Multivalent cooperativity plays an important role in the supramolecular self-assembly process. Herein, we report a remarkable cooperative enhancement of both structural integrity and metal ion ...selectivity on metal-organic M
L
tetrahedral cages self-assembled from a tris-tridentate ligand (L
) with a variety of metal ions spanning across the periodic table, including alkaline earth (Ca
), transition (Cd
), and all the lanthanide (Ln
) metal ions. All these M
L
cages are stable to excess metal ions and ligands, which is in sharp contrast with the tridentate (L
) ligand and bis-tridentate (L
) ligand bearing the same coordination motif as L
. Moreover, high-precision metal ion self-sorting is observed during the mixed-metal self-assembly of tetrahedral M
L
cages, but not on the M
L
counterparts. Based on the strong cooperative metal ion self-recognition behavior of M
L
cages, a supramolecular approach to lanthanide separation is demonstrated, offering a new design principle of next-generation extractants for highly efficient lanthanide separation.
Lariciresinol (LA) is one of the main active ingredients in many traditional medicinal plants such as Patrinia, and has the role of anti-liver cancer. However, the precise mechanisms are unclear. ...This study investigated the molecular mechanisms of LA against HepG2 cells. LA anti-tumor activity was assessed with the CCK-8, Ki-67, and immunofluorescence staining. Cells apoptotic ratio was evaluated by Annexin V/PI double-staining assay. A proteomic approach was used to identify differentially expressed proteins after LA treatment. JC-1 staining was carried out to detect the mitochondrial membrane potential (ΔΨm), and the Western blot analysis was used to analyse the apoptosis-associated proteins. Our results suggested that LA significantly suppressed the viability of HepG2 cells. The CCK-8 and Ki-67 expression indicated dose-dependent decreases in cell proliferation. Flow cytometry analysis showed that LA exhibited a apoptosis-inducing effect. The proteomic study observed the presence of apoptosis-associated proteins and mitochondrial dysfunction in HepG2 cells after LA-treatment. Further analysis showed that LA could trigger the mitochondrial-mediated apoptosis pathway, based on a decrease in ΔΨm; deliver of cytochrome c; activation of caspase-9/−3 and poly(ADP-ribose) polymerase; and decrease of the proportion of Bcl-2/Bax. Collectively, our studies found that LA exhibits significant cytotoxic effects by inhibiting cell proliferation, inducing apoptosis, possibly via activation of the mitochondrial-mediated apoptosis pathway.
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To evaluate the effect of SMU.2055 gene on acid resistance of Streptococcus mutans.
A SMU.2055-dificient mutant strain of S. mutans was constructed using homologous recombination technique. The ...growth of the wild-type and mutant strains was monitored in both normal and acidic conditions. The lethal pH level, glycolysis, proton permeability, cell permeability and biofilm formation of the two strains were compared.
PCR and sequence analyses verified the successful construction of the SMU.2055-dificient mutant strain. The growth and biofilm formation capacity of the mutant strain were obviously lowered in both normal and acidic conditions. The mutant strain also showed increased lethal pH level, proton permeability, and cell permeability with impaired H
-ATPase activity in acidic conditions, but its minimum glycolytic pH remained unaffected.
The SMU.2055-deficient S. mutans mutant exhibits a lowered acid resistance, which affects the growth, lethal pH, proton permeability, H
-ATPase activity, cell permeability a
To construct a SMU.2055-dificient mutant strain of Streptococcus mutans (S. mutans) and evaluate its cariogenic capacity in comparison with wild-type S. mutans.
The SMU.2055-dificient mutant strain ...of S. mutans was constructed using homologous recombination technique and observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The absorbance at 600 nm and pH values of the wild-type and mutant strains were monitored to evaluate their growth and acid production. After acid adaption, the two strains were challenged with acid shock and their survival rates were determined.
PCR and sequence analyses verified the successful construction of the SMU.2055-dificient mutant strain. Observation with SEM revealed obvious changes in the morphology of the mutant strain, which showed reduced irregular substances between the individual bacteria as compared with the wild-type strain. TEM revealed major alterations in the cellular architecture of the mutant strain with blurry cell membrane an
Although rabies virus is widely distributed in the world, and has been the subject of extensive investigations with the objective of its ultimate prevention, control, and management, there is much ...less knowledge of the characteristics, distribution, and infectivity of other lyssaviruses. Since bats are known animal vectors for all but one of the known lyssavirus genotypes, we have performed an extensive survey of bats in the Guangxi Province to provide information on lyssavirus distribution in southern China. The lyssavirus nucleoprotein gene was detected in brains of 2.86 % of 2,969 bats. Nucleotide sequence homologies among isolates were 86.9–99.6 %, but only 70.0–85.0 % for lyssaviruses in GenBank. These infected bats were detected from a wide area, essentially forming a band running from the south-west to the north-east of Guangxi, and it appears that infection by new lyssaviruses is widespread in this region.
A series of matrix reference materials for 21 inorganic trace impurities in 2 mg/g cadmium telluride (CdTe) solution with five impurity concentration levels (0, 1, 2, 4, 8 ng/g) were developed. High ...purity (>99.999%) CdTe was used as raw materials and dissolved using HCl-HNO3 mixed acid, and then was doped with multi-elements solutions to prepare the candidate reference materials (RMs). Matrix-matched ICP-MS with internal standard calibration was established for certification, homogeneity test and stability test. Mass spectrum interferences of 106Cd1H on 107Ag and 114In1H on 115In could be effectively removed by optimizing argon gas flow parameters coupled with mathematical correction. The matrix suppressed effect was effectively corrected about 20%-60% by using matrix-matched method. The precision of consecutive analysis expressed as RSD (n=22) was reduced to approximately 1% by using internal standard calibration. The linearly correlation coefficient factors (R) of standard curves were greater than 0.999 for all elements. The limits of detection (LODs) ranged from 0.001 ng/g to 0.35 ng/g, and the spike recoveries ranged from 89.2% to 106.5%. The established method was further validated by using CRM EB507. The dissolution of packaging containers was investigated and the results showed that the impurity dissolution from HDPE (high density polyethylene) bottle was lower than that from PP (polypropylene) plastic bottle. Except for Ca and Se, the dissolution of elements of concern in 4 months was less than 0.2 ng/g, which met the requirement. All elements were tested by the established method, and the results showed that the homogeneity, long-term and short-term stability of RMs were satisfactory and the validity period was 12 months. The mass fractions of 21 elements were certified by using a collaborative characterization program with eight sophisticated participating laboratories and using HR-ICP-MS and Q-ICP-MS methods. The arithmetic mean values were taken as the certified values, and the uncertainty was systematically and comprehensively evaluated. The measured results ranged from 3.5 ng/g to 4.5 ng/g, and the RSD ranged from 1.2% to 8.5% from 8 labs. The average value was about 4.0 ng/g, which was consistent with the target values and the relative expanded uncertainty was about 7%. This series of matrix RMs fills the blank of relevant RMs at home and abroad, and it plays an important role in verifying the reliability of measurement methods and ensuring the consistency and traceability of measurement results.
Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral ...organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose at resectable stage. Recent studies have suggested that extracellular vesicles (EVs) contain long RNAs. The aim of this study was to ...develop a diagnostic (d-)signature for the detection of PDAC based on EV long RNA (exLR) profiling.
We conducted a case-control study with 501 participants, including 284 patients with PDAC, 100 patients with chronic pancreatitis (CP) and 117 healthy subjects. The exLR profile of plasma samples was analysed by exLR sequencing. The d-signature was identified using a support vector machine algorithm and a training cohort (n=188) and was validated using an internal validation cohort (n=135) and an external validation cohort (n=178).
We developed a d-signature that comprised eight exLRs, including FGA, KRT19, HIST1H2BK, ITIH2, MARCH2, CLDN1, MAL2 and TIMP1, for PDAC detection. The d-signature showed high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.960, 0.950 and 0.936 in the training, internal validation and external validation cohort, respectively. The d-signature was able to identify resectable stage I/II cancer with an AUC of 0.949 in the combined three cohorts. In addition, the d-signature showed superior performance to carbohydrate antigen 19-9 in distinguishing PDAC from CP (AUC 0.931 vs 0.873, p=0.028).
This study is the first to characterise the plasma exLR profile in PDAC and to report an exLR signature for the detection of pancreatic cancer. This signature may improve the prognosis of patients who would have otherwise missed the curative treatment window.
Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells ...drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to 'drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.
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