Germline SDHB and SDHD Mutations in Pheochromocytoma and Paraganglioma Patients

Pheochromocytoma and paragangliomas (PCC/PGL) are neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and sympathetic/parasympathetic ganglia, respectively. Of clinical relevance regarding diagnosis is the highly variable presentation of symptoms in PCC/PGL patients. To date, the clear-cut correlations between the genotypes and phenotypes of PCC/PGL have not been entirely established. In this study, we reviewed the medical records of PCC/PGL patients with pertinent clinical, laboratory and genetic information. Next-generation sequencing (NGS) performed on patient samples revealed specific germline mutations in the SDHB (succinate dehydrogenase complex iron-sulfur subunit B) and SDHD（succinate dehydrogenase complex subunit D) genes and these mutations were validated by Sanger sequencing. Of the 119 patients, two were identified with SDHB mutation and one with SDHD mutation. Immunohistochemical (IHC) staining was used to analyze the expression of these mutated genes. The germline mutations identified in the SDH genes were: c343C\u3eT and c.541-542A\u3eG in the SDHB gene and c.334-337delACTG in the SDHD gene. IHC staining of tumors from the c.343C\u3eT and c.541-2A\u3eG carriers showed positive expression of SDHB. Tumors from the c.334-337delACTG carrier showed no expression of SDHD and a weak diffused staining pattern for SDHB. We strongly recommend genetic testing for suspected PCC/PGL patients with a positive family history, early onset of age, erratic hypertension, recurrence or multiple tumor sites and loss of SDHB and/or SDHD expression. Tailored personal management should be conducted once a patient is confirmed as an SDHB and/or SDHD mutation carrier or diagnosed with PCC/PGL

In Situ TEM Study of the Degradation of PbSe Nanocrystals in Air

PbSe nanocrystals have attracted widespread attention due to a variety of potential applications. However, the practical utility of these nanocrystals has been hindered by their poor air stability, which induces undesired changes in the optical and electronic properties. An understanding of the degradation of PbSe nanocrystals when they are exposed to air is critical for improving the stability and enhancing their applications. Here, we use in situ transmission electron microscopy (TEM) with an environmental cell connected to air to study PbSe nanocrystal degradation triggered by air exposure. We have also conducted a series of complementary studies, including in situ environmental TEM study of PbSe nanocrystals exposed to pure oxygen and PbSe nanocrystals in H2O using a liquid cell, and ex situ experiments, such as O2 plasma treatment and thermal heating of PbSe nanocrystals under different air exposure. Our in situ observations reveal that when PbSe nanocrystals are exposed to air (or oxygen) under electron beam irradiation, they experience a series of changes, including shape evolution of individual nanocrystals with the cuboid intermediates, coalescence between nanocrystals, and formation of PbSe thin films through drastic solid-state fusion. Further studies show that the PbSe thin films transform into an amorphous Pb rich phase or eventually pure Pb, which suggest that Se reacts with oxygen and can be evaporated under electron beam illumination. These various in situ and ex situ experimental results indicate that PbSe nanocrystal degradation in air is initiated by the dissociation and removal of ligands from the PbSe nanocrystal surface

Metabolic reprogramming of three major nutrients in platinum-resistant ovarian cancer

Metabolic reprogramming is a phenomenon in which cancer cells alter their metabolic pathways to support their uncontrolled growth and survival. Platinum-based chemotherapy resistance is associated with changes in glucose metabolism, amino acid metabolism, fatty acid metabolism, and tricarboxylic acid cycle. These changes lead to the creation of metabolic intermediates that can provide precursors for the biosynthesis of cellular components and help maintain cellular energy homeostasis. This article reviews the research progress of the metabolic reprogramming mechanism of platinumbased chemotherapy resistance caused by three major nutrients in ovarian cancer

LSD1 Promotes Bladder Cancer Progression by Upregulating LEF1 and Enhancing EMT.

Epithelial-to-mesenchymal transition (EMT) is one of the important underlying molecular mechanisms for most types of cancers including bladder cancer. The precise underlying molecular mechanism in EMT-mediated bladder cancer progression is far from completed. LSD1, a histone lysine-specific demethylase, is known to promote cancer cell proliferation, metastasis, and chemoresistance. We found in this study that LSD1 is highly upregulated in bladder cancer specimens, especially those underwent chemotherapy, and the elevated levels of LSD1 are highly associated with bladder cancer grades, metastasis status, and prognosis. Inhibiting or knockdown LSD1 repressed not only EMT process but also cancer progression. Mechanistically, LSD1 complexes with β-catenin to transcriptionally upregulate LEF1 and subsequently enhances EMT-mediated cancer progression. More importantly, LSD1 specific inhibitor GSK2879552 is capable of repressing tumor progression in patient-derived tumor xenograft. These findings altogether suggest that LSD1 can serve as not only a prognostic biomarker but also a promising therapeutic target in bladder cancer treatment

Ultrasensitive piezoelectric sensor based on two-dimensional Na2Cl crystals with periodic atom vacancies

Pursuing ultrasensitivity of pressure sensors has been a long-standing goal. Here, we report a piezoelectric sensor that exhibits supreme pressure-sensing performance, including a peak sensitivity up to 3.5*10^6 kPa^-1 in the pressure range of 1-100 mPa and a detection limit of less than 1 mPa, superior to the current state-of-the-art pressure sensors. These properties are attributed to the high percentage of periodic atom vacancies in the two-dimensional Na2Cl crystals formed within multilayered graphene oxide membrane in the sensor, which provides giant polarization with high stability. The sensor can even clearly detect the airflow fluctuations surrounding a flapping butterfly, which have long been the elusive tiny signals in the famous "butterfly effect". The finding represents a step towards next-generation pressure sensors for various precision applications

A Renal Cell Carcinoma with Biallelic Somatic TSC2 Mutation: Clinical Study and Literature Review.

OBJECTIVES: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC). METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted. RESULTS: Two novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which leads to constitutive activation of mTORC1 pathway and ultimately cause the development of RCC. CONCLUSIONS: Detecting TSC2 mutation in patients with early RCC onset would be beneficial and mTOR inhibitor could be a therapeutic option for TSC2 mutation-induced RCC

Pancreatic Cancer Epidemiology, Detection, and Management

PC (pancreatic cancer) is the fourth most common cause of death due to cancer worldwide. The incidence and mortality rates have been increasing year by year worldwide, and this review has analyzed the most recent incidence and mortality data for pancreatic cancer occurrence in China. Several possible risk factors have been discussed here, involving known established risk factors and novel possible risk factors. The development of this cancer is a stepwise progression through intraepithelial neoplasia to carcinoma. Though early and accurate diagnosis is promising based on a combination of recent techniques including tumor markers and imaging modalities, lacking early clinical symptoms makes the diagnosis late. Correct staging is critical because treatment is generally based on this parameter. Treatment options have improved throughout the last decades. However, surgical excision remains the primary therapy and efficacy of conventional chemoradiotherapy for PC is limited. Recently, some novel new therapies have been developed and will be applied in clinics soon. This review will provide an overview of pancreatic cancer, including an understanding of the developments and controversies

Germline SDHB and SDHD mutations in pheochromocytoma and paraganglioma patients

Pheochromocytoma and paragangliomas (PCC/PGL) are neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and sympathetic/parasympathetic ganglia, respectively. Of clinical relevance regarding diagnosis is the highly variable presentation of symptoms in PCC/PGL patients. To date, the clear-cut correlations between the genotypes and phenotypes of PCC/PGL have not been entirely established. In this study, we reviewed the medical records of PCC/PGL patients with pertinent clinical, laboratory and genetic information. Next-generation sequencing (NGS) performed on patient samples revealed specific germline mutations in the SDHB (succinate dehydrogenase complex iron-sulfur subunit B) and SDHD (succinate dehydrogenase complex subunit D) genes and these mutations were validated by Sanger sequencing. Of the 119 patients, two were identified with SDHB mutation and one with SDHD mutation. Immunohistochemical (IHC) staining was used to analyze the expression of these mutated genes. The germline mutations identified in the SDH genes were c343C>T and c.541-542A>G in the SDHB gene and c.334-337delACTG in the SDHD gene. IHC staining of tumors from the c.343C>T and c.541-2A>G carriers showed positive expression of SDHB. Tumors from the c.334-337delACTG carrier showed no expression of SDHD and a weak diffused staining pattern for SDHB. We strongly recommend genetic testing for suspected PCC/PGL patients with a positive family history, early onset of age, erratic hypertension, recurrence or multiple tumor sites and loss of SDHB and/or SDHD expression. Tailored personal management should be conducted once a patient is confirmed as an SDHB and/or SDHD mutation carrier or diagnosed with PCC/PGL

In situ interface engineering for probing the limit of quantum dot photovoltaic devices.

Quantum dot (QD) photovoltaic devices are attractive for their low-cost synthesis, tunable band gap and potentially high power conversion efficiency (PCE). However, the experimentally achieved efficiency to date remains far from ideal. Here, we report an in-situ fabrication and investigation of single TiO2-nanowire/CdSe-QD heterojunction solar cell (QDHSC) using a custom-designed photoelectric transmission electron microscope (TEM) holder. A mobile counter electrode is used to precisely tune the interface area for in situ photoelectrical measurements, which reveals a strong interface area dependent PCE. Theoretical simulations show that the simplified single nanowire solar cell structure can minimize the interface area and associated charge scattering to enable an efficient charge collection. Additionally, the optical antenna effect of nanowire-based QDHSCs can further enhance the absorption and boost the PCE. This study establishes a robust 'nanolab' platform in a TEM for in situ photoelectrical studies and provides valuable insight into the interfacial effects in nanoscale solar cells