One-Dimensional MoS2 Nanoscrolls as Miniaturized Memories.

Dimensionality of materials is closely related to their physical properties. For two-dimensional (2D) semiconductors such as monolayer molybdenum disulfide (MoS2), converting them from 2D nanosheets to one-dimensional (1D) nanoscrolls could contribute to remarkable electronic and optoelectronic properties, yet the rolling-up process still lacks sufficient controllability, which limits the development of their device applications. Herein we report a modified solvent evaporation-induced rolling process that halts at intermediate states and achieve MoS2 nanoscrolls with high yield and decent axial uniformity. The accordingly fabricated nanoscroll memories exhibit an on/off ratio of ∼104 and a retention time exceeding 103 s and can realize multilevel storage with pulsed gate voltages. Such open-end, high-curvature, and hollow 1D nanostructures provide new possibilities to manipulate the hysteresis windows and, consequently, the charge storage characteristics of nanoscale field-effect transistors, thereby holding great promise for the development of miniaturized memories.

Toward 95.5% Efficient Red Emissive Carbon Dots: Oxidation State Enhancing Radiative Electron-Transition of Indole Fluorophore.

Red fluorescence carbon dots (CDs) are promising for diverse applications and have attracted tremendous research interest. However, it is still challenging to achieve red fluorescence CDs with high fluorescence quantum yields (QYs > 50%). Herein, three kinds of red fluorescence CDs with QYs of 53.48, 85.21, and 59.18% are prepared. Benefiting from the oxidation induced by atmospheric-pressure O2 plasma processing, 95.5% efficient red fluorescence emission is achieved. It is revealed that the indole based fluorophores act as the red-emitting photoluminescence center. The synergistic effect between the C-O-C structure and indole based fluorophores plays a key role in promoting the efficiency of radiative electron transition and controlling the red fluorescence QYs. Additionally, the CDs show promising prospects for in vivo bioimaging and low in vivo toxicity. This work shows a new way for achieving high-efficiency red fluorescence CDs, and it may guide the development of high-performance CDs for diverse applications.

Covalent Organic Framework-Structured Raman Probes for Ultrasensitive In Vivo Bioimaging.

Organic Raman probes, including polymers and small molecules, have attracted great attention in biomedical imaging owing to their excellent biocompatibility. However, the development of organic Raman probes is usually hindered by a mismatch between their absorption spectra and wavelength-fixed excitation, which makes it difficult to achieve resonance excitation necessary to obtain strong Raman signals. Herein, we introduce a covalent organic framework (COF) into the fine absorption spectrum regulation of organic Raman probes, resulting in their significant Raman signal enhancement. In representative examples, a polymer poly(diketopyrrolopyrrole-p-phenylenediamine) (DPP-PD) and a small molecule azobenzene are transformed into the corresponding COF-structured Raman probes. Their absorption peaks show an accurate match of less than 5 nm with the NIR excitation. As such, the COF-structured Raman probes acquire highly sensitive bioimaging capabilities compared to their precursors with negligible signals. By further mechanism studies, we discover that the crystallinity and size of COFs directly affect the π-conjugation degree of Raman probes, thus changing their bandgaps and absorption spectra. Our study offers a universal and flexible method for improving the signal performance of organic Raman probes without changing their structural units, making it more convenient to obtain the highly sensitive organic Raman probes for in vivo bioimaging.

GhMAC3e is involved in plant growth and defense response to Verticillium dahliae.

KEY MESSAGE: GhMAC3e expression was induced by various stresses and hormones. GhMAC3e may regulate plant growth by influencing auxin distribution, and play important roles in Verticillium wilt resistance via mediating SA signaling. The MOS4-Associated Complex (MAC) is a highly conserved protein complex involved in pre-mRNA splicing and spliceosome assembly, which plays a vital role in plant immunity. It comprises key components such as MOS4, CDC5, and PRL1. MAC3A/B, as U-box E3 ubiquitin ligases, are crucial for various plant processes including development, stress responses, and disease resistance. However, their roles in cotton remain largely unknown. In this study, we first cloned the GhMAC3e gene from cotton and explored its biological functions by using virus-induced gene silencing (VIGS) in cotton and transgenic overexpression in Arabidopsis. The results showed that GhMAC3e is ubiquitously expressed in cotton tissues and could be induced by salt stress, Verticillium dahliae (VD) infection, PEG, ABA, ETH, GA3, MeJA, and SA. Silencing GhMAC3e retarded primary stem growth and reduced biomass of cotton coupled with the reduced auxin content in the petioles and veins. Silencing GhMAC3e up-regulated expression of cell growth-related genes GhXTH16 and Gh3.6, while down-regulated GhSAUR12 expression. Ectopic expression of GhMAC3e in Arabidopsis significantly enhanced its resistance to Verticillium wilt (VW) in terms of decreased pathogen biomass and lowered plant mortality. Overexpression of GhMAC3e dramatically upregulated AtPR1 by around 15 fold and more than 262 fold under basal and VD inoculation condition, respectively. This change was not associated with the expression of GhNPR1. In conclusion, GhMAC3e may not only regulate plant growth by influencing auxin distribution and growth-related gene expression, but also play important roles in VW resistance via mediating SA signaling independent of NPR1 transcription level.

Microwave ablation combined with vertebral augmentation under real-time temperature monitoring for the treatment of painful spinal osteogenic metastases.

OBJECTIVE: To evaluate the safety and efficacy of computed tomography (CT)-guided microwave ablation combined with vertebral augmentation under real-time temperature monitoring in the treatment of painful osteogenic spinal metastases. METHODS: This retrospective study included 38 patients with 63 osteogenic metastatic spinal lesions treated using CT-guided microwave ablation and vertebral augmentation under real-time temperature monitoring. Visual analog scale scores, daily morphine consumption, and Oswestry Disability Index scores were used to evaluate efficacy of the treatment. RESULTS: Microwave ablation combined with vertebral augmentation reduced the mean visual analog scale scores from 6.40 ± 1.90 preoperatively to 3.32 ± 0.96 at 24 h, 2.24 ± 0.91 at 1 week, 1.92 ± 1.32 at 4 weeks, 1.79 ± 1.45 at 12 weeks, and 1.39 ± 1.12 at 24 weeks postoperatively (all p < 0.001). The mean preoperative daily morphine consumption was 108.95 ± 56.41 mg, which decreased to 50.13 ± 25.46 mg at 24 h, 31.18 ± 18.58 mg at 1 week, 22.50 ± 16.63 mg at 4 weeks, 21.71 ± 17.68 mg at 12 weeks, and 17.27 ± 16.82 mg at 24 weeks postoperatively (all p < 0.001). During the follow-up period, the Oswestry Disability Index scores significantly reduced (p < 0.001). Bone cement leakage occurred in 25 vertebral bodies, with an incidence of 39.7% (25/63). CONCLUSIONS: The results indicate that microwave ablation combined with vertebral augmentation under real-time temperature monitoring is a feasible, effective, and safe treatment for painful osteoblast spinal metastases.

Analysis of facial redness by comparing VISIA and YLGTD.

BACKGROUND: Erythema, characterized by redness of the skin, is a common symptom in various facial skin conditions. Recent advancements in image processing and analysis techniques have led to the development of methods for analyzing and assessing skin texture. This study aimed to investigate the correlation between the parameters of "You Look Good Today" (YLGTD) and VISIA in the detection and assessment of facial redness. MATERIALS AND METHODS: Thirty female subjects participated in this experiment, undergoing assessments using both YLGTD and VISIA. The subjects were evaluated for facial redness, and the feature count results within the red zone were measured by VISIA. YLGTD analyzed the number and percentage of red zone pixels. The assessments were conducted between [specific dates] in [location]. RESULTS: The results demonstrated a significant positive correlation between the feature count results within the red zone measured by VISIA and the number of red zone pixels. Similarly, YLGTD exhibited a significant positive correlation with the number and percentage of red zone pixels. CONCLUSION: In conclusion, our findings suggest a correlation between YLGTD and VISIA in the measurement of facial erythema. YLGTD can serve as a portable device for primary screening assessments, offering a convenient and reliable method to evaluate facial redness. This research contributes to the development of non-invasive techniques for assessing and monitoring facial skin conditions, providing valuable insights for dermatological diagnosis and cosmetic testing.

Molecular Planarization of Raman Probes to Avoid Background Interference for High-Precision Intraoperative Imaging of Tumor Micrometastases and Lymph Nodes.

The intraoperative imaging applications of a large number of Raman probes are hampered by the overlap of their signals with the background Raman signals generated by biological tissues. Here, we describe a molecular planarization strategy for adjusting the Raman shift of these Raman probes to avoid interference. Using this strategy, we modify the backbone of thiophene polymer-poly(3-hexylthiophene) (P3HT), and obtain the adjacent thiophene units planarized polycyclopenta[2,1-b;3,4-b']dithiophene (PCPDT). Compared with P3HT whose signal is disturbed by the Raman signal of lipids in tissues, PCPDT exhibits a 60 cm-1 blueshift in its characteristic signal. Therefore, the PCPDT probe successfully avoids the signal of lipids, and achieves intraoperative imaging of lymph nodes and tumor micrometastasis as small as 0.30 × 0.36 mm. In summary, our study presents a concise molecular planarization strategy for regulating the signal shift of Raman probes, and brings a tunable thiophene polymer probe for high-precision intraoperative Raman imaging.

An efficient method to enhance recovery and detection of SARS-CoV-2 RNA in wastewater.

Wastewater surveillance (WS) of SARS-CoV-2 currently requires multiple steps and suffers low recoveries and poor sensitivity. Here, we report an improved analytical method with high sensitivity and recovery to quantify SARS-CoV-2 RNA in wastewater. To improve the recovery, we concentrated SARS-CoV-2 viral particles and RNA from both the solid and aqueous phases of wastewater using an electronegative membrane (EM). The captured viral particles and RNA on the EM were incubated in our newly developed viral inactivation and RNA preservation (VIP) buffer. Subsequently, the RNA was concentrated on magnetic beads and inhibitors removed by washing. Without eluting, the RNA on the magnetic beads was directly detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Analysis of SARS-CoV-2 pseudovirus (SARS-CoV-2 RNA in a noninfectious viral coat) spiked to wastewater samples showed an improved recovery of 80%. Analysis of 120 wastewater samples collected twice weekly between May 2021 and February 2022 from two wastewater treatment plants showed 100% positive detection, which agreed with the results independently obtained by a provincial public health laboratory. The concentrations of SARS-CoV-2 RNA in these wastewater samples ranged from 2.4×102 to 2.9×106 copies per 100 mL of wastewater. Our method's capability of detecting trace and diverse concentrations of SARS-CoV-2 in complex wastewater samples is attributed to the enhanced recovery of SARS-CoV-2 RNA and efficient removal of PCR inhibitors. The improved method for the recovery and detection of viral RNA in wastewater is important for wastewater surveillance, complementing clinical diagnostic tests for public health protection.

Number of COVID-19 cases required in a population to detect SARS-CoV-2 RNA in wastewater in the province of Alberta, Canada: Sensitivity assessment.

With a unique and large size of testing results of 1,842 samples collected from 12 wastewater treatment plants (WWTP) for 14 months through from low to high prevalence of COVID-19, the sensitivity of RT-qPCR detection of SARS-CoV-2 RNA in wastewater that correspond to the communities was computed by using Probit analysis. This study determined the number of new COVID-19 cases per 100,000 population required to detect SARS-CoV-2 RNA in wastewater at defined probabilities and provided an evidence-based framework of wastewater-based epidemiology surveillance (WBE). Input data were positive and negative test results of SARS-CoV-2 RNA in wastewater samples and the corresponding new COVID-19 case rates per 100,000 population served by each WWTP. The analyses determined that RT-qPCR-based SARS-CoV-2 RNA detection threshold at 50%, 80% and 99% probability required a median of 8 (range: 4-19), 18 (9-43), and 38 (17-97) of new COVID-19 cases /100,000, respectively. Namely, the positive detection rate at 50%, 80% and 99% probability were 0.01%, 0.02%, and 0.04% averagely for new cases in the population. This study improves understanding of the performance of WBE SARS-CoV-2 RNA detection using the large datasets and prolonged study period. Estimated COVID-19 burden at a community level that would result in a positive detection of SARS-CoV-2 in wastewater is critical to support WBE application as a supplementary warning/monitoring system for COVID-19 prevention and control.

Tracking Emergence and Spread of SARS-CoV-2 Omicron Variant in Large and Small Communities by Wastewater Monitoring in Alberta, Canada.

Wastewater monitoring of SARS-CoV-2 enables early detection and monitoring of the COVID-19 disease burden in communities and can track specific variants of concern. We determined proportions of the Omicron and Delta variants across 30 municipalities covering >75% of the province of Alberta (population 4.5 million), Canada, during November 2021-January 2022. Larger cities Calgary and Edmonton exhibited more rapid emergence of Omicron than did smaller and more remote municipalities. Notable exceptions were Banff, a small international resort town, and Fort McMurray, a medium-sized northern community that has many workers who fly in and out regularly. The integrated wastewater signal revealed that the Omicron variant represented close to 100% of SARS-CoV-2 burden by late December, before the peak in newly diagnosed clinical cases throughout Alberta in mid-January. These findings demonstrate that wastewater monitoring offers early and reliable population-level results for establishing the extent and spread of SARS-CoV-2 variants.

Computed Tomography‒Guided Microwave Ablation Combined with Osteoplasty for the Treatment of Bone Metastases: A Multicenter Clinical Study.

PURPOSE: To evaluate the efficacy and safety of combined microwave ablation (MWA) and osteoplasty as a palliative therapy for painful bone metastases. MATERIALS AND METHODS: As an extension of a previous limited single-center study, a retrospective review was conducted for 147 patients (77 male, 70 female) with painful bone metastases who underwent MWA combined with osteoplasty. In total, 102 (69.4%), 41 (27.9%), and 4 (2.7%) patients had spinal metastases, extraspinal metastases, and both, respectively. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry disability index (ODI) scores before treatment and during the follow-up period (mean follow-up, 9.8 months; range 3-16). RESULTS: The mean VAS score significantly declined from 6.4 ± 2.3 before treatment to 3.2 ± 2.1, 1.9 ± 1.6, 1.8 ± 1.6, 1.8 ± 1.6, and 1.9 ± 1.6 at 24 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after treatment, respectively (P < .01). Furthermore, the mean daily morphine equivalent opioid consumption was significantly reduced from 81.5 ± 32.8 mg before treatment to 40.0 ± 20.6, 32.4 ± 10.2, 26.4 ± 10.0, 21.5 ± 8.3, and 19.3 ± 7.4 mg. The mean ODI score also declined after treatment (P < .0001). Major complications occurred in 4 of 147 patients, with 1 pathologic fracture, 1 nerve injury, and 2 mild skin infections. Minor cement leakages were observed at 69 sites (32.8%). CONCLUSIONS: MWA combined with osteoplasty is an effective and safe treatment for painful bone metastases.

Comparison of approaches to quantify SARS-CoV-2 in wastewater using RT-qPCR: Results and implications from a collaborative inter-laboratory study in Canada.

Detection of SARS-CoV-2 RNA in wastewater is a promising tool for informing public health decisions during the COVID-19 pandemic. However, approaches for its analysis by use of reverse transcription quantitative polymerase chain reaction (RT-qPCR) are still far from standardized globally. To characterize inter- and intra-laboratory variability among results when using various methods deployed across Canada, aliquots from a real wastewater sample were spiked with surrogates of SARS-CoV-2 (gamma-radiation inactivated SARS-CoV-2 and human coronavirus strain 229E [HCoV-229E]) at low and high levels then provided "blind" to eight laboratories. Concentration estimates reported by individual laboratories were consistently within a 1.0-log10 range for aliquots of the same spiked condition. All laboratories distinguished between low- and high-spikes for both surrogates. As expected, greater variability was observed in the results amongst laboratories than within individual laboratories, but SARS-CoV-2 RNA concentration estimates for each spiked condition remained mostly within 1.0-log10 ranges. The no-spike wastewater aliquots provided yielded non-detects or trace levels (<20 gene copies/mL) of SARS-CoV-2 RNA. Detections appear linked to methods that included or focused on the solids fraction of the wastewater matrix and might represent in-situ SARS-CoV-2 to the wastewater sample. HCoV-229E RNA was not detected in the no-spike aliquots. Overall, all methods yielded comparable results at the conditions tested. Partitioning behavior of SARS-CoV-2 and spiked surrogates in wastewater should be considered to evaluate method effectiveness. A consistent method and laboratory to explore wastewater SARS-CoV-2 temporal trends for a given system, with appropriate quality control protocols and documented in adequate detail should succeed.

Development of a highly efficient and specific L-theanine synthase.

γ-Glutamylcysteine synthetase (γ-GCS) from Escherichia coli, which catalyzes the formation of L-glutamylcysteine from L-glutamic acid and L-cysteine, was engineered into an L-theanine synthase using L-glutamic acid and ethylamine as substrates. A high-throughput screening method using a 96-well plate was developed to evaluate the L-theanine synthesis reaction. Both site-saturation mutagenesis and random mutagenesis were applied. After three rounds of directed evolution, 13B6, the best-performing mutant enzyme, exhibited 14.6- and 17.0-fold improvements in L-theanine production and catalytic efficiency for ethylamine, respectively, compared with the wild-type enzyme. In addition, the specific activity of 13B6 for the original substrate, L-cysteine, decreased to approximately 14.6% of that of the wild-type enzyme. Thus, the γ-GCS enzyme was successfully switched to a specific L-theanine synthase by directed evolution. Furthermore, an ATP-regeneration system was introduced based on polyphosphate kinases catalyzing the transfer of phosphates from polyphosphate to ADP, thus lowering the level of ATP consumption and the cost of L-theanine synthesis. The final L-theanine production by mutant 13B6 reached 30.4 ± 0.3 g/L in 2 h, with a conversion rate of 87.1%, which has great potential for industrial applications.

CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance.

Bypass signaling activation plays a crucial role in the acquired resistance of gefitinib, the first targeted drug in the clinic to treat advanced non-small cell lung cancer. Although the inactivation of bypass signaling by small-molecule inhibitors or monoclonal antibodies may overcome gefitinib resistance, their clinical use has been limited by the complex production process and off-target toxicity. Here we show CuS nanoparticles (NPs) behaved as a photodynamic nanoswitch to specifically abrogate overactive bypass signaling in resistant tumor cells without interfering with the same signal pathways in normal cells. In representative insulin growth factor-1 receptor (IGF1R) bypass activation-induced gefitinib resistant tumors, CuS NPs upon near-infrared laser irradiation locally elevated reactive oxygen species (ROS) level in tumor cells, leading to the blockage of bypass IGF1R and its downstream AKT/ERK/NF-κB signaling cascades. Consequently, laser-irradiated CuS NPs sensitized tumors to gefitinib treatment and prolonged the survival of mice with no obvious toxicity. Laser-irradiated CuS NPs may serve as a simple and safe nanomedicine strategy to overcome bypass activation-induced gefitinib resistance in a specific and controllable manner and provide insights into the treatment of a myriad of other resistant tumors in the field of cancer therapy.

Spiked Virus Level Needed To Correctly Assess Enteric Virus Recovery in Water Matrices.

Quantitative microbial risk assessment (QMRA) identifies human enteric viruses in municipal wastewater as the pathogen group requiring the highest log reductions for various reuse applications. However, the performance of methods for estimating virus concentration is not well understood, and without performance assessment, actual risks are likely severely underestimated. To evaluate the efficiency of virus recovery from water, a water sample is often spiked with "known" amounts of virus, and the virus is then recovered after a series of analytical procedures. Yet for water matrices such as wastewater, due to the unknown background concentrations of targeted viruses in the matrix and the variable recovery efficiency between individual processes, only an approximation of the recovery efficiency may be obtained from such spike-and-recovery experiments. In this study, we demonstrated theoretically that for two widely used approximations, the error in estimating virus recovery should be less than the ratio of the amount of target virus in the background sample to that in the spike. Furthermore, we developed an applicable method, based on this new understanding, for deciding on the amount of virus for spiking before conducting a spike-and-recovery experiment, so that the approximation error is restricted to an acceptable level for each individual process. Finally, we applied the method to a set of experimental data for viruses in wastewater, demonstrating its utility and noting its general applicability to other pathogens or water matrices.IMPORTANCE The performance of procedures for pathogen log reduction is at the heart of new risk-based guidance/regulation globally, yet the methods for undertaking assessments of pathogen recovery are not standardized despite their fundamental impacts on assessing log reductions. Here we describe the level of spiking agent(s) that is necessary to correctly assess spiked pathogen/surrogate recovery with whatever method is deployed. The significance of our research lies in identifying the importance of the amount of spiking agents for reducing uncertainty in recovery estimates, which will allow the development of a recommendation for spiking experiments, proactively applying this understanding.

Combination of Microwave Ablation and Percutaneous Osteoplasty for Treatment of Painful Extraspinal Bone Metastasis.

PURPOSE: To evaluate the efficacy and safety of microwave (MW) ablation combined with percutaneous osteoplasty (POP) on painful extraspinal bone metastases. MATERIALS AND METHODS: In this retrospective study, 50 adult patients with 56 extraspinal bone metastasis lesions, who suffered from refractory moderate to severe pain, were treated with MW ablation and POP. Changes in quality of life were evaluated based on the Visual Analog Scale (VAS), daily morphine consumption, and the Oswestry Disability Index (ODI) before and immediately after the procedure and during follow-up times. RESULTS: Technical success was achieved in all patients. Mean preoperative VAS score and morphine dose were 7.0 ± 2.6 (range, 3-10) and 66.7 ± 33.2 mg (range, 10-120 mg), respectively. Mean postoperative VAS scores and daily morphine doses were as follows: 1 day, 3.5 ± 2.1 and 36.1 ± 25.8 mg (P < .05); 1 week, 1.5 ± 1.7 and 12.2 ± 14.8 mg (P < .001); 1 month, 0.9 ± 1.4 and 5.7 ± 10.0 mg (P < .001); and 3 months, 0.6 ± 1.2 and 4.7 ± 8.4 mg (P < .001). A significant decrease in the ODI score was also observed (P < .05). Periprocedural death was not observed. A pathologic fracture occurred in 1 (2%) patient with femoral metastasis, and local infection was observed in 2 (4%) patients. Minor cement leakage occurred in 4 (8%) patients with no symptomatic or intra-articular extravasation. No local tumor progression occurred in patients with imaging follow-up. CONCLUSIONS: MW ablation combined with POP is an effective and safe treatment for painful extraspinal bone metastases, which can significantly relieve pain and improve quality of life.

Changes in norovirus genotype diversity in gastroenteritis outbreaks in Alberta, Canada: 2012-2018.

BACKGROUND: The emergence of norovirus genotype GII.4 variants has been associated with gastroenteritis pandemics worldwide, prompting molecular surveillance for early detection of novel strains. In this study, we aimed to analyze the outbreak activity of norovirus and characterize the norovirus strains circulating in Alberta between July 2012 and February 2018. METHODS: Stool samples from gastroenteritis outbreaks in Alberta were tested for norovirus at the Provincial Laboratory for Public Health using a multiplex real time-RT PCR assay. The ORF1 and ORF2-genotypes of norovirus positive samples were assigned based on phylogenetic analyses of partial polymerase and capsid sequences, respectively. RESULTS: A total of 530 norovirus outbreaks were identified. During July 2012 and June 2017 there was a gradual decrease in the annual number of GII.4 outbreaks, however, outbreak numbers increased from June 2017-February 2018. Four novel strains emerged: GII.17 Kawasaki in July 2014-June 2015, GII.P16/GII.4 Sydney in July 2015-June 2016, GII.P16/GII.2 and GII.P4 New Orleans/GII.4 Sydney in July 2016-June 2017. GII.Pe/GII.4 Sydney was the single predominant strain responsible for the majority (over 50%) of all norovirus outbreaks up to June 2015. Between June 2017 and February 2018, GII.P16/GII.4 Sydney was the leading strain causing 63% of all norovirus outbreaks. CONCLUSIONS: GII.4 stands as the predominant capsid genotype causing a large majority of the norovirus outbreaks in early 2018. An increase in genotype diversity was observed in the last years, characterized by a high circulation of non-GII.4 strains and GII.4 recombinants.

para-Aminothiophenol Radical Reaction-Functionalized Gold Nanoprobe for One-to-All Detection of Five Reactive Oxygen Species In Vivo.

Five major reactive oxygen species (ROS) are generated in diseases including H2O2, •OH, O2•-, ROO•, and 1O2. Simultaneous detection of the five ROS with a single probe is crucial for a comprehensive understanding of the development and progression of many diseases, such as cancer and inflammatory diseases. However, currently reported detection systems are limited by targeting one ROS with one probe. This one-to-one detection mode may fail to sufficiently unveil the diseased state. In this study, we achieved simultaneous detection of all the five ROS with one probe (i.e., one-to-all detection), by designing a novel para-aminothiophenol (PATP) and hemin-decorated gold (Au/PATP/Hemin) nanoprobe. The design is principled by our discovery that PATP can react with •OH, O2•-, ROO•, and 1O2 by a radical oxidative coupling mechanism to form 4,4'-dimercaptoazobenzene (DMAB). The DMAB then elicited strong characteristic surface-enhanced Raman scattering (SERS) peaks at 1142, 1386, and 1432 cm-1; which in turn enables direct detection of •OH, O2•-, ROO•, and 1O2 and indirect detection of H2O2 by hemin-catalyzed fenton reaction to convert H2O2 into •OH. In two representative ROS-elevated mice models of tumors and allergic dermatitis, the Au/PATP/Hemin nanoprobe demonstrated its robust performance of monitoring tumor development and inflammation progression in a highly sensitive and quantitative manner.

Up-Regulation Thioredoxin Inhibits Advanced Glycation End Products-Induced Neurodegeneration.

BACKGROUND/AIMS: Diabetic retinopathy (DR) is one of the most serious complications of diabetes and is the leading cause of adult blindness in developed countries. Advanced glycation end products (AGEs) accumulation in diabetes is associated with its complications. Thioredoxin (Trx) is a small molecule (12kDa) antioxidant protein widely distributed in mammalian tissues, which has important biological functions including anti-apoptosis and transcriptional regulation. In a previous study, we found that Trx plays a key role in retinal neurodegeneration prior to the occurrence of endothelial damage in diabetic mice. In this study, our aim is to determine the effect of Trx on neurodegeneration induced by AGEs in order to identify new therapeutic targets for the clinical treatment and prevention of DR. METHODS: In vivo, a high-fat diet and Streptozotocin (STZ) injection were used to generate a mouse model of diabetes. Histology was utilized to examine tissue morphology and measure the outer nuclear layer (ONL) thickness. Electroretinography (ERG) was used to assess retinal function and Western blot was used to examine protein expression. In vitro, three methods of Trx up-regulation were used, including a stable cell line that overexpresses Trx, treatment with Sulforaphane, and shRNA down-regulation Txnip. Cells were treated with AGEs, and level of apoptosis was performed to quantify this by flow cytometry and TUNEL. Quantitative Reverse Transcription PCR (qRT-PCR), Western blotting and immunofluorescence were used to measure gene and protein expression. Transmission electron microscopy (TEM) was used to observe autophagosomes. RESULTS: We found that diabetic mice display decreased retinal function and reduced ONL thickness with AGEs accumulation and a reduction of Trx expression. Up-regulation Trx can prevent the ONL thickness decrease in diabetic mice, as observed by H&E staining. In vitro, up-regulation Trx resulted in decreased intracellular ROS generation, reduced apoptosis by inhibited autophagy. CONCLUSION: Up-regulating Trx inhibited neurodegeneration induced by AGEs. The underlying mechanism may be related to inhibit Txnip/mTOR pathway-mediated autophagy.

Hyperspectral Imaging Detection of Total Viable Count from Vacuum Packing Cooling Mutton Based on GA and CARS Algorithms.

In the process of spectral modeling, spectral extraction of characteristic bands with different variable screening algorithms is an important step for improving the model effects. Total viable count of cooling mutton under vacuum packing condition was chosen as the research index in this paper, while the influence of 2 variable screening algorithms on its hyperspectral PLS model effects was compared. Mutton muscle spectra of Regions of interest (ROIs) were extracted and preprocessed. Subsequently, Genetic Algorithm (GA) and Competitive Adaptive Reweighted Sampling (CARS) were applied to extract characteristic bands from preprocessed spectra at full band range of 473～1 000 nm. Model effects of GA-PLS, CARS-PLS and W-PLS with corresponding bands selection were contrasted and analyzed. The results indicated that both model effects of GA-PLS, CARS-PLS were better than that of W-PLS, and CARS-PLS model effect was optimal. As for the CARS-PLS model, the determination coefficient (R2c) and root mean square error (RMSEC) of calibration set was 0.96 and 0.29, and the determination coefficient (R2cv) and root mean square error (RMSECV) of leave-one-out cross validation was 0.92 and 0.46, respectively. Meanwhile, the determination coefficient (R2p), root mean square error of prediction (RMSEP) and the ratio of standard deviation to standard error of prediction (RPD) of prediction set was 0.92 and 0.47 and 3.58, respectively. Therefore, hyperspectral imaging (HSI) technology combined with CARS-PLS can achieve quick, non-destructive and accurate detection of mutton total viable count.