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The development and malignancy of cancer cells are closely related to the changes of the epigenome. In this work, a mitochondria-targeted rhenium(I) complex (DFX-Re3), integrating the clinical iron chelating agent deferasirox (DFX), has been designed. By relocating iron to the mitochondria and changing the key metabolic species related to epigenetic modifications, DFX-Re3 can elevate the methylation levels of histone, DNA, and RNA. As a consequence, DFX-Re3 affects the events related to apoptosis, RNA polymerases, and T-cell receptor signaling pathways. Finally, it is shown that DFX-Re3 induces immunogenic apoptotic cell death and exhibits potent antitumor activity in vivo. This study provides a new approach for the design of novel epigenetic drugs that can recode the cancer epigenome by intervening in mitochondrial metabolism and iron homeostasis.

This meta-analysis aims to determine whether autologous fat grafting (AFG) affects the risk of local-regional recurrence (LRR) in breast cancer patients. In pooled analyses of 11 eligible studies, AFG was not associated with increased LRR. Subgroup analyses showed that AFG did not increase the risk of LRR in patients undergoing breast-conserving surgery or mastectomy, in patients with in situ carcinomas or invasive carcinomas, or in patients undergoing postoperative radiotherapy.

Background Non‐shared environment (NSE) effects account for around one‐third of the etiology of autism spectrum disorder (ASD). However, the knowledge of mechanisms and phenotypic profiles associated with NSE in ASD is scarce. Methods A systematic search was conducted using Embase, MEDLINE, and PsycINFO for studies published in English between 1990 and August 2020 using co‐twin control design to compare behavioral and biological phenotypes among monozygotic (MZ) twin pairs concordant/discordant for ASD, clinical autism symptoms, or autistic traits. Risk of bias was assessed through a modified Newcastle–Ottawa Scale. Results Twenty six articles were included. Differential DNA methylation and gene expression were found among ASD discordant twins; however, genetic results were inconsistent. Neurological disorders and early medical events were associated with ASD and autistic traits, while no within pair differences were found for minor physical anomalies or head circumference. Structural and functional brain imaging studies and research on social and other cognitive/behavioral functions were inconclusive. Risk of bias assessment found that all studies used the same exposure (or outcome) measures to collect data for participants and most used either secure health‐related records or structured interviews for ascertainment of exposure; however, only a handful of studies representative of the population from which they were drawn. Formal assessment of risk of publication bias (i.e., funnel plot) was not possible. Conclusions Our results suggest that NSE in ASD could be associated with heterogeneous postzygotic genetic mechanisms and manifest as a range of biological and behavioral phenotypes. Extant findings were limited by relatively few studies, small sample sizes, and methodological diversity. More research is needed on co‐occurring biological and behavioral phenotypes using a consistent format for designing, analyzing, and reporting MZ ASD discordant twin studies in order to further examine the role of NSE in the etiology of ASD.

Fluoride (sodium fluoride) is thought to be essential in the development of tooth, and research shows that fluoride can modulate the differentiation of dental stem cells. However, the effects of fluoride on the committed differentiation of stem cells from apical papilla (SCAPs) and the underlying mechanisms remain unclear. Here, SCAPs were isolated from healthy extracted human third molars with immature roots and then were cultured with NaF conditioned media. Cell Counting Kit-8, EdU staining, and flow cytometry were performed to detected the proliferation activity. Alkaline phosphatase (ALP) activity, Alizarin Red staining, Western blot assay, and real-time reverse-transcription polymerase chain reaction were applied to assess the osteo/odontogenic differentiation NaF-treated SCAPs. Western blot assay and transmission electron microscope were used to evaluate the autophagy involved in the differentiation of SCAPs. ALP activity, ALP protein, and messenger RNA (mRNA) expression showed that 0.5 mM was the optimal concentration for the induction of SCAPs by NaF. 0.5 mM NaF-treated SCAPs induced more mineralized nodules as compared with untreated cells. Moreover, the osteo/odontogenic markers (RUNX2, OSX, DSP, and OCN) in mRNA levels were upregulated while the protein levels of these markers increased considerably in 0.5 mM NaF-treated SCAPs. Furthermore, the autophagy-related proteins (LC3, ATG5, and Beclin1) increased in NaF-treated SCAPs, and the osteo/odontogenic makers significantly decreased while silencing ATG5 to block autophagy. In all, sodium fluoride can regulate the osteo/odontogenic differentiation of SCAPs by modulating autophagy.

Background Nausea and vomiting are the most common adverse reactions to chemotherapy. Aim To discuss the relationship between Helicobacter pylori and chemotherapy-induced nausea and vomiting (CINV). Methods A total of 112 patients with malignant tumours of the gastrointestinal tract was selected. Based on the 14C-urea breath test results, the patients were divided into H. pylori-positive (n = 59) and H. pylori-negative (n = 53) groups. Both groups received prophylactic antiemetic treatment during chemotherapy. The incidence of nausea and vomiting and their effects on the patients’ life functions was recorded using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemetic Tool (MAT) and the Functional Living Index Emesis (FLIE) from 0–120 h after chemotherapy. Records of the H. pylori-positive and H. pylori-negative groups were compared. Results The rates of nausea and vomiting remission were higher in the H. pylori -negative group than in the H. pylori -positive group. The proportions of no effect in daily life (NIDL) patients in the nausea and vomiting section were 73.4 and 75.5% in the H. pylori -negative group respectively. There was a higher proportion of NIDL patients in the H. pylori -negative group than in the H. pylori -positive group (P < 0.001, P = 0.046). A multivariate unconditional logistic regression analysis was performed, and the results showed that H. pylori infection was a factor affecting the nausea scores on the FLIE (odds ratio = 0.757, 95% confidence interval 0.597–0.960, P = 0.021). Conclusion H. pylori infection in patients with cancer may be a factor that increases CINV.

Immune thrombocytopenia (ITP) is an autoimmune disorder in which its immune system destroys platelets and leads to haemorrhage symptom. Recent studies have found that regulatory T cells (Tregs) in peripheral blood, bone marrow, and spleen were reduced in ITP patients and recovered after effective ITP therapy. Low-dose Interleukin-2 (IL-2) has been reported recently to increase Tregs and used to treat autoimmune disease including graft-versus-host disease (GVHD) after organ transplantation and HCV-related autoimmune vasculitis. However, it is unknown whether IL-2 is able to treat ITP. We have used low-dose IL-2 (1.0 million IU/day) on 5 consecutive days per week for 4 weeks in a 36-year-old patient with ITP. The result has shown that low-dose IL-2 induces expansion of Tregs significantly and increase platelet count was gradually from 36 × 109 /L to maximum 85 × 109 /L. No side effects of IL-2 have been found. This result suggested that low-dose of IL-2 may have therapeutic potential for ITP. © 2016 International Clinical Cytometry Society.

Exosomes can mediate intercellular communication by conveying various bioactive molecules. Plentiful evidence suggests that exosomes are involved in many liver diseases including hepatitis C virus infection, hepatitis B virus infection, hepatocellular carcinoma, liver fibrosis, cirrhosis, non-alcoholic fatty liver disease, and alcoholic liver disease. Moreover, exosomes are present in nearly all human body fluids. Therefore, exosomal miRNA or proteins have the potential to be novel biomarkers of liver diseases. In the treatment of liver diseases, exosomes could participate in adaptive immune response and mesenchymal stem cell-based therapy. Exosomes can also be used as vehicles for genetic materials and drug delivery.

We present a pilot study that aims to examine the possibility to easily and noninvasively detect and discriminate females with ovarian cancer (OC) from females that have no tumor(s) and from females that have benign genital tract neoplasia, using exhaled breath samples. The study is based on clinical samples and data from 182 females, as follows: 48 females with OC, 48 tumor-free controls and 86 females with benign gynecological neoplasia. Analysis of the breath samples with gas chromatography linked with mass spectrometry shows that decanal, nonanal, styrene, 2-butanone and hexadecane could serve as potential volatile markers for OC. Analysis of the same samples with tailor-made nanoarrays shows good discrimination between females with OC and females that have either no tumor or benign genital tract neoplasia (71% for accuracy, sensitivity and specificity). Conversely, the nanoarray output shows excellent discrimination between the OC patients and the tumor-free controls (79% sensitivity, 100% specificity and 89% accuracy). These results suggest that the nanoarray approach might be useful to avoid unnecessary complicated or expensive tests for tumor-free females in case of a negative result. In the case of positive result, the test will indicate with high probability the presence of OC.

The experiments were designed to evaluate the biocompatibility of a plastically compressed collagen scaffold (PCCS). The ultrastructure of the PCCS was observed via scanning electron microscopy. Twenty New Zealand white rabbits were randomly divided into experimental and control groups that received corneal pocket transplantation with PCCS and an amniotic membrane, respectively. And the contralateral eye of the implanted rabbit served as the normal group. On the 1st, 7th, 14th, 21st, 30th, 60th, 90th, and 120th postoperative day, the eyes were observed via a slit lamp. On the 120th postoperative day, the rabbit eyes were enucleated to examine the tissue compatibility of the implanted stroma. The PCCS was white and translucent. The scanning electron microscopy results showed that fibers within the PCCS were densely packed and evenly arranged. No edema, inflammation, or neovascularization was observed on ocular surface under a slit lamp and few lymphocytes were observed in the stroma of rabbit cornea after histological study. In conclusion, the PCCS has extremely high biocompatibility and is a promising corneal scaffold for an artificial cornea.

For a system of N electrons in an external scalar potential v(r) and external vector potential A(r), we prove that the wave function ψ is a functional of the gauge invariant ground state density ρ(r) and ground state physical current density j(r), and a gauge function α(R) (with R = r1,…,rN):ψ=ψ [ρ,j,α]. It is the presence of the gauge function α(R) that ensures the wave function functional is gauge variant. We prove this via a unitary transformation and by a proof of the bijectivity between the potentials {v(r),A(r)} and the ground state properties {ρ(r),j(r)}. Thus, the natural basic variables for the system are the gauge invariant ρ(r) and j(r). Because each choice of gauge function corresponds to the same physical system, the choice of α(R) = 0 is equally valid. As such, we construct a {ρ(r),j(r)} functional theory with the corresponding Euler equations for the density ρ(r) and physical current density j(r) , together with the constraints of charge conservation and continuity of the current. With the assumption of existence of a system of noninteracting fermions with the same ρ(r) and j(r) as that of the electrons, we provide the equations describing this model system, the definitions being within the framework of Kohn–Sham theory in terms of energy functionals of {ρ(r),j(r)} and their functional derivatives. A special case of the {ρ(r),j(r)} functional theory is the magnetic-field density-functional theory of Grayce and Harris. We discuss and contrast our work with the paramagnetic current- and density-functional theory of Vignale and Rasolt in which the variables are the gauge invariant ground state density ρ(r), and vorticity ν(r) = ∇× (jp(r)/ρ(r)) , where jp(r) is the paramagnetic current density. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

A new cardenolide and two new pregnane glycosides, periplogenin 3-[O-β-glucopyranosyl-(14)-β-sarmentopyranoside] (1), (3β,20S)-pregn-5-ene-3,17,20-triol 20-[O-β-glucopyranosyl-(16)-O-glucopyranosyl-(14)-β-canaropyranoside] (2), and (3β,14β,17α)-3,14,17-trihydroxy-21-methoxypregn-5-en-20-one 3-[O-β-oleandropyranosyl-(14)-O-β-cymaropyranosyl-(14)-β-cymaropyranoside] (3), were isolated from the root barks of Periploca sepiumBge, together with seven related known compounds, periplogenin, xysmalogenin, (3β,20S)-pregn-5-ene-3,17,20-triol, (3β,14β,17α)-3,14,17-trihydroxy-21-methoxypregn-5-en-20-one, (3β,20S)-pregn-5-ene-3,20-diol 3-β-glucopyranoside 20-β-glucopyranoside, (3β,20S)-pregn-5-ene-3,20-diol 3-[O-2-O-acetyl-β-digitalopyranosyl-(14)-β-cymaropyranoside] 20-[O-β-glucopyranosyl-(16)-O-β-glucopyranosyl-(12)-β-digitalopyranoside], and (3β,20S)- pregn-5-ene-3,20-diol 20-[O-β-glucopyranosyl-(16)-β-glucopyranoside]. Their structures were elucidated on the basis of spectroscopic analyses.

The fundamental theorem of time-independent/time-dependent density functional theory due to Hohenberg–Kohn (HK)/Runge–Gross (RG) proves the bijectivity between the density ρ(r)/ρ(rt) and the Hamiltonian /(t) to within a constant C/function C(t), and wave function Ψ/Ψ (t). The theorems are each proved for scalar external potential energy operators. By a unitary or equivalently a gauge transformation that preserves the density, we generalize the realm of validity of each theorem to Hamiltonians, which additionally include the momentum operator and a curl-free vector potential energy operator defined in terms of a gauge function α (R)/α (Rt). The original HK/RG theorems then each constitute a special case of this generalization. Thereby, a fourfold hierarchy of such theorems is established. As a consequence of the generalization, the wave function Ψ/Ψ (t) is shown to be a functional of both the density ρ(r)/ρ(rt), which is a gauge-invariant property, and a gauge function α(R)/α(Rt). The functional dependence on the gauge function ensures that as required by quantum mechanics, the wave function written as a functional is gauge variant. The hierarchy and the dependence of the wave function functional on the gauge function thus enhance the significance of the phase factor in density functional theory in a manner similar to that of quantum mechanics. Various additional perspectives on the theorem are arrived at. These understandings also address past critiques of time-dependent theory. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008

For approximate wave functions, we prove the theorem that there is a one-to-one correspondence between the constraints of normalization and of the Fermi–Coulomb and Coulomb hole charge sum rules at each electron position. This correspondence is surprising in light of the fact that normalization depends on the probability of finding an electron at some position. In contrast, the Fermi–Coulomb hole sum rule depends on the probability of two electrons staying apart because of correlations due to the Pauli exclusion principle and Coulomb repulsion, while the Coulomb hole sum rule depends on Coulomb repulsion. We demonstrate the theorem for the ground state of the He atom by the use of two different approximate wave functions that are functionals rather than functions. The first of these wave function functionals is constructed to satisfy the constraint of normalization, and the second that of the Coulomb hole sum rule for each electron position. Each is then shown to satisfy the other corresponding sum rule. The significance of the theorem for the construction of approximate “exchange-correlation” and “correlation” energy functionals of density functional theory is also discussed. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

In our Reply, we first explain why the proof of Vignale and Rasolt that the basic variables are the density and paramagnetic current density is in error. We then refute the comments by Vignale et al with regard to our work. © 2012 Wiley Periodicals, Inc.