Electrically Controllable Kondo Correlation in Spin-Orbit-Coupled Quantum Point Contacts.

Integrating the Kondo correlation and spin-orbit interactions, each of which have individually offered unprecedented means to manipulate electron spins, in a controllable way can open up new possibilities for spintronics. We demonstrate electrical control of the Kondo correlation by coupling the bound spin to leads with tunable Rashba spin-orbit interactions, realized in semiconductor quantum point contacts. We observe a transition from single to double peak zero-bias anomalies in nonequilibrium transport-the manifestation of the Kondo effect-indicating a controlled Kondo spin reversal using only spin-orbit interactions. Universal scaling of the Kondo conductance is demonstrated, implying that the spin-orbit interactions could enhance the Kondo temperature. A theoretical model based on quantum master equations is also developed to calculate the nonequilibrium quantum transport.

Risk factors that predict major amputations and amputation time intervals for hospitalised diabetic patients with foot complications.

Diabetes-related lower extremity amputations are an enormous burden on global health care and social resources because of the rapid worldwide growth of the diabetic population. This research aimed to determine risk factors that predict major amputation and analyse the time interval from first hospitalisation to amputation by using standard management protocols and Kaplan-Meier survival curves. Data from 246 patients with diabetes mellitus and diabetic foot ulcers from the Division of Plastic and Reconstructive Surgery of the Department of Surgery at XXX Hospital between January 2016 and May 2020 were analysed. Univariate and multivariate analyses of 44 potential risk factors, including invasive ulcer depth and C-reactive protein levels, showed statistically significant differences for those at increased risk for major amputation. The median time from hospitalisation to lower extremity amputation was approximately 35 days. Most patients with abnormal C-reactive protein levels and approximately 70% of patients with ulcers invading the bone were at risk for lower extremity amputations within 35 days. Therefore, invasive ulcer depth and C-reactive protein levels are significant risk factors. Other potential risk factors for major amputation and the time intervals from first hospitalisation to amputation should be analysed to establish further prediction strategies.

Enforced C-Src Activation Causes Compartmental Dysregulation of PI3K and PTEN Molecules in Lipid Rafts of Tongue Squamous Carcinoma Cells by Attenuating Rac1-Akt-GLUT-1-Mediated Sphingolipid Synthesis.

Pharmacologic intervention to affect the membrane lipid homeostasis of lipid rafts is a potent therapeutic strategy for cancer. Here we showed that gallic acid (GA) caused the complex formation of inactive Ras-related C3 botulinum toxin substrate 1 (Rac1)-phospho (p)-casein kinase 2 α (CK2α) (Tyr 255) in human tongue squamous carcinoma (TSC) cells, which disturbed the lipid raft membrane-targeting of phosphatidylinositol 3-kinase (PI3K)-Rac1-protein kinase B (Akt) signal molecules by inducing the association of p110α-free p85α with unphosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN) in lipid rafts. The effects on induction of inactive Rac1-p-CK2α (Tyr 255) complex formation and attenuation of p-Akt (Ser 473), GTP-Rac1, glucose transporter-1 (GLUT-1) lipid raft membrane-targeting, and cell invasive activity by GA were counteracted either by CK2α short hairpin RNA or cellular-Src (c-Src) inhibitor PP1. PP1 treatment, GLUT-1 or constitutively active Rac1 ectopic-expression blocked GA-induced decreases in cellular glucose, sphingolipid and cholesterol of lipid raft membranes, p85α-p110α-GTP-Rac1 complexes, glucosylceramide synthase activity and increase in ceramide and p110α-free p85α-PTEN complex levels of lipid raft membranes, which reversed the inhibition on matrix metalloproteinase (MMP)-2/-9-mediated cell invasion induced by GA. Using transient ectopic expression of nuclear factor-kappa B (NF-κB) p65, MMP-2/-9 promoter-driven luciferase, and NF-κB-dependent luciferase reporter genes and NF-κB specific inhibitors or Rac1 specific inhibitor NSC23766, we confirmed that an attenuation of Rac1 activity by GA confers inhibition of NF-κB-mediated MMP-2/-9 expression and cell invasion. In conclusion, GA-induced c-Src activation is a key inductive event for the formation of inactive Rac1-p-CK2α (Tyr 255) complexes, which disturbed lipid raft compartment of PI3K and PTEN molecules by impairing Akt-regulated GLUT-1-mediated sphingolipid synthesis, and finally resulting in inhibition of TSC cell invasion.

Self-Assembled Chiral Gold Supramolecules with Efficient Laser Absorption for Enantiospecific Recognition of Carnitine.

Stereospecific recognition of chiral molecules is ubiquitous in chemical and biological systems, thus leading to strong demand for the development of enantiomeric drugs, enantioselective sensors, and asymmetric catalysts. In this study, we demonstrate the ratio of d-Cys and l-Cys playing an important role in determining the optical properties and the structures of self-assembled Cys-Au(I) supramolecules prepared through a simple reaction of tetrachloroaurate(III) with chiral cysteine (Cys). The irregularly shaped -[d-Cys-Au(I)] n- or - [l-Cys-Au(I)] n- supramolecules with a size larger than 500 nm possessing strong absorption in the near-UV region and chiroptical characteristics were only obtained from the reaction of Au(III) with d-Cys or l-Cys. On the other hand, spindle-shaped -[d/l-Cys-Au(I)] n- supramolecules were formed when using Au(III) with mixtures of d/l-Cys. Our results have suggested that Au(I)···Au(I) aurophilic interactions, and stacked hydrogen bonding and zwitterionic interactions between d/l-Cys ligands are important in determining their structures. The NaBH4-mediated reduction induces the formation of photoluminescent gold nanoclusters (Au NCs) embedded in the chiral -[d-Cys-Au(I)] n- or -[l-Cys-Au(I)] n- supramolecules with a quantum yield of ca. 10%. The as-formed Au NCs/-[d-Cys-Au(I)] n- and Au NCs/-[l-Cys-Au(I)] n- are an enantiospecific substrate that can trap l-carnitine and d-carnitine, respectively, and function as a nanomatrix for surface-assisted laser desorption/ionization mass spectrometry (LDI-MS). The high absorption efficiency of laser energy, analyte-binding capacity, and homogeneity of the Au NCs/-[Cys-Au(I)] n- allow for quantitation of enantiomeric carnitine down to the micromolar regime with high reproducibility. The superior efficiency of the Au NCs/-[d-Cys-Au(I)] n- substrate has been further validated by quantification of l-carnitine in dietary supplements with accuracy and precision. Our study has opened a new avenue for chiral quantitation of various analytes through LDI-MS using metal nanocomposites consisting of NCs and metal-ligand complexes.

Tumor suppressor p53 restrains cancer cell dissemination by modulating mitochondrial dynamics.

Tumor suppressor p53 plays a central role in preventing tumorigenesis. Here, we unravel how p53 modulates mitochondrial dynamics to restrain the metastatic properties of cancer cells. p53 inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling to attenuate the protein level of mitochondrial fission process 1 (MTFP1), which fosters the pro-fission dynamin-related protein 1 (Drp1) phosphorylation. This regulatory mechanism allows p53 to restrict cell migration and invasion governed by Drp1-mediated mitochondrial fission. Downregulating p53 expression or elevating the molecular signature of mitochondrial fission correlates with aggressive tumor phenotypes and poor prognosis in cancer patients. Upon p53 loss, exaggerated mitochondrial fragmentation stimulates the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling resulting in epithelial-to-mesenchymal transition (EMT)-like changes in cell morphology, accompanied by accelerated matrix metalloproteinase 9 (MMP9) expression and invasive cell migration. Notably, blocking the activation of mTORC1/MTFP1/Drp1/ERK1/2 axis completely abolishes the p53 deficiency-driven cellular morphological switch, MMP9 expression, and cancer cell dissemination. Our findings unveil a hitherto unrecognized mitochondria-dependent molecular mechanism underlying the metastatic phenotypes of p53-compromised cancers.

Synthesis and in situ sulfidation of molybdenum carbide MXene using fluorine-free etchant for electrocatalytic hydrogen evolution reactions.

Synthesizing MXenes from Mn+1AXn (MAX) phases using hazardous hydrogen fluoride is a common and effective method. However, fluorine termination on the basal planes and edges of the resulting MXenes is undesirable for the electrocatalytic hydrogen evolution reaction (HER), while oxygen (O), hydroxyl (OH), and sulfur (S) termination favors this reaction. Herein, we unveil a simple fluorine-free exfoliation and two-step vulcanization method for synthesizing molybdenum sulfide-modified molybdenum carbide (MoS2/Mo2CTx MXene, T = OH, O, S) for the HER in alkaline medium. Microwave-assisted hydrothermal treatment of the MAX phase (Mo3AlC2) with sodium hydroxide-sodium sulfide as an etching solution and thioacetamide as a source of sulfide ions enabled the selective dissolution of the aluminum (Al) layer and sulfidation of the surface Mo atoms to form amorphous MoS2. Thus, the vulcanization of Mo2CTx MXene resulted in the formation of MoS2/Mo2CTx MXene. The MoS2 formed on the surface of Mo2CTx provided enhanced stability by preventing oxidation. MoS2/Mo2CTx exhibited enhanced electrocatalytic activity toward the HER, mainly due to the O, OH, and amorphous MoS2 functionalities. The MoS2 sites on the surface exhibited an overpotential of 110 ± 7 mV at a current density of 10 mA cm-2 as a result of enhanced charge transfer and mass transfer. Thus, the sulfidation method demonstrated herein is capable of producing amorphous MoS2 structures on Mo2CTx MXene, which could be applied for the surface modification of other molybdenum-based nanomaterials or electrocatalysts to improve stability and enhance electrocatalytic activity.

Effective and enduring surgical treatment for targeted therapy-related paronychia: A retrospective study.

The development of targeted therapy has improved treatment outcomes for patients with non-small cell lung cancer (NSCLC). However, paronychia, a common adverse effect of targeted therapy, remains burdensome. Although conservative treatments for paronychia have been well reported in the literature, studies on the efficacy of surgical partial matricectomy for paronychia, are scarce. This study aimed to evaluate the effect of surgical partial matricectomy in targeted therapy-induced paronychia in patients with NSCLC. This retrospective cohort study included 11 patients with a total of 18 lesions on the big toes. Data on lung cancer stages, types and duration of targeted therapy, onset of paronychia, pain scale scores, conservative treatments, course of matricectomy, paronychia-free interval after matricectomy, and wound condition were collected from medical records. The Wilcoxon signed-rank test was used for analysis. The mean pain scale score after matricectomy was significantly lower than that after conservative treatments (1.00 ± 0.00 vs 2.94 ± 0.87; P < .001) and before treatment (1.00 ± 0.00 vs 3.06 ± 0.80; P < .001). The mean duration of matricectomy was significantly shorter than that of conservative treatments (3.22 ± 1.00 vs 56.56 ± 52.29 weeks; P < .001). Surgical partial matricectomy is an effective and enduring intervention for targeted therapy-related paronychia. It provides a shorter course of treatment, reduced pain, and improved appearance of the healed wound. Furthermore, surgical partial matricectomy could result in a better quality of life during targeted therapy than that of conservative treatments.

Comparison of Detection of Superior Gluteal Artery Perforator by Indocyanine Green Fluorescence Near-Infrared ANGIOGRAPHY and Handheld Acoustic Doppler Sonography for Reconstruction of Sacral Pressure Injury.

AIMS: Pressure injury is a gradually increasing disease in the aging society. The reconstruction of a pressure ulcer requires a patient and surgical technique. The patients were exposed to the radiation risk under other ways of detection of perforators such as computed tomographic angiography and magnetic resonance angiography. Here, we compared two radiation-free methods of a superior gluteal artery perforator (SGAP), flap harvesting and anchoring. One is the traditional method of detecting only handheld acoustic Doppler sonography (ADS) (Group 1). The other involves the assistance of intraoperative indocyanine green fluorescent near-infrared angiography (ICGFA) and handheld ADS (Group 2). MATERIALS AND METHODS: This is a single-center, retrospective, observational study that included patients with sacral pressure injury grades III and IV, who had undergone reconstructive surgery with an SGAP flap between January 2019 and January 2021. Two detection methods were used intraoperatively. The main outcome measures included the operative time, estimated blood loss, major perforator detection numbers, wound condition, and incidence of complications. RESULTS: Sixteen patients underwent an SGAP flap reconstruction. All patients were diagnosed with grade III to IV sacral pressure injury after a series of examinations. Group 1 included 8 patients with a mean operative time of 91 min, and the mean estimated blood loss was 50 mL. The mean number of perforators was 4. Postoperative complications included one wound infection in one case and wound edge dehiscence in one case. No mortality was associated with this procedure. The mean total hospital stay was 16 days. Group 2 included 8 patients with a mean operative time of 107.5 min, and the mean estimated blood loss was 50 mL. The mean number of perforators was 5. Postoperative complications included one wound infection. No mortality was associated with this procedure. The mean total hospital stay was 13 days. CONCLUSIONS: The combination of detection of the SGAP by ICGFA and handheld ADS for the reconstruction of a sacral pressure injury provides a more accurate method and provides the advantage of being radiation-free.

Simple and Efficient Pressure Ulcer Reconstruction via Primary Closure Combined with Closed-Incision Negative Pressure Wound Therapy (CiNPWT)-Experience of a Single Surgeon.

BACKGROUND: In this study, we aimed to analyze the clinical efficacy of closed-incision negative pressure wound therapy (CiNPWT) when combined with primary closure (PC) in a patient with pressure ulcers, based on one single surgeon's experience at our medical center. METHODS: We retrospectively reviewed the data of patients with stage III or IV pressure ulcers who underwent reconstruction surgery. Patient characteristics, including age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, application of CiNPWT to reconstructed wounds, duration of hospital stay, and wound complications were analyzed. RESULTS: Operation time (38.16 ± 14.02 vs. 84.73 ± 48.55 min) and duration of hospitalization (36.78 ± 26.92 vs. 56.70 ± 58.43 days) were shorter in the PC + CiNPWT group than in the traditional group. The frequency of debridement (2.13 ± 0.98 vs. 2.76 ± 2.20 times) was also lower in the PC + CiNPWT group than in the traditional group. The average reconstructed wound size did not significantly differ between the groups (63.47 ± 42.70 vs. 62.85 ± 49.94 cm2), and there were no significant differences in wound healing (81.25% vs. 75.38%), minor complications (18.75% vs. 21.54%), major complications (0% vs. 3.85%), or mortality (6.25% vs. 10.00%) between the groups. CONCLUSIONS: Our findings indicate that PC combined with CiNPWT represents an alternative reconstruction option for patients with pressure ulcers, especially in those for whom prolonged anesthesia is unsuitable.

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most crucial causes of chronic kidney disease (CKD). However, the efficacy and biomedical mechanisms of Chinese herbal medicine (CHM) for DKD in clinical settings remain unclear. OBJECTIVE: This study aimed to analyze the outcomes of DKD patients with CHM-only management and the possible molecular pathways of CHM by integrating web-based biomedical databases and real-world clinical data. METHODS: A total of 152,357 patients with incident DKD from 2004 to 2012 were identified from the National Health Insurance Research Database (NHIRD) in Taiwan. The risk of mortality was estimated with the Kaplan-Meier method and Cox regression considering demographic covariates. The inverse probability of treatment weighting was used for confounding bias between CHM users and nonusers. Furthermore, to decipher the CHM used for DKD, we analyzed all CHM prescriptions using the Chinese Herbal Medicine Network (CMN), which combined association rule mining and social network analysis for all CHM prescriptions. Further, web-based biomedical databases, including STITCH, STRING, BindingDB, TCMSP, TCM@Taiwan, and DisGeNET, were integrated with the CMN and commonly used Western medicine (WM) to explore the differences in possible target proteins and molecular pathways between CHM and WM. An application programming interface was used to assess these online databases to obtain the latest biomedical information. RESULTS: About 13.7% (20,947/131,410) of patients were classified as CHM users among eligible DKD patients. The median follow-up duration of all patients was 2.49 years. The cumulative mortality rate in the CHM cohort was significantly lower than that in the WM cohort (28% vs 48%, P<.001). The risk of mortality was 0.41 in the CHM cohort with covariate adjustment (99% CI 0.38-0.43; P<.001). A total of 173,525 CHM prescriptions were used to construct the CMN with 11 CHM clusters. CHM covered more DKD-related proteins and pathways than WM; nevertheless, WM aimed at managing DKD more specifically. From the overrepresentation tests carried out by the online website Reactome, the molecular pathways covered by the CHM clusters in the CMN and WM seemed distinctive but complementary. Complementary effects were also found among DKD patients with concurrent WM and CHM use. The risk of mortality for CHM users under renin-angiotensin-aldosterone system (RAAS) inhibition therapy was lower than that for CHM nonusers among DKD patients with hypertension (adjusted hazard ratio [aHR] 0.47, 99% CI 0.45-0.51; P<.001), chronic heart failure (aHR 0.43, 99% CI 0.37-0.51; P<.001), and ischemic heart disease (aHR 0.46, 99% CI 0.41-0.51; P<.001). CONCLUSIONS: CHM users among DKD patients seemed to have a lower risk of mortality, which may benefit from potentially synergistic renoprotection effects. The framework of integrating real-world clinical databases and web-based biomedical databases could help in exploring the roles of treatments for diseases.

Preservation of superior rectal artery in laparoscopically assisted subtotal colectomy with ileorectal anastomosis for slow transit constipation.

BACKGROUND: Slow transit constipation (STC) has traditionally been considered as a functional disorder. However, evidence is accumulating that suggests that most of the motility alterations in STC might be of a neuropathic etiology. If the patient does not meet the diagnosis of pelvic outlet obstruction and poorly response to conservative treatment, surgical intervention with subtotal colectomy may be effective. The most unwanted complication of the procedure is anastomotic leakage, however, preservation of the superior rectal artery (SRA) may reduce its incidence. AIM: To evaluate the preservation of the SRA in laparoscopically assisted subtotal colectomy with ileorectal anastomosis in STC patients. METHODS: This was a single-center retrospective observational study. STC was diagnosed after a series of examinations which included a colonic transit test, anal manometry, a balloon expulsion test, and a barium enema. Eligible patients underwent laparoscopically assisted total colectomy with ileorectal anastomosis and were examined between January 2016 and January 2018. The operation time, blood loss, time to first flatus, length of hospital days, and incidence of minor or major complications were recorded. RESULTS: A total of 32 patients (mean age, 42.6 years) who had received laparoscopic assisted subtotal colectomy with ileorectal artery anastomosis and preservation of the SRA. All patients were diagnosed with STC after a series of examinations. The mean operative time was 151 min and the mean blood loss was 119 mL. The mean day of first time to flatus was 3.0 d, and the mean hospital stay was 10.6 d. There were no any patients conversions to laparotomy. Post-operative minor complications including 1 wound infection and 1 case of ileus. There was no surgical mortality. No anastomosis leakage was noted in any of the patients. CONCLUSION: Laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the SRA can significantly improve bowel function with careful patient selection. Sparing the SRA may protect against anastomosis leakage.

Diagnosis and management of glandular papilloma of lung: A case report.

BACKGROUND: Solitary respiratory papilloma is a rare epithelial tumor that can be categorized into multiple subtypes depending on tumor location, histological presentation and number. The glandular type is the rarest, with only 30 cases available within the field. Hence, information on its identification and treatment is limited. In this report, we discuss the diagnostic strategy and management of glandular papilloma, along with a review of the literature. CASE SUMMARY: We describe a male 44-year-old nonsmoker who presented with a persistent cough and recurrent pneumonia, which he had experienced for over 2 years. A solitary pulmonary nodule with an endobronchial lesion was found via computed tomography of the chest. After a biopsy was obtained, no definite diagnosis could be made. Glandular papilloma of the lung was confirmed via video-assisted thoracoscopic anatomic resection of the right lower lobe of the lung. The patient remained disease-free after 6 mo follow up. CONCLUSION: Minimally invasive surgery is feasible for the surgical resection of endobronchial glandular papilloma. Although rare, glandular papilloma should be considered in patients with infection or endobronchial lesions.

Downregulation of miR-144 by triptolide enhanced p85α-PTEN complex formation causing S phase arrest of human nasopharyngeal carcinoma cells.

Selective pharmacologic targeting of cell cycle regulators is a potent anti-cancer therapeutic strategy. Here, we show that caspase-3-mediated p21 cleavage involves p53 independent of triptolide (TPL)-induced S phase arrest in human type 1 nasopharyngeal carcinoma (NPC) cells. Coimmunoprecipitation studies demonstrated that TPL causes S phase cell cycle arrest by suppressing the formation of cyclin A-phosphor (p)-cyclin-dependent kinas 2 (CDK2) (Thr 39) complexes. Ectopic expression of constitutively active protein kinase B1 (Akt1) blocks the induction of S phase arrest and the suppression of cyclin A expression and CDK2 Thr 39 phosphorylation by TPL. Expression of the phosphomimetic mutant CDK2 (T39E) rescues the cells from TPL-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TPL-triggered S phase arrest. Treatment with TPL induces an increase in the formation of complexes between unphosphorylated phosphatase and tensin homolog deleted from chromosome 10 (PTEN) and p85α in the plasma membrane. Decreased microRNA (miR)-144 expression and increased PTEN expression after TPL treatment were demonstrated, and TPL-enhanced p85α-PTEN complexes and inhibitory effects on Akt (Ser 473) phosphorylation and S phase arrest were suppressed by ectopic PTEN short hairpin RNA or miR-144 expression. Knockdown of endogenous miR-144 by miR-144 Trap upregulated PTEN expression and accordingly enhanced p85α-PTEN complex formation and S phase arrest. Collectively, the effect of TPL on S phase arrest in human NPC cells is likely to enhance the p85α-PTEN interaction in the plasma membrane by suppressing miR-144 expression, resulting in the attenuation of cyclin A-p-CDK2 (Thr 39) complex formation via Akt inactivation.

Mesoporous manganese oxide/manganese ferrite nanopopcorns with dual enzyme mimic activities: A cascade reaction for selective detection of ketoses.

Nanomaterials possessing enzyme-like activity have been extensively studied owing to their high stability and tunable catalytic properties. In this work, a simple method has been developed for the synthesis of porous manganese oxide/manganese ferrite (MnOx/MnFe2O4) nanopopcorns (MFNPs) in neutral media. The MFNPs exhibit dual enzymatic activities towards selective oxidation of ketoses followed by H2O2-induced decline of its catalytic activity. MFNPs, with MnFe2O4 as the core material and an outer layer rich in MnOx, were synthesized from ammonium iron(III) citrate and potassium permanganate at 70 °C for 12 h followed by annealing at 300 °C for 6 h. The nanozyme, MFNPs, exhibited oxidase-like activity, which was proved by the oxidation of amplex red (AR) in the presence of dissolved oxygen in the solution, to form fluorescent resorufin. The activity of MFNPs is highly suppressed by H2O2 as a result of its induced dissolution of MnOx. In addition, MFNPs having catalytic activity towards the selective oxidation of ketoses (e.g., fructose) followed by the formation of H2O2. The as-formed H2O2 diminished the catalytic activity of MFNPs for the AR oxidation to form fluorescent resorufin. Upon increasing fructose concentration, the fluorescence of resorufin decreases. Since the MFNPs do not show catalytic activity towards aldose sugars, such as glucose, sucrose, and mannose, the AR/MFNPs probe has high selectivity and sensitivity for detection of fructose with a limit of detection of 32 µM. Our study shows its great potential for quantitation of fructose in honey samples.

Arsenite-induced apoptosis can be attenuated via depletion of mTOR activity to restore autophagy.

Arsenic and its compounds are toxic environmental pollutants and known carcinogens. We investigated here the mechanism of arsenite-induced damage in renal cells. Treating human embryonic kidney cells (HEK293) with sodium arsenite reduces cell viability in a dose- and time-dependent manner. The decline of cell viability is due to apoptotic death since arsenite treatment reduces Akt activity and the Bcl2 level but increases caspase 3 activity and the cytochrome c level. These effects can be reverted by the addition of an apoptosis inhibitor. PTEN, the upstream negative regulator of Akt activity, was also reduced with arsenite treatment. Noticeably, PTEN markedly increased in the insoluble fraction of the cells, suggesting a cell failure in removing the damaged proteins. Arsenite treatment activates a variety of signaling factors. Among them, ERK and JNK are associated with autophagy via regulating the levels of LC3 and p62. With arsenite administration, the LC3 and p62 levels increased. However, lysosomal activity was decreased and led to the decline of autophagic activity. The addition of rapamycin, the mTOR inhibitor, activated the autophagic pathway that accelerated the removal of damaged proteins. The recovery of autophagy increased the viability of arsenite-treated cells. Similar to rapamycin treatment, the knockdown of mTOR expression also enhanced the viability of arsenite-treated cells. Both rapamycin treatment and mTOR knockdown enhanced ERK activity further, but reduced JNK activity and the p62 level in arsenite-treated cells. Lysosomal activity increased with the depletion of mTOR, indicating an increase of autophagic activity. These results reveal the critical role of mTOR in regulating the cell fate of arsenite-exposed renal cells.

Porous aluminum electrodes with 3D channels and zig-zag edges for efficient hydrogen evolution.

An eco-friendly electrochemical approach, including base and acid treatments, and anodization, has been developed for preparation of defect-rich porous aluminum electrodes for efficient hydrogen evolution. A small Tafel slope value of 43 mV dec-1 reveals improved reaction kinetics through the micropores, 3D channels, and zig-zag edges of the aluminum electrode. It exhibits an onset potential of 460 mV and an overpotential of 580 mV at the current density of 10 mA cm-2 due to the porous and edge structures that enhance the charge transfer and mass transport.

Self-assembled, bivalent aptamers on graphene oxide as an efficient anticoagulant.

Graphene oxide (GO) has unique structural properties, can effectively adsorb single-strand DNA through π-π stacking, hydrogen bonding and hydrophobic interactions, and is useful in many biotechnology applications. In this study, we developed a thrombin-binding-aptamers (15- and 29-mer) conjugated graphene oxide (TBA15/TBA29-GO) composite for the efficient inhibition of thrombin activity towards the formation of fibrin from fibrinogen. The TBA15/TBA29-GO composite was simply obtained by the self-assembly of TBA15/TBA29 hybrids on GO. The high density and appropriate orientation of TBA15/TBA29 on the GO surface enabled TBA15/TBA29-GO to acquire an ultrastrong binding affinity for thrombin (dissociation constant = 2.9 × 10-12 M). Compared to bivalent TBA15h20A20/TBA29h20A20 hybrids, the TBA15/TBA29-GO composite exhibited a superior anticoagulant potency (ca. 10-fold) against thrombin-mediated coagulation as a result of steric blocking effects and a higher binding affinity for thrombin. In addition, the prolonged thrombin clotting time, prothrombin time (PT), and activated partial thromboplastin time (aPTT) of TBA15/TBA29-GO were at least 2 times longer than those of commercially available drugs (heparin, argatroban, hirudin, and warfarin). The in vitro cytotoxicity and hemolysis analyses revealed the high biocompatibility of TBA15/TBA29-GO. The rat-tail bleeding assay of the hemostasis time and ex vivo PT and aPTT further revealed that TBA15/TBA29-GO is superior (>2-fold) to heparin, which is commonly used in the treatment and prevention of thrombotic diseases. Our multivalent, oligonucleotide-modified GO nanocomposites are easy to prepare, cost-effective, and highly biocompatible and they show great potential as effective anticoagulants for the treatment of thrombotic disorders.

Satellite-like Gold Nanocomposites for Targeted Mass Spectrometry Imaging of Tumor Tissues.

We have developed a simple, rapid, high-throughput cancer diagnosis system using functional nanoparticles (NPs) consisting of poly(catechin) capped-gold NPs (Au@PC NPs) and smaller nucleolin-binding aptamer (AS1411) conjugated gold NPs (AS1411-Au NPs). The AS1411-Au NPs/Au@PC NP is used as a targeting agent in laser desorption/ionization mass spectrometry (LDI-MS)-based tumor tissue imaging. Self-assembled core-shell Au@PC NPs are synthesized by a simple reaction of tetrachloroaurate(III) with catechin. Au@PC NPs with a well-defined and dense poly(catechin) shell (~40-60 nm) on the surface of each Au core (~60-80 nm) are obtained through careful control of the ratio of catechin to gold ions, as well as the pH of the reaction solution. Furthermore, we have shown that AS1411-conjugated Au NPs (13-nm) self-assembled on Au@PC NP can from a satellite-like gold nanocomposite. The high density of AS1411-Au NPs on the surface of Au@PC NP enhances multivalent binding with nucleolin molecules on tumor cell membranes. We have employed LDI-MS to detect AS1411-Au NPs/Au@PC NPs labeled nucleolin-overexpressing MCF-7 breast cancer cells through the monitoring of Au cluster ions ([Au n ]+; 1 ≤ n ≤ 3). The ultrahigh signal amplification from Au NPs through the formation of a huge number of [Au n ]+ ions results in a sensing platform with a limit of detection of 100 MCF-7 cells mL-1. Further, we have applied the satellite-like AS1411-Au NPs/Au@PC NP nanocomposite as a labeling agent for tumor tissue imaging by LDI-MS. Our nanocomposite-assisted LDI-MS imaging platform can be extended for simultaneous analysis of different tumor markers on cell membranes when using different ligand-modified metal nanoparticles.

Large-scale fabrication of a flexible, highly conductive composite paper based on molybdenum disulfide-Pt nanoparticle-single-walled carbon nanotubes for efficient hydrogen production.

Creating efficient hydrogen production properties from the macroscopic assembly of two-dimensional materials is still an unaccomplished goal. Here we report a facile route to fabricate a flexible MoS2/PtNPs/SWCNT paper with an ultralow onset potential of -35 mV, a Tafel slope of 39.6 mV per decade and over 60 h of electrochemical durability.

Ultrasound-mediated modulation of the emission of gold nanodots.

In this study, we employed ultrasound-based treatment to mediate the emission properties of (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide-capped gold nanodots (11-MUTAB-Au NDs). The as-prepared 11-MUTAB-Au NDs (sizes: ca. 1.8 nm), obtained from the reaction of gold nanoparticles (ca. 3 nm) and 11-MUTAB, exhibited very weak red photoluminescence (PL) near 670 nm [quantum yield (QY): 0.01%] upon excitation at 365 nm. After ultrasonication (20 W) for 2 h, however, the 11-MUTAB-Au NDs exhibited a >1000-fold enhancement in their PL intensity (QY: 11.5%), which shifted to a green color (ca. 540 nm) with a longer PL lifetime, due to the smaller size of the resulting NDs and the higher density of their capping 11-MUTAB ligands. Moreover, the PL of the 11-MUTAB-Au NDs returned to the near-infrared region (ca. 810 nm) after ultrasonication for a long period of time (>5 h). The dramatically different optical properties of these alkanethiol-protected Au NDs after ultrasonication were presumably due to variation in their ligand densities; these effects were highly regulated by varying the ultrasonication time and power. Because the size, oxidation state, surface ligand density, and PL of these Au NDs could be controlled simply through ultrasonic treatment, this approach might open up new avenues for the preparation of emission-tunable metallic (e.g., Au, Ag, Pt) NDs presenting various capping ligands.