Both platinum-based doublet chemotherapy （PBC） and epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） prolong the survival of patients with advanced non-small cell lung cancer ...（NSCLC）. In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival （OS）. Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria： in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase Ill clinical trials--involving 11,456 adult patients in 32 arms--were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian （predominantly Caucasian） populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs （r = 0.797, P 〈 0.001）. The correlation was obvious in the trials in Asian populations （r= 0.936, P 〈 0.001） but was not statistically significant in the trials in predominantly Caucasian populations （r = 0.116, P = 0.588）. These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalJtJes available for therapy.
Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease（KBD） and in an established T-2 toxin-and selenium（Se） ...deficiency-induced rat model. Methods Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and m RNA levels were determined by real-time reverse transcription polymerase chain reaction. Results Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and m RNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. Conclusion T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.
Background
Dysregulation of the type 1 interferon (IFN)‐related signalling pathway predisposes one to autoimmune diseases. Possible associations of single‐nucleotide polymorphisms (SNPs) of secreted ...phosphoprotein 1 (SPP1) and B lymphocyte kinase (BLK) of the type 1 IFN‐related signalling pathway with autoimmune thyroid disease (AITD) in an ethnic Chinese (ie Taiwanese) population were tested.
Methods
Totally, 83 Hashimoto's thyroiditis (HT) patients, 319 Graves’ disease (GD) patients and 369 controls were enrolled. Genotypes of the two SNPs (rs1126772 and rs1126616) of SPP1 and two SNPs (rs13277113 and rs2736340) of BLK were determined.
Results
Our results showed reduced percentages of the G allele of rs13277113 of BLK in GD (P = 0.037, odds ratio OR = 0.78, 95% confidence interval CI = 0.62‐0.99) and HT (P = 0.002, OR = 0.54, 95% CI = 0.36‐0.81), compared to the controls. At the same time, lower frequencies of the C allele of rs2736340 of BLK in GD (P = 0.025, OR = 0.76, 95% CI = 0.60‐0.97) and HT (P = 0.003, OR = 0.53, 95% CI = 0.35‐0.81) than the controls were also observed. There were significantly higher AT haplotype frequencies of rs1327713 and rs2736340 in GD and HT patients than in the controls (P = 0.025, OR = 1.31, 95% CI = 1.03‐1.67, and P = 0.003, OR = 1.89, 95% CI = 1.24‐2.87, respectively). Moreover, the anti‐microsomal antibody titre was associated with rs2736340.
Conclusions
Genetic variants of rs13277113 and rs2736340 of BLK were associated with susceptibility to GD, HT and AITD in an ethnic Chinese population. Our results suggest the BLK may participate in the pathogenesis of GD, HT and AITD.
Oral squamous cell carcinoma is an increasingly prevalent cancer type characterized by high incidence and mortality rates. Its early detection is challenging, primarily because of the absence of ...early molecular markers. Cuproptosis is a novel regulatory mechanism of cell death with implications in various cancers. In this study, we aimed to study cuproptosis-related genes in oral squamous cell carcinoma to identify their prognostic value.
By analyzing genomic, bulk RNA-seq, and single-cell RNA-seq data, we investigated 13 cuproptosis-related genes in The Cancer Genome Atlas-Oral Squamous Cell Carcinoma dataset and Gene Expression Omnibus repository (GSE172577).
ATP7A, ATP7B, and DLST were the most frequently mutated genes, with nine of our studied genes associated with overall survival. Single-cell analysis was conducted to identify cuproptosis-related tumor cells in oral squamous cell carcinoma, which revealed two distinct patterns based on the expression of cuproptosis-related genes. These patterns exhibit differences in genetic alterations and tumor immune microenvironment. Finally, we developed a cuproptosis index using a random forest algorithm based on cuproptosis pattern-related genes in which higher levels were linked to poorer prognosis.
Our findings provide valuable insights into the mechanisms underlying oral squamous cell carcinoma-associated cuproptosis.
Stomatal closure is regulated by plant hormones and some small molecules to reduce water loss under stress conditions. Both abscisic acid (ABA) and polyamines alone induce stomatal closure; however, ...whether the physiological functions of ABA and polyamines are synergistic or antagonistic with respect to inducing stomatal closure is still unknown. Here, stomatal movement in response to ABA and/or polyamines was tested in Vicia faba and Arabidopsis thaliana, and the change in the signaling components under stomatal closure was analyzed. We found that both polyamines and ABA could induce stomatal closure through similar signaling components, including the synthesis of hydrogen peroxide (H2O2) and nitric oxide (NO) and the accumulation of Ca2+. However, polyamines partially inhibited ABA‐induced stomatal closure both in epidermal peels and in planta by activating antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), to eliminate the ABA‐induced increase in H2O2. These results strongly indicate that polyamines inhibit abscisic acid‐induced stomatal closure, suggesting that polyamines could be used as potential plant growth regulators to increase photosynthesis under mild drought stress.
The B-lymphocyte-activating factor (BAFF) is associated with B-cell functions, and gene polymorphisms of the BAFF have been linked to autoimmune diseases (AIDs). In this study, we explored possible ...associations of two BAFF single-nucleotide polymorphisms (SNPs), rs1041569 and rs2893321, with autoimmune thyroid diseases (AITDs) in an ethnic Chinese population.
In total, 319 Graves' disease (GD), 83 Hashimoto's thyroiditis (HT) patients, and 369 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were used to genotype rs2893321 and rs1041569.
There was a significant difference in frequencies of the G allele and AG+GG genotype of rs2893321 between the GD and control groups (p = 0.013, odds ratio (OR) = 0.76, and p = 0.017, OR = 0.68, respectively) and between the AITD and control groups (p = 0.009, OR = 0.76, and, p = 0.014, OR = 0.69, respectively). The AA genotype of rs2893321 was associated with low titers of the thyroid-stimulating hormone receptor antibody (TSHRAb) (p = 0.015) in males but not in females. The AA genotype of rs2893321 was associated with the presence of two different types of thyroid autoantibody (TAb) (TSHRAb and Hashimoto's autoantibody (anti-thyroglobulin or anti-microsomal antibody)) in females and with that of one type in males.
rs2893321 may be a susceptible genetic variant for the development of GD and AITDs. Associations of rs2893321 with susceptibility to GD and AITDs and the correlation between rs2893321 and TAb exhibit a dimorphic pattern. Additional studies with larger sample sizes are required to confirm our findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hexagonal boron nitride (hBN) has recently been demonstrated to contain optically polarized and detected electron spins that can be utilized for implementing qubits and quantum sensors in ...nanolayered-devices. Understanding the coherent dynamics ofmicrowave driven spins in hBN is of crucial importance for advancing these emerging new technologies. Here, we demonstrate and study the Rabi oscillation and related phenomena of a negatively charged boron vacancy (V-B(-)) spin ensemble in hBN. We report on different dynamics of the V-B(-) spins at weak and strong magnetic fields. In the former case the defect behaves like a single electron spin system, while in the latter case it behaves like a multi-spin system exhibiting multiple-frequency dynamical oscillation as beat in the Ramsey fringes. We also carry out theoretical simulations for the spin dynamics of V-B(-) and reveal that the nuclear spins can be driven via the strong electron nuclear coupling existing in V-B(-) center, which can be modulated by the magnetic field and microwave field.
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•A two-dimensional semiconductor monolayer PdI2 has been predicted from its van der Walls bulk material.•PdI2 monolayer exhibits an extraordinary in-plane negative Poisson ratio ...(-0.183).•Ultralow lattice thermal conductivity (0.23 ∼ 0.34 Wm-1 K-1) have been revealed in monolayer PdI2 at room temperature.•The V-shaped crystal structure makes PdI2 monolayer an excellent platform for alkali ions migration (0.08 eV to 0.152 eV).
Using first-principles calculations, we predicted a multifunctional two-dimensional (2D) semiconductor PdI2 from its van der Walls layered bulk. Monolayer or multilayer PdI2 obtained by mechanical exfoliation exhibit high stability as freestanding 2D materials. Originating from its special corner-shared quasi-plane crystal structure, an amazing in-plane negative Poisson's ratio in monolayer PdI2 has been confirmed. The layer dependent electronic and thermal properties have also been discussed in detail. Encouragingly, it has been found that strong phonon scattering which is induced by low symmetry will further reduce the lattice thermal conductivity in monolayer PdI2 at room temperature. Besides, the monolayer PdI2 is seen as an excellent platform for alkali ions migration with ultralow diffusion barriers, benefiting from its distinctive V-shaped crystal structure. Considering these interesting findings, we believe the 2D PdI2 will be a promising candidate for future's low dimensional electron devices.
It has been suggested that a trade‐off between hydraulic efficiency and safety is related to drought adaptation across species. However, whether leaf hydraulic efficiency is sacrificed for safety ...during woody resprout regrowth after crown removal is not well understood. We measured leaf water potential (ψleaf) at predawn (ψpd) and midday (ψmid), leaf maximum hydraulic conductance (Kleaf‐max), ψleaf at induction 50% loss of Kleaf‐max (Kleaf P50), leaf area‐specific whole‐plant hydraulic conductance (LSC), leaf vein structure and turgor loss point (πtlp) in 1‐ to 13‐year‐old resprouts of the aridland shrub (Caragana korshinskii). ψpd was similar, ψmid and Kleaf P50 became more negative, and Kleaf–max decreased in resprouts with the increasing age; thus, leaf hydraulic efficiency clearly traded off against safety. The difference between ψmid and Kleaf P50, leaf hydraulic safety margin, increased gradually with increasing resprout age. More negative ψmid and Kleaf P50 were closely related to decreasing LSC and more negative πtlp, respectively, and the decreasing Kleaf‐max arose from the lower minor vein density and the narrower midrib xylem vessels. Our results showed that a clear trade‐off between leaf hydraulic efficiency and safety helps C. korshinskii resprouts adapt to increasing water stress as they approach final size.
A trade‐off between leaf hydraulic efficiency and safety is proposed to be related to drought adaptation, but it is still under debate. Here, leaf hydraulic efficiency clearly traded off against safety in resprouts of Caragana korshinskii, thus helping resprouts adapt to increasing water stress.
Insulin-like growth factor-1 (IGF-1) is a potent neuroprotective polypeptide that exerts neuroprotective effects via the IGF-1 receptor (IGF-1R). Our previous study reported that G protein-coupled ...estrogen receptor (GPER) was involved in the anti-apoptotic effect of IGF-1. The present study was designed to investigate the anti-inflammatory effect of IGF-1 in association with astrocyte activation and the molecular details of the interaction between IGF-1R and GPER. We showed that IGF-1 could improve 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor deficits and attenuate the upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) both in vivo and in vitro. The IGF-1R antagonist JB-1 and the GPER antagonist G15 could antagonize the anti-inflammatory effect of IGF-1. Silencing GPER abrogated the inhibitory effect of IGF-1 on 1-methyl-4-phenylpyridinium (MPP+)-induced upregulation of COX-2 and iNOS in primary astrocytes. Moreover, the MPP + -induced inflammatory response was related to the activation of mitogen-activated protein kinases (MAPKs) and NF-κB signaling pathways. The inhibitory effects of IGF-1 on the phosphorylation of p38, JNK and IκB could be blocked by JB-1. G15 antagonized the inhibitory effects of IGF-1 on p-JNK and p-IκB, but not p-p38. Furthermore, IGF-1 treatment alone increased the expression of GPER, which was blocked by JB-1, the phosphatidylinositol 3-kinase (PI3–K) antagonist LY294002 and the MEK antagonist PD98059 in primary astrocytes. Overall, we show for the first time that GPER may contribute to the anti-inflammatory effect of IGF-1 against MPTP/MPP + -induced astrocyte activation. IGF-1 could regulate the expression of GPER via the IGF-1R/PI3-K/MAPK signaling pathway in primary astrocytes.
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•IGF-1 protects against MPTP/MPP + -induced astrocyte activation.•GPER contributes to the anti-inflammatory effects of IGF-1.•IGF-1 can regulate GPER protein expression through PI3K/MAPK signaling pathways.
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