A Visual Raman Nano-Delivery System Based on Thiophene Polymer for Microtumor Detection.

A visual Raman nano-delivery system (NS) is a widely used technique for the visualization and diagnosis of tumors and various biological processes. Thiophene-based organic polymers exhibit excellent biocompatibility, making them promising candidates for development as a visual Raman NS. However, materials based on thiophene face limitations due to their absorption spectra not matching with NIR (near-infrared) excitation light, which makes it difficult to achieve enhanced Raman properties and also introduces potential fluorescence interference. In this study, we introduce a donor-acceptor (D-A)-structured thiophene-based polymer, PBDB-T. Due to the D-A molecular modulation, PBDB-T exhibits a narrow bandgap of Eg = 2.63 eV and a red-shifted absorption spectrum, with the absorption edge extending into the NIR region. Upon optimal excitation with 785 nm light, it achieves ultra-strong pre-resonant Raman enhancement while avoiding fluorescence interference. As an intrinsically sensitive visual Raman NS for in vivo imaging, the PBDB-T NS enables the diagnosis of microtumor regions with dimensions of 0.5 mm × 0.9 mm, and also successfully diagnoses deeper tumor tissues, with an in vivo circulation half-life of 14.5 h. This research unveils the potential application of PBDB-T as a NIR excited visual Raman NS for microtumor diagnosis, introducing a new platform for the advancement of "Visualized Drug Delivery Systems". Moreover, the aforementioned platform enables the development of a more diverse range of targeted visual drug delivery methods, which can be tailored to specific regions.

Microwave ablation combined with percutaneous vertebroplasty for treating painful non-small cell lung cancer with spinal metastases under real-time temperature monitoring.

PURPOSE: To retrospectively study the therapeutic effect and safety performance of the combination strategies of the computed tomography (CT)-guided microwave ablation (MWA) and percutaneous vertebroplasty (PVP) as a treatment for painful non-small cell lung cancer (NSCLC) with spinal metastases. MATERIALS AND METHODS: A retrospective review included 71 patients with 109 vertebral metastases who underwent microwave ablation combined with percutaneous vertebroplasty by the image-guided and real-time temperature monitoring. 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. RESULTS: Technical success was achieved in all patients. The mean pre-procedure VAS score and morphine doses were 6.6 ± 1.8 (4-10) and 137.2 ± 38.7 (40-200) mg, respectively. The mean VAS scores and daily morphine doses at 24 h and 1, 4, 12, and 24 weeks postoperatively were 3.3 ± 1.9 and 73.5 ± 39.4 mg; 2.2 ± 1.5 and 40.2 ± 29.8 mg; 1.7 ± 1.2 and 31.3 ± 23.6 mg; 1.4 ± 1.1 and 27.3 ± 21.4 mg; and 1.3 ± 1.1 and 24.8 ± 21.0 mg, respectively (all P < 0.001). ODI scores significantly decreased (P < 0.05). Minor cement leakage occurred in 51 cases (46.8%), with one patient having a grade 3 neural injury. No local tumor progression was observed by follow-up imaging. CONCLUSIONS: MWA combined with PVP can significantly relieve pain and improve patients' quality of life, which implied this is an effective treatment option for painful NSCLC with spinal metastases. Additionally, its efficacy should be further verified through the mid- and long-term studies.

USP40 promotes hepatocellular carcinoma cell proliferation, migration and stemness by deubiquitinating and stabilizing Claudin1.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor that poses a major threat to people's lives and health. Previous studies have found that multiple deubiquitinating enzymes are involved in the pathogenesis of HCC. The purpose of this work was to elucidate the function and mechanism of the deubiquitinating enzyme USP40 in HCC progression. METHODS: The expression of USP40 in human HCC tissues and HCC cell lines was investigated using RT-qPCR, western blotting and immunohistochemistry (IHC). Both in vitro and in vivo experiments were conducted to determine the crucial role of USP40 in HCC progression. The interaction between USP40 and Claudin1 was identified by immunofluorescence, co-immunoprecipitation and ubiquitination assays. RESULTS: We discovered that USP40 is elevated in HCC tissues and predicts poor prognosis in HCC patients. USP40 knockdown inhibits HCC cell proliferation, migration and stemness, whereas USP40 overexpression shows the opposite impact. Furthermore, we confirmed that Claudin1 is a downstream gene of USP40. Mechanistically, USP40 interacts with Claudin1 and inhibits its polyubiquitination to stabilize Claudin1 protein. CONCLUSIONS: Our study reveals that USP40 enhances HCC malignant development by deubiquitinating and stabilizing Claudin1, suggesting that targeting USP40 may be a novel approach for HCC therapy.

Effect of repeated intravitreal anti-vascular endothelial growth factor drugs on corneal nerves.

To investigate the potential effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on corneal nerves. A total of 64 patients were treated with intravitreal injection of anti-VEGF drugs. There were 19 cases of neovascular age-related macular degeneration (AMD), 20 cases of diabetic macular edema (DME) and 25 cases of retinal vein occlusion (RVO). Twenty-nine cases were treated with aflibercept (2 mg/0.05 mL) whereas 35 cases were managed with ranibizumab (0.5 mg/0.05 mL). A corneal confocal microscope was used to collect images of corneal subbasal nerve plexus, and Image J was used for image analysis. The changes in corneal nerve were compared between 1 month after each injection and before injection. There were no significant differences in the density and length of corneal nerve at specific time after the surgery in comparison with baseline in patients who were given 3 intravitreal injections. There was no significant correlation between the numbers of injections and the changes of the corneal nerves. After 3rd injection, the nerve length of the DME group was markedly lower than that of AMD and RVO groups, the difference was statistically significant (P < .05). The nerve density of the DME group was not significantly different from that of AMD and RVO groups, whereas the nerve length and nerve density of the AMD and RVO groups were not statistically significant between each other also. The corneal nerve length after the 2nd and 3rd injections of Aflibercept were lower than that before surgery, the difference was statistically significant. There were no significant differences in nerve density and nerve length at each time point after Ranibizumab injection. The length and density of the corneal nerve after multiple injections in contralateral eye displayed no significant changes compared with the baseline. Repeated intravitreal anti-VEGF drug can reduce the length of corneal nerves. For patients who need repeated intravitreal injections of anti-VEGF drugs, especially in DM, attention should be paid on the changes affecting the corneal nerves. It is also needed to strengthen the local anti-inflammatory therapy to avoid infection and to use artificial tears to protect the microenvironment of the ocular surface after the surgery.

Significantly Longer Shedding of Norovirus Compared to Rotavirus and Adenovirus in Children with Acute Gastroenteritis.

Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus (p < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus (p < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children (p < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.

Development and validation of a nomogram to predict protein-energy wasting in patients with peritoneal dialysis: a multicenter cohort study.

Background: Protein-energy wasting (PEW) is a common complication in patients with peritoneal dialysis (PD). Few investigations involved risk factors identification and predictive model construction related to PEW. We aimed to develop a nomogram to predict PEW risk in patients with peritoneal dialysis. Methods: We collected data from end-stage renal disease (ESRD) patients who regularly underwent peritoneal dialysis between January 2011 and November 2022 at two hospitals retrospectively. The outcome of the nomogram was PEW. Multivariate logistic regression screened predictors and established a nomogram. We measured the predictive performance based on discrimination ability, calibration, and clinical utility. Evaluation indicators were receiver operating characteristic (ROC), calibrate curve, and decision curve analysis (DCA). The performance calculation of the internal validation cohort validated the nomogram. Results: In this study, 369 enrolled patients were divided into development (n = 210) and validation (n = 159) cohorts according to the proportion of 6:4. The incidence of PEW was 49.86%. Predictors were age, dialysis duration, glucose, C-reactive protein (CRP), creatinine clearance rate (Ccr), serum creatinine (Scr), serum calcium, and triglyceride (TG). These variables showed a good discriminate performance in development and validation cohorts (ROC = 0.769, 95% CI [0.705-0.832], ROC = 0.669, 95% CI [0.585-0.753]). This nomogram was adequately calibrated. The predicted probability was consistent with the observed outcome. Conclusion: This nomogram can predict the risk of PEW in patients with PD and provide valuable evidence for PEW prevention and decision-making.

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.

Hydrogen Promotes the Effectiveness of Bone Mesenchymal Stem Cell Transplantation in Rats with Spinal Cord Injury.

Although bone mesenchymal stem cell (BMSC) transplantation has been applied to the treatment of spinal cord injury (SCI), the effect is unsatisfactory due to the specific microenvironment (inflammation and oxidative stress) in the SCI area, which leads to the low survival rate of transplanted cells. Thus, additional strategies are required to improve the efficacy of transplanted cells in the treatment of SCI. Hydrogen possesses antioxidant and anti-inflammatory properties. However, whether hydrogen can enhance the effect of BMSC transplantation in the treatment of SCI has not yet been reported. This study was aimed at investigating whether hydrogen promotes the therapeutic effect of BMSC transplantation in the treatment of SCI in rats. In vitro, BMSCs were cultured in a normal medium and a hydrogen-rich medium to study the effect of hydrogen on the proliferation and migration of BMSCs. BMSCs were treated with a serum-deprived medium (SDM), and the effects of hydrogen on the apoptosis of BMSCs were studied. In vivo, BMSCs were injected into the rat model of SCI. Hydrogen-rich saline (5 ml/kg) and saline (5 ml/kg) were given once a day via intraperitoneal injection. Neurological function was evaluated using the Basso, Beattie, and Bresnahan (BBB) and CatWalk gait analyses. Histopathological analysis, oxidative stress, inflammatory factors (TNF-α, IL-1ß, and IL-6), and transplanted cell viability were detected at 3 and 28 days after SCI. Hydrogen can significantly enhance BMSC proliferation and migration and tolerance to SDM. Hydrogen and BMSC codelivery can significantly enhance neurological function recovery by improving the transplant cell survival rate and migration. Hydrogen can enhance the migration and proliferation capacity of BMSCs to repair SCI by reducing the inflammatory response and oxidative stress in the injured area. Hydrogen and BMSC codelivery is an effective method to improve BMSC transplantation in the treatment of SCI.

Performance and mechanism of sacrificed iron anode coupled with constructed wetlands (E-Fe) for simultaneous nitrogen and phosphorus removal.

Three anodic biofilm electrode coupled CWs (BECWs) with graphite (E-C), aluminum (E-Al), and iron (E-Fe), respectively, and a control system (CK) were constructed to evaluate the removal performance of N and P in the secondary effluent of wastewater treatment plants (WWTPs) under different hydraulic retention time (HRT), electrified time (ET), and current density (CD). Microbial communities, and different P speciation, were analyzed to reveal the potential removal pathways and mechanism of N and P in BECWs. Results showed that the optimal average TN and TP removal rates of CK (34.10% and 55.66%), E-C (66.77% and 71.33%), E-Al (63.46% and 84.93%), and E-Fe (74.93% and 91.22%) were obtained under the optimum conditions (HRT 10 h, ET 4 h, CD 0.13 mA/cm2), which demonstrated that the biofilm electrode could significantly improve N and P removal. Microbial community analysis showed that E-Fe owned the highest abundance of chemotrophic Fe(II) (Dechloromonas) and hydrogen autotrophic denitrifying bacteria (Hydrogenophaga). N was mainly removed by hydrogen and iron autotrophic denitrification in E-Fe. Moreover, the highest TP removal rate of E-Fe was attributed to the iron ion formed on the anode, causing co-precipitation of Fe(II) or Fe(III) with PO43--P. The Fe released from the anode acted as carriers for electron transport and accelerated the efficiency of biological and chemical reactions to enhance the simultaneous removal of N and P. Thus, BECWs provide a new perspective for the treatment of the secondary effluent from WWTPs.

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.

Comparative analysis of the efficacy of early and late surgical intervention for acute spinal cord injury: A systematic review and meta-analysis based on 16 studies.

BACKGROUND: Spinal cord injuries (SCI) are a devastating condition and can lead to severe functional and psychosocial problems. However, the influence of the timing of the surgical intervention for acute SCI remains debated, with substantial variability in clinical practice. Thus, this study aims to compare the efficacy of early and late surgical intervention for acute SCI. METHODS: A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to January 10, 2021 was conducted for relevant studies that compared early and late acute SCI. Neurological outcomes were assessed by American Spinal Injury Association (ASIA). Early surgery was defined as the surgical intervention within 24 h after spinal injury. The primary outcome was the change of ASIA score from baseline to follow-up time after spinal injury. Second primary outcomes were clinical outcomes including neurological improvement rate, mortality, length of stay (LOS), charges ($), complications and ASIA Impairment Scale (AIS). All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 16 studies including 3977 SCI patients were identified finally. Our pooled results indicated that, compared with late surgery, patients who underwent early surgery experienced more ASIA score improvement, with pooled MDs of 2.32 points (95% CI 1.07-3.57; P = 0.0003) in total motor scores, 5.13 points (95% CI 3.94-6.32; P < 0.0001) in light touch scores, and 4.49 points (95% CI 2.22-6.76; P = 0.0001) in pin prick scores respectively. In addition, patients receiving early surgery experienced more total motor score after surgery (MD 3.30; 95% CI 0.82-5.79; P = 0.009). Patients who had early surgery also had higher neurological improvement rate (OR 1.66; 95% CI 1.19-2.31; P = 0.003), shorter LOS (MD -4.77; 95% CI -7.42 to -2.12), less charges ($) (MD -0.33; 95% CI -0.43 to -0.22), lower incidence of complications (OR 0.62; 95% CI 0.48-0.81), and higher AIS improvement rate (OR 1.71; 95% CI 1.20-2.44) respectively. CONCLUSIONS: Compared with late surgery, acute SCI patients who underwent early surgery experienced greater recovery after spinal injury, with better neurological improvement, shorter LOS, less charges and lower incidence of complications.

The prevalence and levels of enteric viruses in groundwater of private wells in rural Alberta, Canada.

The prevalence and levels of enteric viruses in untreated groundwater of private wells used for drinking and/or agricultural practices in rural Alberta were studied using the qPCR panel assay, integrated cell culture with qPCR and cell culture in the volume of 500 liters per sample through serial sampling. Seven viruses were assessed including adenovirus, rotavirus, norovirus, astrovirus, sapovirus, reovirus and JC virus. Five viruses were detected with an overall positive detection rate of 6.33 % (45 of 711 samples). The most frequently detected virus was adenovirus (48.9%, 22/45) followed by rotavirus (44.4%, 20/45), reovirus (20%, 9/45), JC virus (6.7%, 3/45) and norovirus (6.7%, 3/45). There was no significant difference in the positive detection rates, ranging from 1.1% to 3.4% by various well settings used for broiler farms, cow/calf farms, feedlots and rural acreages. Effects of well characteristics (aquifer type, well depth, static level of water, well seal) and well completion lithology on potential viral contamination of groundwater of private wells were also analyzed upon available data. The findings demonstrate that occurrence of enteric viruses is low and viral contamination is sporadic in groundwater of private wells in rural Alberta. Conventional fecal bacterial indicators (coliform and/or E. coli) were not a representative marker for viral contamination in groundwater wells in rural Alberta.

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.

Demonstrating the reduction of enteric viruses by drinking water treatment during snowmelt episodes in urban areas.

This study investigates short-term fluctuations in virus concentrations in source water and their removal by full-scale drinking water treatment processes under different source water conditions. Transient peaks in raw water faecal contamination were identified using in situ online ß-d-glucuronidase activity monitoring at two urban drinking water treatment plants. During these peaks, sequential grab samples were collected at the source and throughout the treatment train to evaluate concentrations of rotavirus, adenovirus, norovirus, enterovirus, JC virus, reovirus, astrovirus and sapovirus by reverse transcription and real-time quantitative PCR. Virus infectivity was assessed through viral culture by measurement of cytopathic effect and integrated cell culture qPCR. Virus concentrations increased by approximately 0.5-log during two snowmelt/rainfall episodes and approximately 1.0-log following a planned wastewater discharge upstream of the drinking water intake and during a ß-d-glucuronidase activity peak in dry weather conditions. Increases in the removal of adenovirus and rotavirus by coagulation/flocculation processes were observed during peak virus concentrations in source water, suggesting that these processes do not operate under steady-state conditions but dynamic conditions in response to source water conditions. Rotavirus and enterovirus detected in raw and treated water samples were predominantly negative in viral culture. At one site, infectious adenoviruses were detected in raw water and water treated by a combination of ballasted clarification, ozonation, GAC filtration, and UV disinfection operated at a dose of 40 mJ cm-2. The proposed sampling strategy can inform the understanding of the dynamics associated with virus concentrations at drinking water treatment plants susceptible to de facto wastewater reuse.

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.

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.

Photodegradable CuS SERS Probes for Intraoperative Residual Tumor Detection, Ablation, and Self-Clearance.

Surface-enhanced Raman scattering (SERS) probes have exhibited great potential in biomedical applications. However, currently reported SERS probes are mainly fabricated by nondegradable Au or Ag nanostructures, which are not favorably cleared from the imaged tissues. This bottleneck hinders their in vivo applications. We herein explore a degradable SERS probe consisting of hollow CuS nanoparticles (NPs) to circumvent the current limitation. We identify, for the first time, the Raman enhancement effects of hollow CuS NPs as a SERS probe for Raman imaging of residual tumor lesions. Uniquely, CuS SERS probes are degradable, which stems from laser-induced photothermal effects of CuS NPs, leading to their disintegration from shell structures into individual crystals, thus facilitating their self-clearance from imaged tissues. This novel CuS SERS probe with photodegradation characteristics opens avenues for applying Raman imaging toward a myriad of biomedical 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.

Prevalence, levels and seasonal variations of human enteric viruses in six major rivers in Alberta, Canada.

The prevalence and seasonal variation of 7 viruses in 6 major rivers in Alberta were assessed using a combination of qPCR, cell culture and integrated cell culture with qPCR (ICC-qPCR). Water samples were collected monthly from rivers at different sites upstream and downstream of major urban centers. Seven viruses including rotavirus, adenovirus, astrovirus, norovirus, sapovirus, JC virus and enterovirus, were detected in at least one of the water samples at each site using qPCR. Rotavirus was most common with concentration ranging from 2.3 to 4.5 log10 genomic equivalent (GE) copies/L. Norovirus, sapovirus, astrovirus, adenoviruses and JC virus peaked during the winter (November to March). Viruses were most prevalent at the Bow River sampling site downstream of the City of Calgary, followed by the North Saskatchewan River site downstream of the City of Edmonton and the Red Deer River site downstream of the City of Red Deer. The detection rates and quantity of viruses had significant difference in the sampling sites between upstream and downstream of major urban centers (p < 0.001). 14% of the samples tested positive using viral culture indicating the presence of infectious viruses in river. Sequencing analysis identified human rotavirus in 75% of the samples collected from downstream versus 37% of the samples collected from upstream sites (p < 0.02). Multivariate binary regression showed that human activity in watersheds is a significant determinant of viruses in Alberta's Rivers. The discharge from wastewater treatment plants may be the possible sources of viral contamination. Seasonal coincidence of acute viral gastroenteritis outbreaks and monthly peak occurrence of enteric viruses in river water implies potential impact of waterborne viruses on human health.

UV inactivation of human infectious viruses at two full-scale wastewater treatment plants in Canada.

Ultraviolet (UV) disinfection is widely used to inactivate microorganisms prior to release of treated municipal wastewater. However, limited data are available for in situ inactivation of infectious enteric viruses by UV treatment at full-scale. In this study, a total of 51 pre-UV and 50 post-UV samples were collected over a two-year period from two wastewater treatment plants (WWTPs) and analyzed for noroviruses, rotavirus, reovirus, sapovirus, astrovirus, enteroviruses, adenoviruses and JC virus. Both pre-UV and post-UV samples had relatively high concentrations of these viruses determined by qPCR. Infectious viruses were also observed in 98% of pre-UV samples and 76% of post-UV samples by cell culture, using either cytopathic effect (CPE) or integrated cell culture with qPCR (ICC-qPCR). Reovirus was the most common virus detected by ICC-qPCR, present in 92% of pre-UV and 48% of post-UV samples. Infectious enterovirus and adenovirus were detected by ICC-qPCR in 33% and 31% of pre-UV samples, 14% and 20% of post-UV samples, respectively. Mean log10 reduction estimates for infectious reovirus was 1.2 and 1.8 log for the two WWTPs as assessed by ICC-qPCR, which was similar to the reduction of total infectious viruses (1.5 and 1.7 log) as assessed by CPE in cells culture. Overall, quantification of infectious reovirus appears to provide a useful index of enteric virus inactivation during wastewater treatment at full-scale. To our knowledge, this is the first comprehensive study to assess UV inactivation of human enteric viruses at full-scale in WWTPs using both molecular and cell culture techniques, providing important information for quantitative microbial risk assessment of UV inactivation of human viruses in municipal wastewater.