This work presents a molecular dynamics (MD) simulation study on the effect of grain boundaries (GBs) on the mechanical properties of epoxy/graphene composites. Ten types of GB models were ...constructed and comparisons were made for epoxy/graphene composites containing graphene with GBs. The results showed that the tensile and compressive behaviors, the glass transition temperature (
), and the configurations of epoxy/graphene composites were significantly affected by GBs. The tensile yield strength of epoxy/graphene composites could be either enhanced or weakened by GBs under a tensile load parallel to the graphene sheet. The underlying mechanisms may be attributed to multi-factor coupling, including the tensile strength of the reinforcements, the interfacial interaction energy, and the inflection degree of reinforcements. A balance exists among these effect factors, resulting in the diversity in the tensile yield strength of epoxy/graphene composites. The compressive yield strength for epoxy/graphene composites is higher than their counterpart in tension. The tensile/compressive yield strength for the same configuration presents diversity in different directions. Both an excellent interfacial interaction and the appropriate inflection degree of wrinkles for GB configurations restrict the translational and rotational movements of epoxy chains during volume expansion, which eventually improves the overall
. Understanding the reinforcing mechanism for graphene with GBs from the atomistic level provides new physical insights to material design for epoxy-based composites containing defective reinforcements.
Recently, with the rapid progress of metagenomic next-generation sequencing (mNGS), inconsistency between mNGS results and clinical diagnoses has become more common. There is currently no reasonable ...explanation for this, and the interpretation of mNGS reports still needs to be standardised. A retrospective analysis was conducted on 47 inpatients with suspected central nervous system (CNS) infections, and clinical data were recorded. The final diagnosis was determined by an expert group based on the patient's clinical manifestation, laboratory examination, and response to treatment. mNGS results were compared with the final diagnosis, and any inconsistencies that occurred were investigated. Finally, the credibility of mNGS results was evaluated using the integral approach, which consists of three parts: typical clinical features, positive results with the traditional method, and cerebrospinal fluid cells greater than or equal to 100 (x 10.sup.6/L) or protein greater than or equal to 500 mg/L, with one point for each item. Forty-one patients with suspected CNS infection were assigned to infected (ID, 31/41, 75.61%) and non-infected groups (NID, 10/41, 24.39%) after assessment by a panel of experts according to the composite diagnostic criteria. For mNGS-positive results, 20 of the 24 pathogens were regarded as contaminants when the final score was less than or equai to 1. The remaining 11 pathogens detected by mNGS were all true positives, which was consistent with the clinical diagnosis when the score was greater than or equal to 2. For mNGS negative results, when the score was greater than or equal to 2, the likelihood of infection may be greater than when the score is less than or equai to 1. The integral method is effective for evaluating mNGS results. Regardless of whether the mNGS result was positive or negative, the possibility of infection was greater when the score was greater than or equal to 2. A negative mNGS result does not necessarily indicate that the patient was not clinically infected, and, therefore, clinical features are more important.
The cytotoxic effects of thirteen triterpene glycosides from Holothuria scabra Jaeger and Cucumaria frondosa Gunnerus (Holothuroidea) against four human cell lines were detected and their ...cytotoxicity-structure relationships were established. The apoptosis-inducing activity of a more potent glycoside echinoside A (1) in HepG2 cells was further investigated by determining its effect on the morphology, mitochondrial transmembrane potential (Δψm) and mRNA expression levels of the apoptosis-related genes. The results showed that the number of glycosyl residues in sugar chains and the side chain of aglycone could affect their cytotoxicity towards tumor cells and selective cytotoxicity. 1 significantly inhibited cell viability and induced apoptosis in HepG2 cells. 1 also markedly decreased the Δψm and Bcl-2/Bax mRNA express ratio, and up-regulated the mRNA expression levels of Caspase-3, Caspase-8 and Caspase-9 in HepG2 cells. Therefore, 1 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathway. These findings could potentially promote the usage of these glycosides as leading compounds for developing new antitumor drugs.
Using self-assembly gold nanoislands (SAM-AuNIs) functionalized by poly(m-phenylenediamine-co-aniline-2-sulfonic acid) (poly(mPD-co-ASA)) copolymer nanoparticles as specific receptors, a highly ...sensitive localized surface plasmon resonance (LSPR) optochemical sensor is demonstrated for detection of trace lead cation (Pb(II)) in drinking water. The copolymer receptor is optimized in three aspects: (1) mole ratio of mPD:ASA monomers, (2) size of copolymer nanoparticles, and (3) surface density of the copolymer. It is shown that the 95:5 (mPD:ASA mole ratio) copolymer with size less than 100 nm exhibits the best Pb(II)-sensing performance, and the 200 times diluted standard copolymer solution contributes to the most effective functionalization protocol. The resulting poly(mPD-co-ASA)-functionalized LSPR sensor attains the detection limit to 0.011 ppb toward Pb(II) in drinking water, and the linear dynamic range covers 0.011 to 5000 ppb (i.e., 6 orders of magnitude). In addition, the sensing system exhibits robust selectivity to Pb(II) in the presence of other metallic cations as well as common anions. The proposed functional copolymer functionalized on AuNIs is found to provide excellent Pb(II)-sensing performance using simple LSPR instrumentation for rapid drinking-water inspection.
Peritonitis caused by nontuberculous mycobacteria (NTM) is an infrequent but important complication in patients undergoing peritoneal dialysis (PD). There has been no report of mixed infections with ...multiple NTM. Peritoneal dialysis-associated peritonitis (PDAP) caused by Mycobacterium abscessus is more common than that caused by M. smegmatis and M. goodii.
This case concerns a patient with PDAP caused by gram-positive bacilli, which could not be identified at the species level in successive detections of initial peritoneal effluent. Later, M. smegmatis was detected with no sensitivity results in bacterial culture. However, metagenomic next-generation sequencing (mNGS) and first whole-genome sequences indicated that there were three species coexisting in the culture, including M. smegmatis (24,708 reads), M. abscessus (9224 reads), and M. goodii (8305 reads). This is the first case of PDAP with specific evidence that conventional detection methods isolated a poorly pathogenic NTM, whereas mNGS and first whole-genome sequences identified multiple NTM. Pathogenic bacteria might not be detected using conventional methods due to their lower abundance. This case report is the first description of mixed infections with more than two species of NTM during PDAP.
PDAP caused by multiple NTM is rare, and the diagnosis is difficult. When NTM are isolated by conventional tests in patients who are suspected of infection, clinicians should be vigilant, and further tests should be performed to determine the presence of rare or even previously unknown bacteria, for which the quantity is relatively low, but the pathogenicity is high. The rare pathogen may be a primary agent in causing such complications.
Prenatal exposure to ambient fine particles (diameter < 0.25 μm, PM2.5) has been found to be associated with abnormal growth and development in offspring. However, the effects of PM2.5 on the lipid ...metabolism of adipose tissue in offspring are unclear. In the present study, we established a mouse model of prenatal exposure to PM2.5 by intratracheal instillation to pregnant C57BL/6 female mice with PM2.5 suspension or normal saline. We found that prenatal exposure to PM2.5 of a mouse model reduced body weight in adult male offspring after 6 weeks old. Histological analysis showed that the adipocyte size was significantly reduced in epididymal adipose tissue (eWAT) in male offspring, but not in brown adipose tissue. The expression levels of genes related to fatty acid synthesis (ACC1, ACSL1) and oxidation (PPARα) in eWAT were also significantly decreased. In addition, downregulation of pro-inflammatory cytokines (TNFα, IL-1β, IL-6) was also observed. Lipidomics analysis of eWAT demonstrated that prenatal exposure of PM2.5 reduced lysophosphatidylcholines (LPC), phosphatidylcholines (PC), phosphatidylethanolamines (PE), sphingomyelins (SM), and ceramides (Cer), indicating that metabolic pathways, including SM-Cer signaling and glycerophospholipids remodeling, were disrupted. In summary, prenatal exposure to PM2.5 was associated with the dysregulations in lipid metabolism of eWAT and pro-inflammatory response in male offspring.
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•Prenatal exposure to PM2.5 reduced adipocyte size of eWAT in male offspring.•The decreasing levels of pro-inflammatory cytokines were found in adipose tissue.•The expression of genes involved in fatty acid synthesis and oxidation were reduced.•A disrupted metabolism of lipids was found in adipose tissue.
Objective
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Chong Xie, Xiangfeng Chen, and Yulin Liu contributed equally to this work.
Genetic defects are identified in nearly 20% of infertile males. Determining the frequency and types of major ...genetic abnormalities in severe male infertility helps inform appropriate genetic counseling before assisted reproductive techniques.
Methods
Cytogenetic results of 912 patients with non-obstructive azoospermia (NOA) and severe oligozoospermia (SOS) in Eastern China were reviewed in this multicenter study from January 2011 to December 2015. Controls were 215 normozoospermic men with offspring.
Results
Among all patients, 22.6% (206/912) had genetic abnormalities, including 27.3% (146/534) of NOA patients and 15.9% (60/378) of SOS patients. Chromosomal abnormalities (all autosomal) were detected in only 1.9% (4 /215) of controls. In NOA patients, sex chromosomal abnormalities were identified in 25.8% (138/534), of which 8% (43/534) had a 47,XXY karyotype or its mosaic; higher than the SOS group prevalence (1.1%; 4/378). The incidence of Y chromosome microdeletions was lower in the SOS group (13.2%; 50/378) than in the NOA group (17.8%; 95/534).
Conclusions
The high prevalence of genetic abnormalities in our study indicates the importance of routine genetic testing in severe male infertility diagnosis. This may help determine the choice of assisted reproductive technique and allow specific pre-implantation genetic testing to minimize the risk of transmitting genetic defects.
Covalent organic nanospheres (CONs) were explored as a fiber coating for solid-phase microextraction of genotoxic impurities (GTIs) from active ingredients (AIs). CONs were synthesized by an easy ...solution-phase procedure at 25 °C. The obtained nanospheres exhibited a high specific surface area, good thermostability, high acid and alkali resistance, and favorable crystallinity and porosity. Two types of GTIs, alkyl halides (1-iodooctane, 1-chlorobenzene, 1-bromododecane, 1,2-dichlorobenzene, 1-bromooctane, 1-chlorohexane, and 1,8-dibromooctane) and sulfonate esters (methyl p-toluenesulfonate and ethyl p-toluenesulfonate), were chosen as target molecules for assessing the performance of the coating. The prepared coating achieved high enhancement factors (5097–9799) for the selected GTIs. The strong affinity between CONs and GTIs was tentatively attributed to π–π and hydrophobicity interactions, large surface area of the CONs, and size-matching of the materials. Combined with gas chromatography-mass spectrometry (GC-MS), the established analytical method detected the GTIs in capecitabine and imatinib mesylate samples over a wide linear range (0.2–200 ng/g) with a low detection limit (0.04–2.0 ng/g), satisfactory recovery (80.03%–109.5%), and high repeatability (6.20%–14.8%) and reproducibility (6.20%–14.1%). Therefore, the CON-coated fibers are promising alternatives for the sensitive detection of GTIs in AI samples.
Schematic presentation of fabrication for covalent organic nanospheres via schiff base reaction at room temperature. Then, they were used for ultrasensitive solid-phase microextraction of genotoxic impurities prior to gas chromatography mass spectrometry. Display omitted
•CONs were synthesized and characterized.•CONs were used as sorbents for SPME.•An SPME-GC/MS method was developed for GTI analysis.•This method was successfully applied to GTI analysis of pharmaceutical samples.
For a long time, people have suffered from uncertainty, complexity, and a low success rate in generating and screening antibodies against small molecules, which have become the core bottlenecks of ...immunochemistry. Here, the influence of antigen preparation on antibody generation was investigated at both molecular and submolecular levels. Neoepitopes (amide-containing neoepitopes) formed in the preparation of complete antigens are one of the most important factors limiting the efficiency of generating hapten-specific antibodies, which was verified by different haptens, carrier proteins, and conjugation conditions. Amide-containing neoepitopes present electron-dense structural components on the surface of prepared complete antigens and, therefore, induce the generation of the corresponding antibody with much higher efficiency than target hapten. Crosslinkers should be carefully selected and not overdosed. According to these results, some misconceptions in the conventional anti-hapten antibody production were clarified and corrected. By controlling the content of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) during the synthesis of immunogen to limit the formation of amide-containing neoepitopes, the efficiency of hapten-specific antibody generation could be significantly improved, which verified the correctness of the conclusion and provided an efficient strategy for antibody preparation. The result of the work is of scientific significance in the preparation of high-quality antibodies against small molecules.
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