The deterministic rotation of magnetization by electric fields is a challenging issue for future low‐power spintronics. In a Co/0.7Pb(Mg1/3Nb2/3)O3−0.3PbTiO3 multiferroic heterostructure, ...piezostrain‐mediated, macroscopically maneuverable, and non‐volatile magnetization reversal without an applied magnetic field is demonstrated. This, combined with the presented phase‐field simulations, is of practical relevance for designing prototype devices.
Breast cancer (BC) is the most common malignancy in women worldwide, and it is a molecularly diverse disease. Heterogeneity can be observed in a wide range of cell types with varying morphologies and ...behaviors. Molecular classifications are broadly used in clinical diagnosis, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and breast cancer gene (BRCA) mutations, as indicators of tumor heterogeneity. Treatment strategies differ according to the molecular subtype. Besides the traditional treatments, such as hormone (endocrine) therapy, radiotherapy, and chemotherapy, innovative approaches have accelerated BC treatments, which contain targeted therapies and immunotherapy. Among them, monoclonal antibodies, small-molecule inhibitors and antibody–drug conjugates, and targeted delivery systems are promising armamentarium for breast cancer, while checkpoint inhibitors, CAR T cell therapy, cancer vaccines, and tumor-microenvironment-targeted therapy provide a more comprehensive understanding of breast cancer and could assist in developing new therapeutic strategies.
Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory ...network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.
Background
Small cell lung cancer (SCLC) is one of the deadliest malignancies and accounts for nearly 15% of lung cancers. Previous study had revealed the genomic characterization of SCLC in Western ...patients. However, little is known about that in Chinese SCLC patients.
Methods
Formalin‐fixed paraffin‐embedded tumor tissues and matched blood samples from 122 Chinese SCLC patients were collected for next generation sequencing to detect 450 cancer‐related genes. All pathological diagnoses were confirmed by independent pathologists.
Results
The most frequently altered genes were TP53 (93.4%), RB1 (78.7%), LRP1B (18.9%), KMT2D (15.6%), FAT1 (11.5%), KMT2C (11.5%), SPTA1 (11.5%), STK24 (11.5%), FAM135B (10.7%), and NOTCH1 (10.7%). The gene fusion/rearrangement detection rate was 16.4%, and mostly occurred in chromosomes 7 and 17. The rate of co‐occurring mutations of TP53 and RB1 in these Chinese SCLC patients was 74.6%, and lower than the reported Western patients (90.9%, P = 0.007). The most common gene mutations (83.6%) were found in cell cycle signaling pathway in Chinese SCLC patients. Mutation of Wnt and Notch signaling pathways in the Chinese cohort were lower than Western cohort (P = 0.0013 and 0.0068). A significant association was found between high tumor mutation burden and mutations involved in FAT1, TP53, SPTA1, KEAP1, KMT2D, MAGI2, NOTCH2, NOTCH3, FLT1, KDM6A, and FAT4.
Conclusions
In this study, we characterized the genomic alterations profile of Chinese SCLC patients. Compared with westerners, the genetic alterations of Chinese SCLC patients presented different patterns. Our data might provide useful information in targeted therapy and drug development for Chinese SCLC patients.
In Chinese small cell lung cancer (SCLC) cohort, the 10 most frequently mutated genes were TP53 (93.4%), RB1 (78.7%), LRP1B (18.9%), KMT2D (15.6%), FAT1 (11.5%), KMT2C (11.5%), SPTA1 (11.5%), STK24 (11.5%), FAM135B (10.7%), and NOTCH1 (10.7%). Comparing with the previously reported data mainly in Western patients, the rate of co‐occurring mutations of TP53 and RB1 in Chinese patients was lower. In addition, mutations of Wnt and Notch signaling pathways were also lower than Western cohort. Our data indicated that Chinese patients with SCLC had unique characteristics in tumor‐related genomic alterations, which provided useful information in targeted therapy and drug development for Chinese SCLC patients.
Innate lymphoid cells (ILCs) have been identified as a heterogeneous population of lymphocytes that mirrors the cytokine and transcriptional profile of adaptive T cells. The dynamic balance between ...key transcription factors determines the heterogeneity, plasticity, and functions of ILC subsets. The transcription factor ThPOK is highly conserved in biological evolution and exerts pivotal functions in the differentiation of T cells. However, the function of ThPOK in ILC3s has not been identified. Here, we found that ThPOK regulated the homeostasis of ILC3s, as mice lacking ThPOK showed decreased NKp46
+
ILC3s and increased CCR6
-
NKp46
-
ILC3s. ThPOK-deficient mice were more sensitive to
S. typhimurium
infection due to the impaired IFN-γ secretion of NKp46
+
ILC3s. Furthermore, ThPOK participates in ILC3-mediated control of
C. rodentium
infection by negatively regulating IL-17A secretion. ThPOK preserves the identity of NKp46
+
ILC3s by repressing RORγt, which indirectly releases T-bet expression. On the molecular level, ThPOK directly binds to
Rorc
and
Il23r
to restrain their expression which further modulates IL-17A secretion. Collectively, our analysis revealed a critical role of ThPOK in the homeostasis and functions of ILC3 subsets.
We review colossal magnetoresistance in single phase manganites, as related to the field sensitive spin-charge interactions and phase separation; the rectifying property and negative/positive ...magnetoresistance in manganite/Nb：SrTio3 p-n junctions in relation to the special interface electronic structure; magnetoelectric coupling in manganite/ferroelectric structures that takes advantage of strain, carrier density, and magnetic field sensitivity; tunneling magnetoresistance in tunnel junctions with dielectric, ferroelectric, and organic semiconductor spacers using the fully spin polarized nature of manganites; and the effect of particle size on magnetic properties in manganite nanoparticles.
Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in ...the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated.
To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM.
We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure.
Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report a study on the interfacial antiferromagnetic coupling between ferrimagnetic TbIG/YIG thin films. TbIG/YIG bilayers are grown on YAG (110) substrates. The crystal structure and magnetic ...properties of the films are characterized. The temperature and directional dependences of the antiferromagnetic coupling effect are observed at low temperatures. This work enriches the magnetic research of ferrimagnetic oxide films with complex structures, providing new ideas for the design of antiferromagnetically coupled spintronics devices.
(1 −
x
)K
0.44
Na
0.52
Li
0.04
Nb
0.96
Sb
0.04
O
3
–
x
Bi
0.25
Na
0.25
Ba
0.5
ZrO
3
(1 −
x
)KNLNS-
x
BNBZ (0 ≤
x
≤ 0.05) lead-free piezoelectric ceramics were prepared by using the conventional ...solid-state reaction method. The relationships among the composition, phase structure, phase volume fraction, microstructure, dielectric, ferroelectric, and piezoelectric properties as well as the phase diagram are established. Rietveld refinements of X-ray diffraction patterns show that with increasing doping level the volume fractions of the orthorhombic and tetragonal phases evolve from 58.7 and 41.3% for
x
= 0 to 1.7 and 98.3% for
x
= 0.05, which has strong impacts on the piezoelectric coefficient
d
33
and Curie temperature
T
C
. Upon the doping of BNBZ an orthorhombic-tetragonal (
O
–
T
) phase boundary forms near room temperature, resulting in an optimum
d
33
~ 288 pC/N,
T
C
~ 305 °C, a converse piezoelectric coefficient
d
33
*
~ 391 pm/V, and a field-induced strain
S
~ 0.156% for the
x
= 0.035 ceramics. These results demonstrate that a balanced development of
d
33
and
T
C
can be realized by choosing suitable doping materials and content.
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