TG-interacting factor 1 regulates mitotic clonal expansion during adipocyte differentiation.

Obesity is one of the significant health challenges in the world and is highly associated with abnormal adipogenesis. TG-interacting factor 1 (TGIF1) is essential for differentiating murine adipocytes and human adipose tissue-derived stem cells. However, the mode of action needs to be better elucidated. To investigate the roles of TGIF1 in differentiation in-depth, CRISPR/Cas9 knockout technology was performed to generate TGIF1-silenced preadipocytes. The absence of TGIF1 in 3 T3-F442A preadipocytes abolished lipid accumulation throughout the differentiation using Oil Red O staining. Conversely, we established 3 T3-F442A preadipocytes stably expressing TGIF1 and doxycycline-inducible TGIF1 in TGIF1-silenced 3 T3-F442A preadipocytes. Remarkably, the induction of TGIF1 by doxycycline during the initial differentiation phase successfully promoted lipid accumulation in TGIF1-silenced 3 T3-F442A cells. We further explored the mechanisms of TGIF1 in early differentiation. We demonstrated that TGIF1 promoted the mitotic clonal expansion via upregulation of CCAAT/enhancer-binding proteins ß expression, interruption with peroxisome proliferators activated receptor γ downstream regulation, and inhibition of p27kip1 expression. In conclusion, we strengthen the pivotal roles of TGIF1 in early differentiation, which might contribute to resolving obesity-associated metabolic syndromes.

Phosphorylation of TG-interacting factor 1 at carboxyl-terminal sites in response to insulin regulates adipocyte differentiation.

TG-interacting factor 1 (TGIF1) contributes to the differentiation of murine white preadipocyte and human adipose tissue-derived stem cells; however, its regulation is not well elucidated. Insulin is a component of the adipogenic cocktail that induces ERK signaling. TGIF1 phosphorylation and sustained stability in response to insulin were reduced through the use of specific MEK inhibitor U0126. Mutagenesis at T235 or T239 residue of TGIF1 in preadipocytes led to dephosphorylation of TGIF1. The reduced TGIF1 stability resulted in an increase in p27kip1 expression, a decrease in phosphorylated Rb expression and cellular proliferation, and a reduced accumulation of lipids compared to the TGIF1-overexpressed cells. These findings highlight that insulin/ERK-driven phosphorylation of the T235 or T239 residue at TGIF1 is crucial for adipocyte differentiation.

Cervical Conjoined Nerve Root During Posterior Percutaneous Endoscopic Cervical Diskectomy.

Cervical conjoined nerve root is rare, and medical imaging, such as magnetic resonance imaging and computed tomography, cannot give an accurate preoperative diagnosis.1 Treatment of cervical radiculopathy with root anomaly can be challenging. We report here a case of cervical conjoined nerve root with a 2-dimensional video. A 41-year-old woman without systemic disease presented with a 2-month history of neck and bilateral shoulder pain, upper back tightness, and left upper limb painful numbness, especially of the first to third fingers. The visual analog scale scores of the neck and left upper limb were 4 and 8, respectively. The Neck Disability Index was 26. The diagnosis of retrolisthesis at C5-C6 and cervical disk herniation with severe neuroforaminal narrowing at the left C5-C6 and C6-C7 levels were made with radiographs and magnetic resonance imaging. Posterior percutaneous endoscopic cervical diskectomy at the left C5-C6 and C6-C7 levels via an interlaminar shoulder approach was performed. During operation, a left-sided conjoined nerve root at the C6-C7 level was found (Video 1). Upon removal of a calcified disk and osteophytes at the C6-C7 level, the dura was torn slightly with traction without nerve root exposure or cerebrospinal fluid leakage. The 3-month postoperative follow-up visual analog scale scores of the neck and left upper limb were 0 and 0, respectively. The 3-month postoperative follow-up Neck Disability Index was 1. Posterior percutaneous endoscopic cervical diskectomy has become a favored treatment for cervical disk herniation because it offers sufficient decompression, smaller incisions, minimal blood loss, shorter hospital stay, and less postoperative pain.2,3 Nonetheless, if unexpected variation of the nerve root is noted during decompressive procedures, iatrogenic nerve root injury is a risk. Seven cases of cervical nerve root anomalies have been reported; all were found during posterior cervical surgery, which may indicate that the posterior approach provides better visualization of nerve root variants, especially in endoscopic surgery.4.

CDCP1 (CUB domain containing protein 1) is a potential urine-based biomarker in the diagnosis of low-grade urothelial carcinoma.

Urine-based cytology is non-invasive and widely used for clinical diagnosis of urothelial carcinoma (UC), but its sensitivity is less than 40% for low-grade UC detection. As such, there is a need for new diagnostic and prognostic biomarkers of UC. CUB domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein highly expressed in various cancers. Using tissue array analysis, we demonstrated that CDCP1 expression in UC patients (n = 133), especially in those with low-grade UC, was significantly higher than in 16 normal persons. In addition, CDCP1 expression in urinary UC cells could also be detected by using immunocytochemistry method (n = 11). Furthermore, in 5637-CD cells, overexpression of CDCP1 affected the expression of epithelial mesenchymal transition-related markers and increased matrix metalloproteinase 2 expression and migration ability. Conversely, the knockdown of CDCP1 in T24 cells had the opposite effects. Using specific inhibitors, we demonstrated the involvement of c-Src/PKCδ signaling in the CDCP1-regulated migration of UC. In conclusion, our data suggest that CDCP1 contributes to the malignant progression of UC and may have the potential as a urine-based biomarker for detecting low-grade UC. However, a cohort study needs to be conducted.

First-Principles Assessment of CdTe as a Tunnel Barrier at the α-Sn/InSb Interface.

Majorana zero modes, with prospective applications in topological quantum computing, are expected to arise in superconductor/semiconductor interfaces, such as ß-Sn and InSb. However, proximity to the superconductor may also adversely affect the semiconductor's local properties. A tunnel barrier inserted at the interface could resolve this issue. We assess the wide band gap semiconductor, CdTe, as a candidate material to mediate the coupling at the lattice-matched interface between α-Sn and InSb. To this end, we use density functional theory (DFT) with Hubbard U corrections, whose values are machine-learned via Bayesian optimization (BO) [ npj Computational Materials 2020, 6, 180]. The results of DFT+U(BO) are validated against angle resolved photoemission spectroscopy (ARPES) experiments for α-Sn and CdTe. For CdTe, the z-unfolding method [ Advanced Quantum Technologies 2022, 5, 2100033] is used to resolve the contributions of different kz values to the ARPES. We then study the band offsets and the penetration depth of metal-induced gap states (MIGS) in bilayer interfaces of InSb/α-Sn, InSb/CdTe, and CdTe/α-Sn, as well as in trilayer interfaces of InSb/CdTe/α-Sn with increasing thickness of CdTe. We find that 16 atomic layers (3.5 nm) of CdTe can serve as a tunnel barrier, effectively shielding the InSb from MIGS from the α-Sn. This may guide the choice of dimensions of the CdTe barrier to mediate the coupling in semiconductor-superconductor devices in future Majorana zero modes experiments.

Non-invasive brain neuromodulation techniques for chronic low back pain.

Structural and functional changes of the brain occur in many chronic pain conditions, including chronic low back pain (CLBP), and these brain abnormalities can be reversed by effective treatment. Research on the clinical applications of non-invasive brain neuromodulation (NIBS) techniques for chronic pain is increasing. Unfortunately, little is known about the effectiveness of NIBS on CLBP, which limits its application in clinical pain management. Therefore, we summarized the effectiveness and limitations of NIBS techniques on CLBP management and described the effects and mechanisms of NIBS approaches on CLBP in this review. Overall, NIBS may be effective for the treatment of CLBP. And the analgesic mechanisms of NIBS for CLBP may involve the regulation of pain signal pathway, synaptic plasticity, neuroprotective effect, neuroinflammation modulation, and variations in cerebral blood flow and metabolism. Current NIBS studies for CLBP have limitations, such as small sample size, relative low quality of evidence, and lack of mechanistic studies. Further studies on the effect of NIBS are needed, especially randomized controlled trials with high quality and large sample size.

Maintaining the Quality of Mechanical Thrombectomy after Acute Ischemic Stroke in COVID(-)19 Patients.

The COVID-19 pandemic has become increasingly worse worldwide since it was discovered in China in late December 2019. Easy contact transmission between people and a low to moderate mortality rate may cause failure in medical health services if there is no proper personal protective equipment for personnel. During the pandemic, patients with acute ischemic stroke with large-vessel occlusion who required immediate treatment through mechanical thrombectomy (MT) were still being sent to the emergency room. Knowing how to maintain effective treatment standards has become our concern. We used a retrospective, single-center study to select COVID-19 (-) patients with acute ischemic stroke undergoing mechanical thrombectomy during the years 2020-2021. Patients with acute ischemic stroke with large-vessel occlusion received mechanical thrombectomy were compared with patients admitted from December 2020 to May 2021 (the pre-COVID-19 group) and those from June 2021 to November 2021 (the during COVID-19 group). Furthermore, the time disparity of mechanical thrombectomy was compared between these two groups. Of patients confirmed with acute ischemic stroke (AIS) with large-vessel occlusion (LVO) during the study period, 62 were included. Compared with the pre-COVID-19 group (34 patients; median age, 70.5 years), the during COVID-19 group (28 patients; median age, 71.5 years) showed no major median time difference in door-to-computed-tomography-angiography (CTA) time (19.0 min vs. 20.0 min, p = 0.398) and no major median time difference in door-to-groin-puncture time (118.0 min vs. 109.0 min, p = 0.281). In our study, with a prepared protocol for the pandemic having been established in the healthcare system, we could see no difference between the pre-pandemic and during-pandemic time periods when using mechanical thrombectomy to treat COVID-19 (-) patients of AIS with LVO. By means of a quick-PCR test during triage, there was no time delay to perform MT or any lowering of safety protocol for workers in the healthcare system.

pH Measurement at Elevated Temperature with Vessel Gate and Oxygen-Terminated Diamond Solution Gate Field Effect Transistors.

Diamond has many appealing properties, including biocompatibility, ease of surface modification, and chemical-physical stability. In this study, the temperature dependence of the pH-sensitivity of a oxygen-terminated boron-doped diamond solution gate FET (C-O BDD SGFET) is reported. The C-O BDD SGFET operated in an electrolyte solution at 95 °C. At 80 °C, the pH sensitivity of C-O BDD SGFET dropped to 4.27 mV/pH. As a result, we succeeded in developing a highly sensitive pH sensing system at -54.6 mV/pH at 80 °C by combining it with a highly pH sensitive stainless-steel vessel.

Gemcitabine-induced Gli-dependent activation of hedgehog pathway resists to the treatment of urothelial carcinoma cells.

Patients with urothelial carcinoma (UC) experience gemcitabine resistance is a critical issue. The role of hedgehog pathway in the problem was explored. The expressions of phospho-AKTser473, phospho-GSK3ßser9 and Gli2 were up-regulated in gemcitabine-resistant NTUB1 (NGR) cells. Without hedgehog ligands, Gli proteins can be phosphorylated by GSK3ß kinase to inhibit their downstream regulations. Furthermore, the GSK3ß kinase can be phosphorylated by AKT at its Ser9 residue to become an inactive kinase. Therefore, overexpression of AKT1, Flag-GSKS9D (constitutively inactive form) or active Gli2 (GLI2ΔN) in NTUB1 cells could activate Gli2 pathway to enhance migration/invasion ability and increase gemcitabine resistance, respectively. Conversely, overexpression of Flag-GSKS9A (constitutively active form) or knockdown of Gli2 could suppress Gli2 pathway, and then reduce gemcitabine resistance in NGR cells. Therefore, we suggest gemcitabine-activated AKT/GSK3ß pathway can elicit Gli2 activity, which leads to enhanced migration/invasion ability and resistance to gemcitabine therapy in UC patients. The non-canonical hedgehog pathway should be evaluated in the therapy to benefit UC patients.

Controlling magnetoresistance by tuning semimetallicity through dimensional confinement and heteroepitaxy.

Controlling electronic properties via band structure engineering is at the heart of modern semiconductor devices. Here, we extend this concept to semimetals where, using LuSb as a model system, we show that quantum confinement lifts carrier compensation and differentially affects the mobility of the electron and hole-like carriers resulting in a strong modification in its large, nonsaturating magnetoresistance behavior. Bonding mismatch at the heteroepitaxial interface of a semimetal (LuSb) and a semiconductor (GaSb) leads to the emergence of a two-dimensional, interfacial hole gas. This is accompanied by a charge transfer across the interface that provides another avenue to modify the electronic structure and magnetotransport properties in the ultrathin limit. Our work lays out a general strategy of using confined thin-film geometries and heteroepitaxial interfaces to engineer electronic structure in semimetallic systems, which allows control over their magnetoresistance behavior and simultaneously provides insights into its origin.

Design and Characterisation of a Fast Steering Mirror Compensation System Based on Double Porro Prisms by a Screw-Ray Tracing Method.

This study proposes a novel FSM compensation system for four degrees of freedom (DOF) laser errors compensation, which has the advantage of shorter optical path length, fewer elements and an easier set-up process, meaning that it can be used at different locations. A commercial software, Zemax, is used to evaluate the function of the proposed FSM compensation system and the mathematical modelling of the proposed FSM compensation system is established by using a skew-ray tracing method. Finally, the proposed FSM compensation system is then verified experimentally using a laboratory-built prototype and the result shows that the proposed FSM compensation system achieves the ability to compensate the 4 DOF of the laser source.

p-GaN/n-ZnO nanorods: the use of graphene nanosheets composites to increase charge separation in self-powered visible-blind UV photodetectors.

ZnO-based heterojunctions have found applications as self-powered ultraviolet photodetectors (PDs). However, high doping levels are not compatible with high mobility for metallic doped ZnO-based PDs so further development has been inhibited. This study demonstrates a method to increase the open-circuit voltage (V oc) that allows keeping a sufficiently high level of mobility of ZnO, using a ZnO nanorod/GaN heterojunction that incorporates graphene nanosheets as the active layer. These hybrid PDs have triple the value for V oc of PDs that have only pure ZnO and better exhibit photo-response characteristics. The results of surface Kelvin probe microscopy and x-ray photoelectron spectrometer show that the complex defects that occur because Zn interstitials form a shallow donor in ZnO are mainly responsible for the increase in the value of V oc. Using this functional nanostructure as an active layer represents a new method for the manufacture of high-performance self-powered PDs.

Proteomics displays cytoskeletal proteins and chaperones involvement in Hedyotis corymbosa-induced photokilling in skin cancer cells.

Photodynamic therapy was found to be an effective therapy for local malignant tumors. This study demonstrated that 80 µg/ml Hedyotis corymbosa extracts with 0.8 J/cm(2) fluence dose caused M21 skin cancer cell death. Photoactivated H. corymbosa-induced M21 cell death is a typical apoptosis that is accompanied by nuclear condensation, externalization of phosphatidylserine and the changes in protein expression of apoptosis-related proteins, such as Bcl-2 and caspase family members. This study applied 2D electrophoresis to analyse the proteins involved in the photoactivated H. corymbosa-induced M21 cell apoptosis. We found 12 proteins to be markedly changed. According to the results of protein sequence analysis of these altered protein spots, we identified that the expression of cytoskeletal proteins and chaperones were involved in the photoactivated H. corymbosa-induced M21 cell apoptosis. We further demonstrated that photoactivated H. corymbosa caused a significant effect on the cytoskeleton distribution and mitochondrial activity in M21 cells. Based on the above findings, this study characterized the effects and mechanisms of the photoactivated H. corymbosa-induced apoptosis in M21 skin cancer cells.

Rottlerin Inhibits Lonicera japonica-Induced Photokilling in Human Lung Cancer Cells through Cytoskeleton-Related Signaling Cascade.

This study demonstrated that many apoptotic signaling pathways, such as Rho family, PKC family, MAP kinase family, and mitochondria-mediated apoptotic pathway, were triggered by Lonicera japonica extracts and irradiation in CH27 cells. Rottlerin, a PKCδ -selective inhibitor, reversed the photoactivated Lonicera japonica extract-induced decrease in PKCδ protein expression and change in cell morphology in this study. In addition, rottlerin inhibited the photoactivated Lonicera japonica-induced decrease in protein expression of Ras, ERK, p38, PKCα, and PKCε, which are the kinases of prosurvival signaling pathway. We also demonstrated that pretreatment with rottlerin prevented actin microfilaments and microtubules from damage during the photoactivated Lonicera japonica-induced CH27 cell death. Furthermore, the promotion of the cytoskeleton-related signaling cascade following rottlerin by upregulation of cytoskeleton-related mediators (p38, HSP27, FAK, paxillin, and tubulin) and molecules of downstream of F-actin (mitochondria-mediated apoptosis pathway) reduces CH27 cell death, indicating that cytoskeleton is the potential target in the photoactivated Lonicera japonicaextract-induced photokilling of CH27 cells.

Clarification of the phenotypic characteristics and anti-tumor activity of Hedyotis diffusa.

Hedyotis diffusa Willd. (Rubiaceae) is an important folk herb used to prevent and cure hepatitis and liver cancer in Taiwan. For differentiation of H. diffusa from counterfeits, macroscopic and microscopic characters of H. diffusa, H. corymbosa and H. tenelliflora were examined in this study. According to Trypan blue exclusion assay and Western blot analysis, H. diffusa had a significant inhibition of cell growth and induction of cell apoptosis in COLO 205 (colon cancer), Hep 3B (hepatocellular carcinoma) and H460 (lung cancer) cell lines. This study also used high-performance liquid chromatography (HPLC) to determine the quality control of H. diffusa. The HPLC data showed that ursolic and oleanolic acid are the components of the H. diffusa, consisting of approximately 4.66-4.80% and 1.86-1.96%, respectively. Our study also demonstrated that ursolic acid has significant anti-tumor activity in COLO 205, Hep 3B and H460 cancer cells.