ATP promotes protein coacervation through conformational compaction.

ATP has been recognized as a hydrotrope in the phase separation process of intrinsically disordered proteins (IDPs). Surprisingly, when using the disordered RG/RGG-rich motif from HNRNPG protein as a model system, we discover a biphasic relationship between the ATP concentration and IDP phase separation. We show that at a relatively low ATP concentration, ATP dynamically interacts with the IDP, which neutralizes protein surface charges, promotes intermolecular interactions, and consequently promotes phase separation. We further demonstrate that ATP induces a compact conformation of the IDP, accounting for the reduced solvent exchange rate and lower compression ratio during phase separation. As ATP concentration increases, its hydrotropic properties emerge, leading to the dissolution of the phase-separated droplets. Our finding uncovers a complex mechanism by which ATP molecules modulate the structure, interaction, and phase separation of IDPs, and accounts for the distinct phase separation behaviors for the charge-rich RGG motif and other low-complexity IDPs.

Highly Multiplexing, Throughput and Efficient Single-Cell Protein Analysis with Digital Microfluidics.

Proteins as crucial components of cells are responsible for the majority of cellular processes. Sensitive and efficient protein detection enables a more accurate and comprehensive investigation of cellular phenotypes and life activities. Here, a protein sequencing method with high multiplexing, high throughput, high cell utilization, and integration based on digital microfluidics (DMF-Protein-seq) is proposed, which transforms protein information into DNA sequencing readout via DNA-tagged antibodies and labels single cells with unique cell barcodes. In a 184-electrode DMF-Protein-seq system, ≈1800 cells are simultaneously detected per experimental run. The digital microfluidics device harnessing low-adsorbed hydrophobic surface and contaminants-isolated reaction space supports high cell utilization (>90%) and high mapping reads (>90%) with the input cells ranging from 140 to 2000. This system leverages split&pool strategy on the DMF chip for the first time to overcome DMF platform restriction in cell analysis throughput and replace the traditionally tedious bench-top combinatorial barcoding. With the benefits of high efficiency and sensitivity in protein analysis, the system offers great potential for cell classification and drug monitoring based on protein expression at the single-cell level.

Study on the Tip Leakage Loss Mechanism of a Compressor Cascade Using the Enhanced Delay Detached Eddy Simulation Method.

The leakage flow has a significant impact on the aerodynamic losses and efficiency of the compressor. This paper investigates the loss mechanism in the tip region based on a high-load cantilevered stator cascade. Firstly, a high-fidelity flow field structure was obtained based on the Enhanced Delay Detached Eddy Simulation (EDDES) method. Subsequently, the Liutex method was employed to study the vortex structures in the tip region. The results indicate the presence of a tip leakage vortex (TLV), passage vortex (PV), and induced vortex (IV) in the tip region. At i=4°,8°, the induced vortex interacts with the PV and low-energy fluid, forming a "three-shape" mixed vortex. Finally, a qualitative and quantitative analysis of the loss sources in the tip flow field was conducted based on the entropy generation rate, and the impact of the incidence on the losses was explored. The loss sources in the tip flow field included endwall loss, blade profile loss, wake loss, and secondary flow loss. At i=0°, the loss primarily originated from the endwall and blade profile, accounting for 40% and 39%, respectively. As the incidence increased, the absolute value of losses increased, and the proportion of loss caused by secondary flow significantly increased. At i=8°, the proportion of secondary flow loss reached 47%, indicating the most significant impact.

Digital microfluidics for biological analysis and applications.

Digital microfluidics (DMF) is an emerging liquid-handling technology based on arrays of microelectrodes for the precise manipulation of discrete droplets. DMF offers the benefits of automation, addressability, integration and dynamic configuration ability, and provides enclosed picoliter-to-microliter reaction space, making it suitable for lab-on-a-chip biological analysis and applications that require high integration and intricate processes. A review of DMF bioassays with a special emphasis on those actuated by electrowetting on dielectric (EWOD) force is presented here. Firstly, a brief introduction is presented on both the theory of EWOD actuation and the types of droplet motion. Subsequently, a comprehensive overview of DMF-based biological analysis and applications, including nucleic acid, protein, immunoreaction and cell assays, is provided. Finally, a discussion on the strengths, challenges, and potential applications and perspectives in this field is presented.

Survival and risk factors among upper tract urothelial carcinoma patients after radical nephroureterectomy in Northeast China.

Objective: The study objective was to investigate the prognostic risk factors related to overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Patients were then divided into different risk groups (based on their number of prognostic risk factors), and specific postoperative treatment plans were formulated for patients in different risk groups. Methods: We retrospectively analyzed the data of 401 patients with UTUC who underwent RNU between 2010 and 2020. Univariate and multivariate Cox regression analyses were used to evaluate the associations of clinicopathological variables with prognosis among UTUC patients. Kaplan-Meier survival analysis of patients in different risk groups (based on their number of prognostic risk factors) was conducted. Results: Multivariate Cox regression analysis showed that sex (being male), LVI, pT stage (>pT2), and lack of postoperative intravesical instillation were independent risk predictors of shorter OS, CSS, RFS, and MFS (all P<0.05). Laparoscopic RNU was also associated with shorter OS, CSS, and MFS, but not with shorter RFS (P=0.068). After risk stratification, the 5-year OS, CSS, RFS, and MFS in the high-risk group were 42.3%, 46.4%, 41%, and 46%, respectively. Conclusions: Sex (being male), LVI, pT stage (>pT2), and intravesical instillation were independent predictors of OS, CSS, RFS, and MFS for UTUC. All were risk factors, except for intravesical instillation, which was a protective factor. Additionally, laparoscopic RNU was an independent risk factor for OS, CSS, and MFS. Patients in the high-risk group may benefit greatly from adjuvant or neoadjuvant chemotherapy.

Dose of intra-operative opioids has no impact on recurrence or survival in primary liver cancer.

BACKGROUND: Intra-operative use of opioid analgesics might have an impact on cancer recurrence and survival after surgery. The objective of this study was to investigate the association between the intra-operative fentanyl equivalents and survival outcomes in patients with primary liver cancer after receiving hepatectomy. METHODS: This was a retrospective single-center cohort study, and clinical data of 700 patients with primary liver cancer who underwent hepatectomy in Harbin Medical University Cancer Hospital from September 2013 to August 2018 were reviewed. After propensity matching, 376 patients were included. Patients were divided into high-dose and low-dose groups according to the median intra-operative fentanyl equivalents (1.500 mg). Kaplan Meier curve and Cox proportional hazards regression model were used. RESULTS: Results of univariable analysis showed there were no significant differences in recurrence-free survival (RFS) (p = 0.136) and overall survival (OS) (p = 0.444) between high-dose fentanyl equivalents and low-dose fentanyl equivalents group. The multivariable Cox regression analysis found that the dose of intra-operative fentanyl equivalents was not associated with RFS (HR: 1.119, 95%CI: 0.851-1.472, p = 0.422) or OS (HR: 0.939, 95%CI: 0.668-1.319, p = 0.715). CONCLUSIONS: The amounts of intra-operative fentanyl equivalents had no impact on recurrence-free or overall survival in patients with primary liver cancer after curative hepatectomy.

Bone pain from spinal metastases: Iodine-125 brachytherapy.

OBJECTIVES: This study evaluated the analgesic efficacy and safety of CT-guided iodine-125 (125I) brachytherapy in patients with spinal metastasis-induced pain who were not suitable to receive radiotherapy. METHODS: A cohort of 68 patients with spinal metastasis induced pain not fully relieved by opioids and did not receive external beam radiation therapy due to poor general status were enrolled and underwent CT-guided 125I brachytherapy for analgesic treatment. RESULTS: Patients were followed for 8 weeks after brachytherapy. Mean Numerical Rating Scale score before brachytherapy was 7.3±1.3 and decreased to 3.3±0.9, 2.6±0.8, 2.7±0.8, 2.9±0.9 and 3.3±1.1 at weeks 1, 2, 4, 6 and 8, respectively, after brachytherapy. Daily dose of morphine equivalent was 105.1±28.0 mg before brachytherapy and decreased to 45.3±13.7, 39.9±14.2, 40.4±14.9, 48.5±18.0 and 62.4±17.5 mg at weeks 1, 2, 4, 6 and 8, respectively, after brachytherapy. Patients had fewer daily episodes of breakthrough pain after brachytherapy (p<0.001). Patients had improvement in pain-related functional interference and in hospital anxiety and depression score after brachytherapy. CONCLUSIONS: CT-guided 125I brachytherapy is an effective and safe intervention for patients with spinal metastasis-induced pain who are not able to receive radiation therapy.

Pt/(InGa)2O3/n-Si Heterojunction-Based Solar-Blind Ultraviolet Photovoltaic Detectors with an Ideal Absorption Cutoff Edge of 280 nm.

Ga2O3 is a popular material for research on solar-blind ultraviolet detectors. However, its absorption cutoff edge is 253 nm, which is not an ideal cutoff edge of 280 nm. In this work, by adjusting the ratio of In/Ga elements in the films, a high-quality (In0.11Ga0.89)2O3 film with an absorption cutoff edge of 280 nm was obtained, which owns a uniform surface and preferred orientation. On this basis, a solar-blind ultraviolet photovoltaic detector was constructed based on the Pt/(In0.11Ga0.89)2O3/n-Si heterojunction. When the device is exposed to 254 nm UV light, its open-circuit voltage (VOC) can reach 354 mV. Under 0 V bias, the device has a responsivity of 0.48 mA/W with a rise time of 0.47 s and a decay time of 0.37 s; under -7 V bias, the device achieves a responsivity of 16.96 mA/W with a rise time of 0.17 s and a decay time of 0.33 s. The spectral response characteristics of the device show that it has a selective response to solar-blind ultraviolet light (cutoff wavelength is 280 nm) with a rejection ratio (R254 nm/R310 nm), which is greater by more than two orders of magnitude. This work provides a good reference for adjusting the band gap of Ga2O3-based films and broadening their application fields.

Gabapentin enhances the antinociceptive effect of intrathecal morphine in refractory cancer pain patients.

PURPOSE: Morphine infusion through Intrathecal Drug Delivery System (IDDS) is widely used to relieve refractory cancer pain. However, continuous escalation of morphine dose caused by opioid tolerance and/or progress of cancer was commonly observed. Combining morphine with medications of different analgesic mechanisms is applied to blunt the rate of morphine increase. The purpose of this study was to determine the analgesic efficacy and safety of combining gabapentin with morphine after IDDS implantation. METHODS: This study compared patients that received IDDS implantation from January 1, 2017 to November 10, 2018 in our institute. Key outcomes included change in mean pain score, dose of morphine used in patients, percentage of patients with 30% and 50% reduction in mean pain score, Patient Global Impression of Change scores, breakthrough pain characters and side effects. RESULTS: 34 patients in the combination group (morphine + gabapentin) and 40 patients in the monotherapy group(morphine)were analyzed. The results showed that both therapy groups achieved similar analgesic efficacy, demonstrated by Numerical rating scale (2.42 ± 0.88 vs 2.57 ± 0.85; Combination vs Monotherapy), PGIC and responder status. Mean daily dose of morphine was significantly lower in combination group compared to monotherapy group (3.54 ± 1.29 mg vs 4.64 ± 1.28 mg, P = 0.007). More patients experienced dizziness and somnolence after receiving combination therapy compared to morphine-alone treatment although no statistical significance was found (P = 0.49). CONCLUSION: Addition of gabapentin achieved similar analgesic efficacy with lower dose of morphine compared to morphine alone accompanying with higher incidence of dizziness and somnolence.

[Repair of electric burn wound in the upper limbs with lateral intercostal perforator-based pedicled flap].

OBJECTIVE: To describe an operative method for the repair of electric burn wound in the upper limbs with lateral intercostal perforator-based pedicled flap, and to observe its clinical effect. METHODS: Intercostal artery perforator-based pedicled abdominal flap with the blood supply originating from the lateral perforator branches of the 7th-10th intercostal arteries were used to repair the wounds of 6 patients with burn wounds in elbows, forearm, wrists and palms. The pedicles were (16. 0 cm x 12. 0 cm) - (9. 0 cm x 7.0 cm) in area, and the pedicles were severed 18 to 21 days after the operation. The survival and the appearance of the flaps were observed after operation. RESULTS: The procedure was easy and safe, and there was reliable and adequate blood supply in the lateral intercostal perforator-based pedicled flap. All the flaps survived in 5 patients, except marginal necrosis (3.5 cm x 2. 0 cm) was found in the distal portion of flap because flap cutting exceeded the paraumbilical line. The appearance was satisfactory after operation. CONCLUSION: This flap is suitable for the repair of deep wounds in hands, forearms, and elbows.