures ensures that results reflect accurate estimates of microplastic contamination.Taking duplicate samples can reveal the variability between samples at a single site.Manta samples capture a greater diversity of morphologies than do grab samples, but they underestimate smaller‐sized particles. [ABSTRACT FROM AUTHOR]

The article offers information on several aspects of microplastics. Topics discussed include information on the analysis of microplastics in terms of different sizes, shapes, colors, and types of materials; views on the impact of microplastics in marine and terrestrial ecosystems; and information on methods for sampling and quantifying microplastics.

3‐Chloro‐4‐methylphenylcarbamate‐(3‐(2‐O‐β‐cyclodextrin)‐2‐hydroxypropoxy)‐propylsilyl‐appended silica particles (CMP‐CD‐HPS), a new type of partially‐substituted cyclodextrin‐bonded phase, have been successfully synthesized and applied as a chiral stationary phase in high‐performance liquid chromatography under multi‐mode conditions including normal phase, reversed phase, and polar organic mobile phase conditions. Chemical characterization for the CMP‐CD‐HPS was carried out by elemental analysis. The chromatographic performance of CMP‐CD‐HPS‐packed column was evaluated by separating the positional isomers of nitrophenol and nitraniline and the enantiomers of some chiral drug compounds. The separation results show that CMP‐CD‐HPS exhibited excellent selectivity for separating the positional isomers of disubstituted benzenes and the enantiomers of the chiral drugs. The hydroxyl residues of partially‐substituted β‐cyclodextrin and the stable spacer linking to secondary hydroxyl site of the β‐cyclodextrin in the new CMP‐CD‐HPS phase play important roles in the chromatographic separations. [ABSTRACT FROM AUTHOR]

Summary: Background: Major depressive disorder (MDD) is a mental disease characterized by depressed mood, lifetime anxiety, and deficits of learning and memory. Inhibition of phosphodiesterase 9 (PDE9) has been reported to improve rodent cognitive and memory function. However, the role of PDE9 in MDD, in particular its manifestations of depression and anxiety, has not been investigated. Methods: We examined the protective effects of WYQ‐C36D (C36D), a novel PDE9 inhibitor, against corticosterone‐induced cytotoxicity, pCREB/CREB and BDNF expression by cell viability, and immunoblot assays in HT‐22 cells. The potential effects of C36D at doses of 0.1, 0.5, and 1 mg/kg on stress‐induced depression‐ and anxiety‐like behaviors and memory deficits were also examined in mice. Results: C36D significantly protected HT‐22 cells against corticosterone‐induced cytotoxicity and rescued corticosterone‐induced decreases in cGMP, CREB phosphorylation, and BDNF expression. All these effects were otherwise blocked by the PKG inhibitor Rp‐8‐Br‐PET‐cGMPS (Rp8). In addition, when tested in vivo in stressed mice, C36D produced antidepressant‐like effects on behavior, as shown by decreased immobility time both in the forced swimming and tail suspension tests. C36D also showed anxiolytic‐like and memory‐enhancing effects in the elevated plus‐maze and novel object recognition tests. Conclusion: Our results show that inhibition of PDE9 by C36D produces antidepressant‐ and anxiolytic‐like behavioral effects and memory enhancement by activating cGMP/PKG signaling pathway. PDE9 inhibitors may have the potential as a novel class of drug to treat MDD. [ABSTRACT FROM AUTHOR]

Summary: Aims: Depression is currently the most common mood disorder. Regulation of intracellular cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) signaling by phosphodiesterase (PDE) inhibition has been paid much attention for treatment of depression. This study aimed to investigate the neuroprotective effects of Hcyb1, a novel PDE2 inhibitor, in HT‐22 cells and antidepressant‐like effects in mouse models of depression. Methods: Hcyb1 was synthesized and its selectivity upon PDE2 was tested. Moreover, HT‐22 hippocampal cells were used to determine the effects of Hcyb1 on cell viability, cyclic nucleotide levels, and the downstream molecules related to cAMP/cGMP signaling by neurochemical, enzyme‐linked immunosorbent, and immunoblot assays in vitro. The antidepressant‐like effects of Hcyb1 were also determined in the forced swimming and tail suspension tests in mice. Results: Hcyb1 had a highly selective inhibition of PDE2A (IC50 = 0.57 ± 0.03 μmol/L) and over 250‐fold selectivity against other recombinant PDE family members. Hcyb1 at concentrations of 10−10 and 10−9 mol/L significantly increased cell viability after treatment for 24 hours. At concentrations of 10−9~10−7 mol/L, Hcyb1 also increased cGMP levels by 1.7~2.3 folds after 10‐minute treatment. Furthermore, Hcyb1 at the concentrations of 10−9 mol/L increased both cGMP and cAMP levels 24 hours after treatment. The levels of phosphorylation of CREB and BDNF were also increased by Hcyb1 treatment in HT‐22 cells for 24 hours. Finally, in the in vivo tests, Hcyb1 (0.5, 1, and 2 mg/kg, i.g.) decreased the immobility time in both forced swimming and tail suspension tests, without altering locomotor activity. Conclusion: These results suggest that the novel PDE2 inhibitor Hcyb1 produced neuroprotective and antidepressant‐like effects most likely mediated by cAMP/cGMP‐CREB‐BDNF signaling. [ABSTRACT FROM AUTHOR]

Abstract: The mechanism of the Ni0‐catalyzed reductive carboxylation reaction of C(sp2)−O and C(sp3)−O bonds in aromatic esters with CO2 to access valuable carboxylic acids was comprehensively studied by using DFT calculations. Computational results revealed that this transformation was composed of several key steps: C−O bond cleavage, reductive elimination, and/or CO2 insertion. Of these steps, C−O bond cleavage was found to be rate‐determining, and it occurred through either oxidative addition to form a NiII intermediate, or a radical pathway that involved a bimetallic species to generate two NiI species through homolytic dissociation of the C−O bond. DFT calculations revealed that the oxidative addition step was preferred in the reductive carboxylation reactions of C(sp2)−O and C(sp3)−O bonds in substrates with extended π systems. In contrast, oxidative addition was highly disfavored when traceless directing groups were involved in the reductive coupling of substrates without extended π systems. In such cases, the presence of traceless directing groups allowed for docking of a second Ni0 catalyst, and the reactions proceed through a bimetallic radical pathway, rather than through concerted oxidative addition, to afford two NiI species both kinetically and thermodynamically. These theoretical mechanistic insights into the reductive carboxylation reactions of C−O bonds were also employed to investigate several experimentally observed phenomena, including ligand‐dependent reactivity and site‐selectivity. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Chao et al papers. To view these articles, visit https://doi.org/10.1111/apt.16600 and https://doi.org/10.1111/apt.16719 [ABSTRACT FROM AUTHOR]

This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and α-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-кB. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This report explores some properties of 80-200 nm nanoparticles containing 5-aminolevulinic acid ( ALA) and fullerene (C60) for photodynamic therapy (PDT). Compared with ALA, the nanoparticles yielded more protoporphyrin IX (Pp IX) formation in cells and tissues and to a significant improvement in antitumor efficacy in tumor-bearing mice. Maximum levels of Pp IX were obtained 4 h after administration and selective Pp IX formation in tumor was observed. These nanoparticles appear to be a useful vehicle for drug delivery purposes. In this study, a procedure for preparing fullerene nanoparticles containing ALA was developed. The product alone exhibited no detectable toxicity in the dark and was superior to ALA alone in promoting Pp IX biosynthesis and PDT efficacy both in culture and in a murine tumor model. These results suggest that this procedure could be the basis for an improved PDT protocol for cancer control. [ABSTRACT FROM AUTHOR]

Pulmonary arteriovenous fistula or malformation (PAVM) is a relatively rare condition associated with hereditary hemorrhagic telangiectasia (HHT).1 HHT is an autosomal dominant genetic disorder with abnormal vascular development.2 Few cases of HHT are de novo.3 PAVM is extremely rare in fetuses.4 Here we characterized a PAVM fetus with antenatal ultrasound, postnatal magnetic resonance imaging (MRI) and genetic outcome. This study introduced a novel de novo mutation of I ENG i gene presenting as PAVM at prenatal diagnosis. Most pathogenic/likely pathogenic mutations of the I ENG i gene were frameshift and nonsense mutation causing intracerebral and pulmonary AVMs. [Extracted from the article]

Aim: The accuracy of liver stiffness measurement (LSM) in the diagnosis of liver fibrosis is affected by elevated serum alanine aminotransferase (ALT) levels. The aim of this study was to assess the impact of mild to moderate elevations of ALT on LSM in patients with chronic hepatitis B (CHB) during antiviral therapy. Methods: A total of 58 CHB patients with their ALT levels falling into the range of ×2 to ×10 the upper limit of normal (ULN) were recruited. ALT and LSM values were periodically assessed at baseline and 12, 24 and 48 weeks. Results: The median ALT levels were 153.5 (76-544), 50.5 (11-475), 36.5 (9-265) and 30 (12-239) IU/L at baseline and 12, 24 and 48 weeks, respectively. The corresponding median value of LSM was 8.8 (3.2-47.3), 6.15 (3.2-31.2), 5.9 (3.1-29.1) and 5.5 (2.8-21.5) kpa. However, after the ALT levels were normalized by the treatment, the values of LSM did not vary significantly (6.1 [3.0-17.7] vs 5.25 [2.8-21.5] kpa, P = 0.381). Pretreatment fibrosis stages of liver biopsies corresponded with LSM after ALT normalization rather than baseline LSM (F0-1, 12/27 vs 23/25, P < 0.001). Conclusion: The LSM values decreased in parallel with the decline in ALT levels in CHB patients with mild to moderate elevation of ALT. LSM became more accurate when applied to document the liver fibrosis or cirrhosis in CHB patients after the elevated ALT level has been treated to normal level. [ABSTRACT FROM AUTHOR]

Recent years have seen a growing body of evidence showing that plant competition and facilitation usually operate simultaneously to drive population dynamics, community structure and ecosystem functions. However, the potential role of facilitation in spatial patterning of plant populations has rarely been explicitly examined. We used a 'zone-of-influence' model to explore how facilitation interacts with competition and abiotic stress to determine the spatial patterning of populations during density-dependent mortality. Model simulations revealed that started with the same clustered pattern, the final pattern of simulated populations depended strongly on the interaction among facilitation, stress level and size-symmetry of competition. Asymmetric competition consistently led to immediate and non-random mortality towards regularity, thus rapidly decayed the initially clustered pattern to final patterns of small-scale regularity and large-scale randomness. The role of symmetric competition in decaying the clustered pattern increased with abiotic stress because stress-induced reductions in plants' growth rates can make individuals in high-density clusters more likely to die even from symmetric competition. Facilitation played a clear role in counteracting the effect of stress, thus tended to maintain the degree of clustering of the pattern during density-dependent mortality. This is because the amelioration of harsh conditions by neighboring plants relieved the reductions in plant growth due to competition, thus slowed down and reduced the mortality inside clusters (relative to that outside clusters). Moreover, the effect of facilitation appeared to increase with abiotic stress. Our results indicate that facilitation among neighboring plants should partially be responsible for clustered population spatial patterns observed in stressful environments, even though its contribution relative to other factors (e.g. local dispersal and environmental heterogeneity) remains to be evaluated. In addition, the potential influence of facilitation on self-thinning trajectory should be explicitly examined in future modeling and experimental studies considering its effects on density-dependent mortality. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the synthesis and electrorheological properties of polyaniline-coated barium titanate composite particles. It mentioned how the structure of composite particles was characterized. It found that the composite particles-based electrorheological fluids (ERFs) have lower field-off viscosity due to the molecular interaction.

GLO:FU4V/01jul21:mgg31778-toc-0001.jpg PHOTO (COLOR): . gl The cover image is based on the Clinical Report I The VANGL1 P384R variant cause both neural tube defect and Klippel-Feil syndrome i by Chen Cheng et al., https://doi.org/10.1002/mgg3.1710. [Extracted from the article]

In this paper, we explore the consequences of using link travel time estimates with high variance to compute the minimum travel time route between an origin and destination pair. Because of platoon formation or for other reasons, vehicles on a link separated by small headways tend to have similar travel times. In other words, the covariance of link travel times of distinct vehicles which are close together may not be zero. It follows that the variance of the mean of travel times obtained from a sample of n vehicles on a same link over small time intervals is of the form a + b / n where a and b would usually be positive. This result has an important implication for the quality of road network travel time information given by Intelligent Transportation Systems (ITS)—that the variance of the estimate of mean travel time does not go to zero with increasing n . Thus the quality of information disseminated by ITS is not necessarily improved by increasing the market penetration of vehicles monitoring the system with the necessary equipment (termed probe vehicles). Estimates of a and b for a set of links are presented in the paper and consequences for probe-based ITS are explored by means of a simulation of such a system which is operational on an actual network. [ABSTRACT FROM AUTHOR]

The preventive effect of Hydrolyzed Rice Bran against the common cold syndrome was examined in elderly people. Arabinoxylan derivatives of Hydrolyzed Rice Bran (HRB) were prepared from water-soluble rice bran through partial processing using a carbohydrate complex. Using the water-soluble Rice Bran (RB) as a control, a cross over double-blind study was conducted on both substances over a 6-week administration period. Fifty elderly people aged from 70 to 95 years participated in the study and the comparative data from 36 participants were analyzed. There were no withdrawals from in the study due to the side effects of the experimental foods. Symptoms were observed and scored. The total symptom score for the RB treatment group was three times higher than that for the HRB treatment group. The average duration of symptoms was 2.6 days for RB whereas it was only 1.2 days for HRB. Furthermore, some immunomodulatory action was observed in laboratory tests. HRB was shown to be useful in reducing the physical stress associated with acute respiratory tract infection. [ABSTRACT FROM AUTHOR]

Describes the infinite double-stranded chain polymer catena-poly[[bis(dicyanamido)zinc(II)]-di-μ-1,2-bis(1,2,4-triazol-1-yl) ethane-κ[sup 4]N[sup 4]:N[sup 4']]. Polymeric structure of the compound with 18-membered spiro-fused rings extending in the b direction and each 18-membered ring involving two inversion-related bte molecules.

An abstract of the conference paper "Clinical combining-application of ultrasound and MRI on multiplets malformations," by A. Xin Lin Chen, and colleagues is presented.

An abstract of the conference paper "Clinical value of contrast-enhanced ultrasonography on detecting placenta accrete, placenta increta and placenta percreta," by B. Chao Sheng and colleagues is presented.

The centrosymmetric dimeric title complex, [Zn(2)Br(4)(C(4)H(8)N(4))(2)], is isotypic with its [Zn(2)Cl(4)(C(4)H(8)N(4))(2)], [Zn(2)I(4)(C(4)H(8)N(4))(2)] and [Co(2)Cl(4)(C(4)H(8)N(4))(2)] analogues. The zinc atom is bonded to two N atoms belonging to triazole bridging rings and to two terminal bromide ligands, in a geometry close to tetra-hedral. Weak N-H⋯Br hydrogen bonds, with the amine functions as donor groups, are observed in the crystal structure, forming a three-dimensional supra-molecular network.

The Co(II) atom in the title complex, [Co(NO(2))(2)(C(12)H(12)N(6))(2)](n), lies on an inversion center and is coordinated by four N atoms from the triazole rings of two symmetry-related pairs of 1,4-bis-(1,2,4-triazol-1-ylmeth-yl)benzene (bbtz) ligands and two O atoms from two symmetry-related monodentate nitrate ligands in a distorted octa-hedral geometry. The Co atoms are bridged by four bbtz ligands, forming a two-dimensional (4,4) network parallel to (102).

The coordination geometry of the Cd(II) atom in the title complex, [Cd(NCO)(2)(C(10)H(14)N(4))(2)](n) or [Cd(NCO)(2)(bimb)(2)](n), where bimb is 1,4-bis-(imidazol-1-yl)butane, is distorted octa-hedral with the Cd(II) atom located on an inversion center and connected to four N atoms from the imidazole units of four symmetry-related bimb ligands and two O atoms from two symmetry-related NCO(-) ligands. The Cd(II) atoms are bridged by four bimb ligands, forming a two-dimensional (4,4) network.

This his article reports the findings of a study conducted to investigate the personality types of Chinese dental school applicants. The Chinese version of the Myers-Briggs Type Indicator (MBTI) (Form G) was used to assess the personality styles of 332 dental school applicants from the mainland of China. The results of the MBTI for Chinese dental school applicants were compared with a previous study of applicants from the U.K. A higher percentage of this group of Chinese applicants scored higher for Introversion (I) than Extroversion (E); both Chinese and English applicants preferred Judging (J) to Perceiving (P). The dominant personality types in Chinese applicants were ISTJ, ESTJ, and ISFP. The findings suggest that the personality types of Chinese dental students may be somewhat different from the personality profiles exhibited by dental students from other nations. The findings may be of value to individuals who desire to investigate personality type differences among dental students with different cultural backgrounds.