Tryptophan metabolic pathway plays a key role in the stress-induced emotional eating.

Chronic stress disrupts the emotional and energetic balance, which may lead to abnormal behaviors such as binge eating. This overeating behavior alleviating the negative emotions is called emotional eating, which may exacerbate emotional instability and lead to obesity. It is a complex and multifaceted process that has not yet been fully understood. In this study, we constructed an animal model of chronic mild stress (CMS)-induced emotional eating. The emotional eating mice were treated with tryptophan for 21 days to reveal the key role of tryptophan. Furthermore, serum-targeted metabolomics, immunohistochemical staining, qPCR and ELISA were performed. The results showed that CMS led to the binge eating behavior, accompanied by the disturbed intestinal tryptophan-derived serotonin (5-hydroxytryptamine; 5-HT) metabolic pathways. Then we found that tryptophan supplementation improved depression and anxiety-like behaviors as well as abnormal eating behaviors. Tryptophan supplementation improved the abnormal expression of appetite regulators (e.g., AgRP, OX1R, MC4R), and tryptophan supplementation also increased the tryptophan hydroxylase 2 (tph2) and 5-HT receptors in the hypothalamus of CMS mice, which indicates that the 5-HT metabolic pathway influences feeding behavior. In vitro experiments confirmed that 5-HT supplementation ameliorated corticosterone-induced aberrant expression of appetite regulators, such as AgRP and OX1R, in the hypothalamic cell line. In conclusion, our findings revealed that the tryptophan-derived 5-HT pathway plays an important role in emotional eating, especially in providing targeted therapy for stress-induced obesity.

LEPR/FOS/JUNB signaling pathway contributes to chronic restraint stress-induced tumor proliferation.

BACKGROUND & AIMS: Psychosocial stress has become an unavoidable part of life, which was reported to promote tumor development. Chronic stress significantly promotes the norepinephrine (NE) secretion and the expression of leptin receptor (LEPR), leading to tumor invasion, metastasis, and proliferation. However, the mechanism of chronic stress-induced tumor proliferation remains unclear. METHODS: To reveal the effect of chronic stress on tumor proliferation, subcutaneous tumor models combined with chronic restraint stress (CRS) were established. Combined with the transcript omics database of liver cancer patients, the target pathways were screened and further verified by in vitro experiments. RESULTS: The results showed that the CRS with subcutaneous tumor transplantation (CRS + tumor) group exhibited significantly larger tumor sizes than the subcutaneous tumor transplantation (tumor) group. Compared with the tumor group, CRS obviously increased the mRNA levels of LEPR, FOS, and JUNB of tumor tissues in the CRS + tumor group. Furthermore, the treatment with norepinephrine (NE) significantly elevated the survival rate of H22 cells and enhanced the expression of LEPR, FOS, and JUNB in vitro. Silencing LEPR significantly reduced the expression of FOS and JUNB, accompanied by a decrease in H22 cell viability. CONCLUSIONS: Our study demonstrated that CRS activates the LEPR-FOS-JUNB signaling pathway by NE, aggravating tumor development. These findings might provide a scientific foundation for investigating the underlying pathological mechanisms of tumors in response to chronic stress.

HIF1α/miR-146α/TRAF6/NF-κB axis modulates hepatic iron overload-induced inflammation.

Transfusional therapy is used to cure anemia but raises the risk of hepatic iron overload (IO), which triggers oxidative stress damage, inflammation, and failure even fibrosis. microRNAs play a vital role in developing hepatic diseases. This study presented the mechanism by which IO induce hepatic inflammation through microRNAs. In this study, microRNA expression profiling in the liver was observed after IO for 2 weeks, in which the target microRNA will be found. IO activating the miR-146α/TRAF6/NF-κB pathway was validated, and the molecular mechanism of the IO-induced decrease of miR-146α in the liver was studied in vivo and in vitro. The expression of TRAF6/NF-κB (p65)-dependent inflammatory factors increased, whereas the expression of miR-146α decreased during the IO-induced inflammatory response in the liver. The reduced expression of HNF4α caused by HIF1α and miR-34α may decrease the expression of miR-146α. Overexpression of miR-146α alleviated the hepatic inflammatory response caused by IO. Our findings indicate that miR-146α is a key factor in inducing hepatic IO inflammation, which will be another potential target to prevent IO-induced hepatic damage.

Deformation Characteristics of Three-Dimensional Spiral Soft Actuator Driven by Water Hydraulics for Underwater Manipulator.

The emergence of bionic soft robots has led to an increased demand for bionic soft actuating ends. In this study, a three-dimensional spiral water hydraulic soft actuator (3D-SWHSA), inspired by the winding action of an elephant's trunk, is proposed to provide a more targeted soft actuator catching method. The 3D-SWHSA is composed of multiple bending and twisting units (BATUs), which can produce winding deformation after being pressed. By using the principles of virtual work and integrating the Yeoh 3rd order model, a predictive model for winding was established to investigate the bending and twisting characteristics of BATUs with varying structural parameters through finite element simulation. Following the selection of an optimal set of structural parameters for the 3D-SWHSA, its bending and deformation capabilities were simulated using finite element analysis and subsequently validated experimentally. To validate its flexibility, adaptability, and biocompatibility, successful catching experiments were conducted in both air and underwater environments. Underwater organisms, including organisms with soft appearance such as starfish and sea cucumbers, and organisms with hard shell, such as sea snails and crabs, can also be caught harmlessly. In cases where a single 3D-SWHSA is insufficient for capturing objects with unstable centers of gravity or when the capture range is exceeded, the double 3D-SWHSAs can be utilized for cooperative winding. This study affirms the great potential of 3D-SWHSA in diverse marine applications, including but not limited to marine exploration, fishing, and operations.

Probiotics formulation and cancer nanovaccines show synergistic effect in immunotherapy and prevention of colon cancer.

Probiotics play essential roles in immune modulation. Combining probiotics with cancer vaccines potentially can achieve a synergistic effect. To maximize the efficacy of probiotics, proper probiotics formulation is necessary. Herein, Lactobacillus rhamnosus and Bifidobacterium longum are coated with lipid membrane to achieve the goal of losing less activity and bettering colonization in colon. In the subcutaneous transplanted colon cancer mouse model, probiotics formulation showed potent preventive and therapeutic efficacy, and the efficacy could be further improved by combining with cancer nanovaccines. Probiotics formulation can perform as immune adjuvants to enhance the innate immune response or as in-situ cancer vaccines. In the study of preventing chemical-induced orthotopic colon cancer model, probiotics formulation alone efficiently reduced tumor number in colon and the efficacy is improved by combining with cancer nanovaccines. All in all, the studies demonstrated that probiotics formulation can assist to maximize the efficacy of cancer nanovaccines.

Effects of Chinese herbal diet on hematopoiesis, immunity, and intestines of mice exposed to different doses of radiation.

Radiotherapy causes a series of side effects in patients with malignant tumors. Polygonati Rhizoma, Achyranthis Bidentatae Radix, and Epimedii Folium are all traditional Chinese herbs with varieties of functions such as anti-radiation and immune regulation. In this study, the above three herbs were used as a herbal diet to study their effects on the hematopoietic, immune, and intestinal systems of mice exposed to three doses of radiation. Our study showed that the diet had no radiation-protective effect on the hematopoietic and immune systems. However, at the radiation dose of 4 Gy and 8 Gy, the diet showed an obvious radiation-protective effect on intestinal crypts. At the dose of 8 Gy, we also found that the Chinese herbal diet had an anti-radiation effect on reducing the loss of the inhibitory nNOS+ neurons in the intestine. That provides a new diet for relieving the symptoms of hyperperistalsis and diarrhea in patients after radiotherapy.

Incidence and predictive value of social frailty among community-dwelling older adults in Southwest China: A prospective cohort study.

Background: Few studies have focused on the incidence and correlation of social frailty (SF) with adverse health events in Southwest China. This study aims to explore the predictive value of SF for adverse health events. Methods: A 6-year prospective cohort study was employed, a total of 460 community-dwelling older adults aged 65 years and above were analyzed to provide a baseline in 2014. Participants completed two longitudinal follow-ups at 3 (2017, 426 participants involved) and 6 (2020, 359 participants involved) years later. A modified social frailty screening index was used in this study, and adverse health events such as physical frailty (PF) deterioration, disability, hospitalization, falls, and mortality were evaluated. Results: Among these participants in 2014, the median age was 71 years, 41.1% were male, and 71.1% were married or cohabiting, up to 112 (24.3%) of them were classified as SF. It was observed that aging (OR = 1.04, 95% CI = 1.00-1.07, P = 0.047) and having family members die in the past year (OR = 2.60, 95% CI = 0.93-7.25, P = 0.068) were risk factors of SF, whereas having a mate (OR = 0.40, 95% CI = 0.25-0.66, P = 0.000) and having family members to help with care (OR = 0.53, 95% CI = 0.26-1.11, P = 0.092) were protective factors of SF. The cross-sectional study demonstrated that SF was only significantly associated with disability (OR = 12.89, 95% CI = 2.67-62.13, P = 0.001) at wave 1. Baseline SF significantly explained the incidence of mortality at the 3-year (medium-term, OR = 4.89, 95% CI = 2.23-10.71, P = 0.000) and 6-year follow-ups (long-term, OR = 2.22, 95% CI = 1.15-4.28, P = 0.017). Conclusion: SF prevalence was higher in the Chinese older population. Older adults with SF had a significantly increased incidence of mortality at the longitudinal follow-up. Consecutive comprehensive health management of SF (e.g., avoiding living alone and increasing social engagement) is urgently needed for the purposes of early prevention and multidimensional intervention in adverse health events, including disability and mortality.

Guillain-Barre syndrome following COVID-19 vaccines: A review of literature.

Objective: This study aimed to retrospectively analyze reported Guillain-Barré syndrome (GBS) cases that occurred after COVID-19 vaccination. Methods: Case reports of GBS following COVID-19 vaccination that were published before May 14, 2022, were retrieved from PubMed. The cases were retrospectively analyzed for their basic characteristics, vaccine types, the number of vaccination doses before onset, clinical manifestations, laboratory test results, neurophysiological examination results, treatment, and prognosis. Results: Retrospective analysis of 60 case reports revealed that post-COVID-19 vaccination GBS occurred mostly after the first dose of the vaccination (54 cases, 90%) and was common for DNA vaccination (38 cases, 63%), common in middle-aged and elderly people (mean age: 54.5 years), and also common in men (36 cases, 60%). The mean time from vaccination to onset was 12.3 days. The classical GBS (31 cases, 52%) was the major clinical classification and the AIDP subtype (37 cases, 71%) was the major neurophysiological subtype, but the positive rate of anti-ganglioside antibodies was low (7 cases, 20%). Bilateral facial nerve palsy (76% vs 18%) and facial palsy with distal paresthesia (38% vs 5%) were more common for DNA vaccination than for RNA vaccination. Conclusion: After reviewing the literature, we proposed a possible association between the risk of GBS and the first dose of the COVID-19 vaccines, especially DNA vaccines. The higher rate of facial involvement and a lower positive rate of anti-ganglioside antibodies may be a characteristic feature of GBS following COVID-19 vaccination. The causal relationship between GBS and COVID-19 vaccination remains speculative, more research is needed to establish an association between GBS and COVID-19 vaccination. We recommend surveillance for GBS following vaccination, because it is important in determining the true incidence of GBS following COVID-19 vaccination, as well as in the development of a more safer vaccine.

Implantable Thermal Therapeutic Device with Precise Temperature Control Enabled by Foldable Electronics and Heat-Insulating Pads.

Thermal therapy has continued to attract the attention of researchers and clinicians due to its important applications in tumor ablation, wound management, and drug release. The lack of precise temperature control capability in traditional thermal treatment may cause the decrease of therapeutic effect and thermal damage to normal tissues. Here, we report an implantable thermal therapeutic device (ITTD), which offers precise closed loop heating, in situ temperature monitoring, and thermal protection. The ITTD features a multifunctional foldable electronics device wrapped on a heat-insulating composite pad. Experimental and numerical studies reveal the fundamental aspects of the design, fabrication, and operation of the ITTD. In vivo experiments of the ITTD in thermal ablation for antitumor demonstrate that the proposed ITTD is capable of controlling the ablation temperature precisely in real time with a precision of at least 0.7°C and providing effective thermal protection to normal tissues. This proof-of-concept research creates a promising route to develop ITTD with precise temperature control capability, which is highly desired in thermal therapy and other disease diagnosis and treatments.

Epidemiological and clinical features of SARS-CoV-2 cluster infection in Anhui Province, Eastern China.

BACKGROUND: COVID-19 has spread worldwide and become a pandemic. We report the epidemiological and clinical characteristics of cluster infections. METHODS: Data of clustered cases were retrieved from the public health emergency monitoring information system of China. We analyzed the incubation period, generation gap, secondary attack rate, and viral load in various grouped cases. RESULTS: A total of 60 COVID-19 infection clusters including 226 patients and 19 asymptomatic cases involving four generations were analyzed. With the increase of transmission generations, secondary attack rate decreased (P＜0.001) and severity alleviated (P = 0.008). The median incubation period and intergenerational interval were 9 and 6 days, respectively. The secondary attack rate was 7.1% in the index cases, 5.0% in the first generation, 1.0% in the second generation, and 4.7% overall. Severe cases were seen more in the index (13, 65%) and first generation (7, 35%) ones, who had a significantly higher viral load than the mild and moderate ones. CONCLUSIONS: With the increase of transmission generation, secondary infection rate and severity decreased. Severe patients had a higher virus load. Patients in the incubation period and asymptomatic carriers were potential infection sources who might play an important role in transmission.

A multifunctional electronic skin based on patterned metal films for tactile sensing with a broad linear response range.

Electronic skins (e-skins) with multifunctional sensing functions have attracted a lot of attention due to their promising applications in intelligent robotics, human-machine interfaces, and wearable healthcare systems. Here, we report a multifunctional e-skin based on patterned metal films for tactile sensing of pressure and temperature with a broad linear response range by implementing the single sensing mechanism of piezoresistivity, which allows for the easy signal processing and simple device configuration. The sensing pixel features serpentine metal traces and spatially distributed microprotrusions. Experimental and numerical studies reveal the fundamental aspects of the multifunctional tactile sensing mechanism of the e-skin, which exhibits excellent flexibility and wearable conformability. The fabrication approach being compatible with the well-established microfabrication processes has enabled the scalable manufacturing of a large-scale e-skin for spatial tactile sensing in various application scenarios.

Pyruvate accumulation may contribute to acceleration-induced impairment of physical and cognitive abilities: an experimental study.

BACKGROUND: Fatigue can be induced after acceleration exposure, however its mechanism is still unclear. The aim of the present study was to examine whether metabolites' changes can decrease cognitive and physical function after acceleration. METHODS: Graybiel scale and Fatigue Self-rating scale were used to assess the seasickness and fatigue degrees of 87 male seafarers respectively after sailing. To test the effect of pyruvate on cognitive and physical functions, five different doses of pyruvate were administrated into rats. Insulin can reduce the accumulation of pyruvate. To observe the insulin effect on pyruvate, cognitive and physical functions after acceleration, insulin administration or treatment of promoting insulin secretion was used. Physical and cognitive functions were assessed using open field test (OFT), morris water maze (MWM) and loaded swimming test (LST) in animals. RESULTS: Physical and cognitive abilities were decreased obviously, and serum pyruvate increased mostly in human and rats after acceleration. Compared with vehicle group, physical and cognitive abilities were significantly decreased after pyruvate administration. Besides, we found a significant decline in adenosine triphosphate (ATP) concentration and pyruvate dehydrogenase (PDH) activity in the hippocampus, prefrontal cortex, liver, and muscle of rats treated with acceleration or pyruvate injection, while insulin administration or treatment of promoting insulin secretion markedly alleviated this decline and the impairment of physical and cognitive abilities, compared with the control group. CONCLUSION: Our results indicate that pyruvate has a negative effect on physical and cognitive abilities after acceleration. Insulin can inhibit pyruvate accumulation and cognitive and physical function after acceleration exposure.

Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner.

BACKGROUND: Hypoxia is a characteristic of the tumor microenvironments within pancreatic cancer (PC), which has been linked to its malignancy. Recently, hypoxia has been reported to regulate the activity of important carcinogenic pathways by changing the status of histone modification. NOX4, a member of NADPH oxidase (NOX), has been found to be activated by hypoxia and promote cancer progression in several cancers. But whether it is involved in the epigenetic changes of tumor cells induced by hypoxia is still unclear, and its biological roles in PC also need to be explored. METHODS: A hypoxic-related gene signature and its associated pathways in PC were identified by analyzing the pancreatic cancer gene expression data from GEO and TCGA database. Candidate downstream gene (NOX4), responding to hypoxia, was validated by RT-PCR and western blot. Then, we evaluated the relationship between NOX4 expression and clinicopathologic parameters in 56 PC patients from our center. In vitro and in vivo assays were preformed to explore the phenotype of NOX4 in PC. Immunofluorescence, western blot and chromatin immunoprecipitation assays were further applied to search for a detailed mechanism. RESULTS: We quantified hypoxia and developed a hypoxia signature, which was associated with worse prognosis and elevated malignant potential in PC. Furthermore, we found that NADPH oxidase 4 (NOX4), which was induced by hypoxia and upregulated in PC in a HIF1A-independent manner, caused inactivation of lysine demethylase 5A (KDM5A), increased the methylation modification of histone H3 and regulated the transcription of EMT-associated gene_ snail family transcriptional repressor 1 (SNAIL1). This served to promote the invasion and metastasis of PC. NOX4 deficiency repressed hypoxia-induced EMT, reduced expression of H3K4ME3 and impaired the invasion and metastasis of PC cells; however, knockdown of KDM5A reversed the poor expression of H3KEME3 induced by NOX4 deficiency, thereby promoting EMT. CONCLUSIONS: This study highlights the prognostic role of hypoxia-related genes in PC and strong correlation with EMT pathway. Our results also creatively discovered that NOX4 was an essential mediator for hypoxia-induced histone methylation modification and EMT in PC cells.

PPARγ/SOD2 Protects Against Mitochondrial ROS-Dependent Apoptosis via Inhibiting ATG4D-Mediated Mitophagy to Promote Pancreatic Cancer Proliferation.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognosis. Our previous study found that peroxisome proliferator activated receptor gamma (PPARγ) was capable of enhancing glycolysis in PDAC cells. However, whether PPARγ could promote PDAC progression remains unclear. In our present study, PPARγ was positively associated with tumor size and poor prognosis in PDAC patients. Functional assays demonstrated that PPARγ could promote the proliferation of pancreatic cancer cells in vitro and in vivo. Additionally, flow cytometry results showed that PPARγ decreased mitochondrial reactive oxygen species (mitochondrial ROS) production, stabilized mitochondrial membrane potential (MMP) and inhibited cell apoptosis via up-regulating superoxide dismutase 2 (SOD2), followed by the inhibition of ATG4D-mediated mitophagy. Meanwhile, the activation of PPARγ might reduce pancreatic cancer cell stemness to improve PDAC chemosensitivity via down-regulating ATG4D. Thus, these results revealed that PPARγ/SOD2 might protect against mitochondrial ROS-dependent apoptosis via inhibiting ATG4D-mediated mitophagy to promote pancreatic cancer proliferation, further improving PDAC chemosensitivity.

ALDH1A3 Accelerates Pancreatic Cancer Metastasis by Promoting Glucose Metabolism.

Background: The aldehyde dehydrogenase 1 family member A3 (ALDH1A3) is a key enzyme associated with a variety of metabolic processes, including glucose metabolism. We recently uncovered that glucose metabolism played an essential role in promoting metastasis of pancreatic ductal adenocarcinoma (PDAC). As ALDH1A3 labels an aggressive subtype of PDAC, we hypothesized that ALDH1A3 functionally promoted PDAC metastasis via its metabolic effect on glucose metabolism. Methods: Expression of ALDH1A3 was detected in human PDAC tissues by immunohistochemistry. ALDH1A3 was knocked down or overexpressed in PDAC cells by either shRNA or overexpression vector. The functional roles of ALDH1A3 were characterized in vitro and in vivo. Transcriptional profiling via RNA-sequencing was used to explore the possible underlying molecular mechanisms. Glucose uptake, extracellular lactate, and ATP production were measured to access the metabolic influence of ALDH1A3 on PDAC cells. Results: ALDH1A3 was associated with poor prognosis in PDAC patients. Functionally, ALDH1A3 promoted PDAC metastasis in vitro and in vivo. Further studies revealed that ALDH1A3 activated PI3K/AKT/mTOR signaling pathway and its downstream target-PPARγ (peroxisome proliferator-activated receptor gamma). This led to increase the expression of HK2 (hexokinase 2), which subsequently enhanced the glycolysis in PDAC cells. Additionally, the pharmacological inhibition of PPARγ activity in ALDH1A3-positive cells impaired glycolytic genes expression, PI3K/AKT/mTOR activity and cellular glycolysis. Conclusions: ALDH1A3 promotes PDAC metastasis via its metabolic influence on glucose metabolism. PPARγ and its downstream PI3K/AKT/mTOR signaling pathway maybe involved in this process.

Programmable and scalable transfer printing with high reliability and efficiency for flexible inorganic electronics.

Transfer printing that enables heterogeneous integration of materials in desired layouts offers unprecedented opportunities for developing high-performance unconventional electronic systems. However, large-area integration of ultrathin and delicate functional micro-objects with high yields in a programmable fashion still remains as a great challenge. Here, we present a simple, cost-effective, yet robust transfer printing technique via a shape-conformal stamp with actively actuated surface microstructures for programmable and scalable transfer printing with high reliability and efficiency. The shape-conformal stamp features the polymeric backing and commercially available adhesive layer with embedded expandable microspheres. Upon external thermal stimuli, the embedded microspheres expand to form surface microstructures and yield weak adhesion for reliable release. Systematic experimental and computational studies reveal the fundamental aspects of the extraordinary adhesion switchability of stamp. Demonstrations of this protocol in deterministic assemblies of diverse challenging inorganic micro-objects illustrate its extraordinary capabilities in transfer printing for developing high-performance flexible inorganic electronics.

Up-regulated LncRNA-ATB regulates the growth and metastasis of cholangiocarcinoma via miR-200c signals.

BACKGROUND AND OBJECTIVE: Cholangiocarcinoma (CCA) is a highly aggressive neoplasm featured with regional invasiveness and distant metastasis, which often present a phenotype of epithelial-mesenchymal transition (EMT). Long non-coding RNAs (LncRNAs) are dysregulated during carcinogenesis, and up-regulated LncRNA-activated by TGF-ß (Lnc-ATB) supports tumor growth and metastasis via tumor suppressor microRNA 200 (miR-200). However, the role of Lnc-ATB in CCA is unclear. METHODS: CCA tissues and non-cancer tissues (n=30) were used to determine the Lnc-ATB and miR-200a/b/c levels. The functions and mechanisms of Lnc-ATB/miR-200 pathway were determined by knockdown of Lnc-ATB via siRNAs in vitro and in vivo. RESULTS: CCA tissues have increased Lnc-ATB and reduced miR-200a/b/c levels, but the down-regulated miR-200c was most prominent. Up-regulated Lnc-ATB significant negatively correlated with miR-200c and predicted advanced TNM stage and more lymph node metastasis of CCA patients. Knockdown of Lnc-ATB in two CCA cell lines HuCCT1 and RBE increased miR-200c levels. The luciferase reporter assay further confirmed the direct binding site of miR-200c in Lnc-ATB. Inhibition of Lnc-ATB significantly impaired cell vitality and induced apoptosis and G0/G1 arrest, which, however, was rescued by miR-200c inhibitor. The ability of migration of CCA cells was also up-regulated by Lnc-ATB but was suppressed by miR-200c. Mechanistically, the cell cycle-related CCND1/CDK2, apoptosis-related BCL-2/caspase-3 and EMT-related E-cadherin/ZEB1/2 were regulated by Lnc-ATB via miR-200c. Knockdown of Lnc-ATB in vivo up-regulated miR-200c signals to inhibit tumor growth with decreased PCNA expression in tumor tissues, which was restored by miR-200c inhibition. CONCLUSION: Overexpressed Lnc-ATB functioned as an oncogene for CCA growth and metastasis via miR-200 signals.

Soft Elastomers with Programmable Stiffness as Strain-Isolating Substrates for Stretchable Electronics.

Stretchable electronics are of rapidly increasing interest due to their unique ability to function under complex deformations. Strain isolation of stiff functional components from the substrate represents a key challenge in the development of stretchable electronics since their mechanical mismatch may yield undesirable strains to degrade the device performance. The results presented here report an approach to develop a soft strain-isolating polymer substrate with programmable stiffness by spatioselective ultraviolet exposure for stretchable electronics. The approach being compatible with the well-established lithographic process reduces the fabrication complexity significantly and offers a simple yet robust strain-isolation mechanism to ensure the system stretchability of more than 100%. Combined experimental and numerical studies reveal the fundamental aspects of the design, fabrication, and operation of the strain-isolating substrate. Demonstration of this concept in a stretchable inorganic metal-based resistive temperature sensor and a stretchable organic photodiode array with unusually high performance shows the simplicity of the approach and the robustness in strain isolation in both component and device levels. This type of strain-isolation design not only creates promising routes for potential scalable manufacturing of stretchable electronics but also engineering opportunities for stretchable electronics involving the integration of various functional components, which require the quantitative control of the strain levels to achieve optimal performance.

Elevated FAM3C promotes cell epithelial- mesenchymal transition and cell migration in gastric cancer.

BACKGROUND: Tumor metastasis is an important factor in treatment failure for advanced gastric cancer. Family with sequence similarity 3 member C (FAM3C) is known to play a critical role in inducing epithelial-mesenchymal transition in several cancer types, while its role in gastric cancer is unidentified. The aim of this study was to investigate the role of FAM3C in gastric cancer and provide new information on the receptor tyrosine-kinase pathway and cytokine-based therapies. METHODS: FAM3C expression was tested in human gastric cancer tissue and adjacent normal mucosa, and the prognostic effect of FAM3C was analyzed in data from the Cancer Genome Atlas (TCGA). The role of FAM3C in gastric cancer proliferation and metastasis was investigated in vitro and in vivo. Western blot analysis and immunofluorescence were used to detect the underlying mechanisms. RESULTS: FAM3C expression was increased in gastric cancer tissue and showed cytoplasmic distribution. Gastric cancer patients with FAM3C overexpression had significantly worse prognoses based on TCGA data. In the gastric cancer cell lines MKN45 and AGS, knockdown of FAM3C dramatically attenuated cell migration, but had almost no influence on proliferation, while exogenous FAM3C promoted cell migration in a cell line with low FAM3C expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of TCGA data showed that FAM3C was mainly associated with genes involved in focal adhesion, extracellular matrix-receptor interactions and the PI3K-Akt signaling pathway. Knockdown of FAM3C in gastric cancer cell lines significantly suppressed epithelial-mesenchymal transition, as demonstrated by increased expression of E-cadherin and decreased expression of Snail and Slug. Furthermore, knockdown of FAM3C strongly suppressed activation of the PI3K-Akt signaling pathway. Finally, we confirmed that FAM3C knockdown significantly decreased metastatic lesions in vivo. CONCLUSION: Our study demonstrated that FAM3C can promote gastric cancer metastasis both in vitro and in vivo. FAM3C should be taken into consideration for gastric cancer treatments involving inhibition of the ligands and downstream pathways of receptor tyrosine kinases.

The Dynamic Trends of Urinary LH and FSH Assayed by ICMA During Triptorelin Stimulation Tests in Girls - a Pilot Study.

BACKGROUND: Gonadotropin-releasing hormone stimulation test is a gold standard for evaluating the function of the hypothalamic-pituitary-gonadal axis (HPGA) in children. These tests are usually uncomfortable because of multi-venipunctures. A urine specimen is a good alternative because it is noninvasive and convenient. More studies have shown the correlation between sera and urine LH and FSH levels under different physiological and pathological conditions. METHODS: The study investigated the dynamic trends of urine LH (uLH) and FSH (uFSH) assayed by immunochemiluminometric assays (ICMA) during triptorelin stimulation tests in girls. The triptorelin stimulation tests were performed in 52 girls with disorders of puberty. The time 0 hour was regarded as the start time of the test (8:30 am). The day before the tests, urine samples were collected at 12 hours diurnal (-24 hours ~ -12 hours) and nocturnal (-12 hours ~ 0 hour) time points. On the day of the testing, the first 12 hours (0 hour ~ 12 hours), the second 12 hours (12 hours ~ 24 hours), the third 12 hours (24 hours ~ 36 hours), the fourth 12 hours (36 hours ~ 48 hours), the third and fourth overnight urine samples were also collected. The LH and FSH levels were assayed by ICMA, and uLH and uFSH were corrected for creatinine (Cr). RESULTS: The HPGA in 41 girls was activated but it was nonactivated in 11 girls. In girls with HPGA activated, uLH/Cr or uFSH/Cr was significantly elevated within 24 hours, and gradually dropped to baseline after 48 hours. When HPGA was nonactivated in girls, there were the same dynamic trends but much lower amplitude of uLH/Cr or uFSH/Cr, which dropped to baseline after 24 hours. CONCLUSIONS: The stimulated uLH and uFSH assayed by ICMA are valuable for evaluating the function of HPGA in girls, and the valuable time window is within 24 hours.