Explore the vast range of titles available.

Grace, sixteen, fears that she'll succumb to the schizophrenia that took her mother away, while she and her father work for a genetics lab rushing to find a cure.

Lactate is an end product of glycolysis. As a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule. We briefly summarize emerging concepts regarding lactate metabolism, such as the lactate shuttle, lactate homeostasis, and lactate-microenvironment interaction. Accumulating evidence indicates that lactate-mediated reprogramming of immune cells and enhancement of cellular plasticity contribute to establishing disease-specific immunity status. However, the mechanisms by which changes in lactate states influence the establishment of diverse functional adaptive states are largely uncharacterized. Posttranslational histone modifications create a code that functions as a key sensor of metabolism and are responsible for transducing metabolic changes into stable gene expression patterns. In this review, we describe the recent advances in a novel lactate-induced histone modification, histone lysine lactylation. These observations support the idea that epigenetic reprogramming-linked lactate input is related to disease state outputs, such as cancer progression and drug resistance.

As her senior year in high school approaches, Mina yearns to find her own path in life but working at the family business, taking care of her little sister, and dealing with her mother's impossible expectations are as stifling as the southern California heat, until she falls in love with a man who offers a way out.

Overproduction of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.

This study identifies opposite changes in two main subtypes of inhibitory neurons in the mouse motor cortex during motor learning. With learning, the number of synapses made by somatostatin-expressing inhibitory neurons (SOM-IN) onto the distal dendritic branches of pyramidal neurons decreased, whereas the number of perisomatic contacts made by parvalbumin-positive cells increased. The authors also found that optogenetic disruption of SOM-IN activity resulted in impairment of learning-related dendritic spine reorganization and motor learning. Motor skill learning induces long-lasting reorganization of dendritic spines, principal sites of excitatory synapses, in the motor cortex. However, mechanisms that regulate these excitatory synaptic changes remain poorly understood. Here, using in vivo two-photon imaging in awake mice, we found that learning-induced spine reorganization of layer (L) 2/3 excitatory neurons occurs in the distal branches of their apical dendrites in L1 but not in the perisomatic dendrites. This compartment-specific spine reorganization coincided with subtype-specific plasticity of local inhibitory circuits. Somatostatin-expressing inhibitory neurons (SOM-INs), which mainly inhibit distal dendrites of excitatory neurons, showed a decrease in axonal boutons immediately after the training began, whereas parvalbumin-expressing inhibitory neurons (PV-INs), which mainly inhibit perisomatic regions of excitatory neurons, exhibited a gradual increase in axonal boutons during training. Optogenetic enhancement and suppression of SOM-IN activity during training destabilized and hyperstabilized spines, respectively, and both manipulations impaired the learning of stereotyped movements. Our results identify SOM inhibition of distal dendrites as a key regulator of learning-related changes in excitatory synapses and the acquisition of motor skills.

Transition metal-catalyzed C–H bond functionalization is an important method in organic synthesis, but the development of methods that are lower cost and have a less environmental impact is desirable. Here, a Cu-catalyzed asymmetric C(sp 2 )–H arylation is reported. With diaryliodonium salts as arylating reagents, a range of ortho -arylated P - chiral phosphonic diamides were obtained in moderate to excellent yields with high enantioselectivities (up to 92% ee). Meanwhile, enantioselective C-3 arylation of diarylphosphine oxide indoles was also realized under similar conditions to construct axial chirality. Although transition metal-catalyzed C–H bond functionalization is a widely used method in organic synthesis, many methods rely on metals of low abundance. Here, the authors report a copper-catalyzed, asymmetric C–H arylation using diaryliodonium salts.

Background Direct and indirect effects of radiofrequency ablation (RFA) on tumor microenvironment of the liver tumor have been noted, which was reported to be related to a variety of tyrosine protein kinase or cytokinetic pathway, but have not been thoroughly investigated and conclusive. Purpose To elucidate direct and indirect effects of RFA on tumor microenvironment in the liver tumor model, and to explore the role of the specific inhibitor in tumor growth by targeting the key pathway of RFA. Materials and methods One hundred and ten mice with H22 liver tumor were used in animal experiments. Eighty-four mice were randomized into three groups: control, direct RFA and indirect RFA (a block slide was inside the middle of the tumor). The growth rate of the residual tumor after RFA was calculated ( n  = 8 each group) and the pathologic changes at different time points (6 h, 24 h, 72 h and 7d after RFA) were evaluated ( n  = 5 in each subgroup). After semi-quantitative analysis of the pathological staining, the most significant marker after RFA was selected. Then, the specific inhibitor (PHA) was applied with RFA and the tumor growth and pathological changes were evaluated and compared with RFA alone. The Kruskal-Wallis test was used for evaluating the significance of different treatments in the pathological positive rate of specific markers in tumor. The two-way analysis of variance was used to determine the significance of treatment in tumor growth or body weight. Results The growth rate of the residual tumor in the direct RFA group was faster than the indirect RFA group ( P  = 0.026). The pathological analysis showed the expression of HSP70 (73 ± 13% vs 27 ± 9% at 24 h, P  < 0.001), SMA (70 ± 18% vs 18 ± 7% at 6 h, P  < 0.001) and Ki-67 (51 ± 11% vs 33 ± 14% at 7d, P  < 0.001) in the direct RFA group was higher than those in the indirect RFA group after RFA. On the other hand, the expression of c-Met (38 ± 11% vs 28 ± 9% at 24 h, P  = 0.01), IL-6 (41 ± 10% vs 25 ± 9% at 24 h, P  < 0.001) and HIF-α (48 ± 10% vs 28 ± 8% at 24 h, P  < 0.001) in the indirect RFA group was higher than those in the direct RFA group. And the expression of c-Met increased mostly in both direct and indirect RFA group compared to the baseline (53 and 65% at 72 h). Then the specific inhibitor of c-Met-PHA was applied with RFA. The growth rate of the tumor was significantly slower in the RFA + PHA group than the RFA alone group (1112.9 ± 465.6 mm 3 vs 2162.7 ± 911.1 mm 3 at day 16, P  = 0.02). Conclusion Direct and indirect effects of RFA on tumor microenvironment changed at different time points and resulted in increased residual tumor growth in the animal model. It can be potentially neutralized with specific inhibitor of related pathways, such as tyrosine-protein kinase c-Met.

Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid‐gestational age—the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case–control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis. Synopsis Mass spectrometry‐based proteomics for plasma proteome profiling were performed on early gestational pregnant women with or without congenital heart disease (CHD) offspring. In‐depth analysis revealed a potential pathogenic mechanism and identified a set of biomarkers in early gestational plasma predicting fetal CHD. A total of 104 early gestational pregnant women with CHD offspring and 103 controls with healthy offspring were included. A total of 264 proteins were found significantly upregulated and 358 proteins downregulated in the plasma of early gestational pregnant women with CHD offspring. Dyslipidemia and CD4 + might be involved in the occurrence of CHD. Nine CHD‐related biomarkers had been identified. Graphical Abstract Mass spectrometry‐based proteomics for plasma proteome profiling was performed on early gestational pregnant women with or without congenital heart disease (CHD) offspring. In‐depth analysis revealed a potential pathogenic mechanism and identified a set of biomarkers in early gestational plasma predicting fetal CHD.

Cervical cancer is a devastating cancer and is currently ranked as the fourth most prevalent type of cancer in the world. The lack of efficacious chemotherapy forms a bottleneck in the treatment of cervical cancer. This study was therefore undertaken to evaluate the anticancer effects of camelliol C against human cervical cancer cells. Normal cell line (NCEC) and cervical cancer cell lines (Csdki, HeLa, C33A, and siHa) were used in this study. Cell viability was determined by MTT assay, and apoptosis was detected by DAPI and annexin V/PI staining. Cell cycle analysis, ROS, and MMP levels were examined by flow cytometry. Cell migration and invasion was monitored by transwell assays. The results showed that camelliol C inhibits the proliferation of all the human cervical cancer cell lines with IC ranging from 10 to 20 µM. However, comparatively low antiproliferative effects were observed on the normal cells. Investigation of the underlying mechanisms showed that camelliol C induces apoptosis in HeLa cancer cells. Camelliol C-triggered apoptosis was also linked with cleavage of caspase-3 and -9, and PARP. Additionally, the Bax protein levels were increased and those of Bcl-2 were decreased. Transwell assays showed that camelliol C suppresses the migration and invasion of the HeLa cervical cancer cells. Additionally, camelliol C also blocked the PI3K/AT signalling cascade dose dependently. Camelliol C may prove beneficial in the treatment of cervical cancer.

Thermal management in devices directly affects their performance, but it is difficult to apply conventional cooling methods such as the use of cooling liquids or fans to micro devices owing to the small size of micro devices. In this study, we attempted to solve this problem by employing a heat sink fabricated using copper with porous structures consisting of single-layer graphene on the surface and graphene oxide inside the pores. The porous copper/single-layer graphene/graphene oxide composite (p-Cu/G/rGO) had a porosity of approximately 35%, and the measured pore size was approximately 10 to 100 µm. The internal GO was reduced at a temperature of 1000 °C. On observing the heat distribution in the structure using a thermal imaging camera, we could observe that the p-Cu/G/rGO was conducting heat faster than the p-Cu, which was consistent with the simulation. Furthermore, the thermal resistance of p-Cu/G/rGO was lower than those of the p-Cu and pure Cu. When the p-Cu/G/rGO was fabricated into a heat sink to mount the light emitting diode (LED) chip, the measured temperature of the LED was 31.04 °C, which was less than the temperature of the pure Cu of 40.8 °C. After a week of being subjected to high power (1000 mA), the light intensity of p-Cu/G/rGO decreased to 95.24%. However, the pure Cu decreased significantly to 66.04%. The results of this study are expected to be applied to micro devices for their effective thermal management.