Integrated Manipulation and Addressing of Spin Defect in Diamond.

Scalable and addressable integrated manipulation of qubits is crucial for practical quantum information applications. Different waveguides have been used to transport the optical and electrical driving pulses, which are usually required for qubit manipulation. However, the separated multifields may limit the compactness and efficiency of manipulation and introduce unwanted perturbation. Here, we develop a tapered fiber-nanowire-electrode hybrid structure to realize integrated optical and microwave manipulation of solid-state spins at nanoscale. Visible light and microwave driving pulses are simultaneously transported and concentrated along an Ag nanowire. Studied with spin defects in diamond, the results show that the different driving fields are aligned with high accuracy. The spatially selective spin manipulation is realized. And the frequency-scanning optically detected magnetic resonance (ODMR) of spin qubits is measured, illustrating the potential for portable quantum sensing. Our work provides a new scheme for developing compact, miniaturized quantum sensors and quantum information processing devices.

Development of machine learning models to predict perioperative blood transfusion in hip surgery.

BACKGROUND: Allogeneic Blood transfusion is common in hip surgery but is associated with increased morbidity. Accurate prediction of transfusion risk is necessary for minimizing blood product waste and preoperative decision-making. The study aimed to develop machine learning models for predicting perioperative blood transfusion in hip surgery and identify significant risk factors. METHODS: Data of patients undergoing hip surgery between January 2013 and October 2021 in the Peking Union Medical College Hospital were collected to train and test predictive models. The primary outcome was perioperative red blood cell (RBC) transfusion within 72 h of surgery. Fourteen machine learning algorithms were established to predict blood transfusion risk incorporating patient demographic characteristics, preoperative laboratory tests, and surgical information. Discrimination, calibration, and decision curve analysis were used to evaluate machine learning models. SHapley Additive exPlanations (SHAP) was performed to interpret models. RESULTS: In this study, 2431 hip surgeries were included. The Ridge Classifier performed the best with an AUC = 0.85 (95% CI, 0.81 to 0.88) and a Brier score = 0.21. Patient-related risk factors included lower preoperative hemoglobin, American Society of Anesthesiologists (ASA) Physical Status > 2, anemia, lower preoperative fibrinogen, and lower preoperative albumin. Surgery-related risk factors included longer operation time, total hip arthroplasty, and autotransfusion. CONCLUSIONS: The machine learning model developed in this study achieved high predictive performance using available variables for perioperative blood transfusion in hip surgery. The predictors identified could be helpful for risk stratification, preoperative optimization, and outcomes improvement.

Cell-based shear stress sensor for bioprocessing.

Shear stress during bioreactor cultivation has significant impact on cell health, growth, and fate. Mammalian cells, such as T cells and stem cells, in next-generation cell therapies are especially more sensitive to shear stress present in their culture environment than bacteria. Therefore, a base knowledge about the shear stress imposed by the bioprocesses is needed to optimize the process parameters and enhance cell growth and yield. However, typical computational flow dynamics modeling or PCR-based assays have several limitations. Implementing and interpreting computational modeling often requires technical specialties and also relies on many simplifications in modeling. PCR-based assays evaluating changes in gene expression involve cumbersome sample preparation with the use of advanced lab equipment and technicians, hampering rapid and straightforward assessment of shear stress. Here, we developed a simple, cell-based shear stress sensor for measuring shear stress levels in different bioreactor types and operating conditions. We engineered a CHO-DG44 cell line to make its stress sensitive promoter EGR-1 control GFP expression. Subsequently, the stressed CHO cells were transferred into a 96 well plate, and their GFP levels (population mean fluorescence) were monitored using a cell analysis instrument (Incucyte®, Sartorius Stedim Biotech) over 24 hours. After conducting sensor characterization, which included chemical induced stress and fluid shear stress, and stability investigation, we tested the shear stress sensor in the Ambr® 250 bioreactor vessels (Sartorius Stedim Biotech) with different impeller and vessel designs. The results showed that the CHO cell-based shear stress sensors expressed higher GFP levels in response to higher shear stress magnitude or exposure time. These sensors are useful tools to assess shear stress imposed by bioreactor conditions and can facilitate the design of various bioreactor vessels with a low shear stress profile.

Association between preoperative autonomic nervous system function and post-induction hypotension in elderly patients: a protocol for a cohort study.

INTRODUCTION: Post-induction hypotension (PIH), which is prevalent among elderly patients, is associated with adverse perioperative outcomes. As a critical part of blood pressure regulation, baroreflex control is believed to be closely related to intraoperative blood pressure fluctuations. Spontaneous baroreflex sensitivity and heart rate variability measurement can aid evaluation of patients' autonomic function. This study aims to determine the association between preoperative decreased baroreflex function and PIH in elderly patients. METHODS AND ANALYSIS: This prospective cohort study will enrol patients who are 65 years old and above, scheduled for elective non-cardiac surgery under general anaesthesia, and American Society of Anesthesiologists physical status I-III (n=180). Baseline assessment will include routine preoperative evaluations as well as symptoms and anamneses associated with baroreflex failure. Preoperative autonomic function monitoring will be performed through 20 min of continuous beat-to-beat heart rate and blood pressure monitoring using LiDCO rapid (Masimo Corporation, USA). The primary outcome will be PIH. Detailed use of anaesthetic agents during induction and maintenance will be documented for adjustment in multivariable analyses. ETHICS AND DISSEMINATION: The Research Ethics Committee of Peking Union Medical College Hospital approved the study protocol (I-22PJ008). We aim to publish and disseminate our findings in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05425147.

Wastewater inputs reduce the CO2 uptake by coastal oceans.

Every year a large quantity of wastewater is generated worldwide, but its influence on the carbon dioxide (CO2) uptake by coastal oceans is not well understood. Here, sea surface CO2 partial pressure (pCO2) and air-sea CO2 flux were examined in the Jiaozhou Bay (JZB), a temperate coastal bay strongly disturbed by wastewater inputs. Monthly surveys from April 2014 through March 2015 showed that surface pCO2 in the JZB substantially varied both temporally and spatially between 163 µatm and 1222 µatm, with an annual average of 573 µatm. During April-December, surface pCO2 was oversaturated with respect to the atmosphere, with high values exceeding 1000 µatm in the northeastern part of the bay, where seawater salinity was low mainly due to the inputs of wastewater with salinity close to zero. During January-March, surface pCO2 was undersaturated, with the lowest value of <200 µatm also mainly in the northeastern part because of low water temperature and strong biological production. Over an annual cycle, apparently sea surface temperature dominated the monthly variation of surface pCO2 in this shallow bay, while wastewater inputs and related biological production/respiration dominated its spatial variability. Overall, the JZB was a net CO2 source to the atmosphere, emitting 9.6 ± 10.8 mmol C m-2 d-1, unlike its adjacent western part of the Yellow Sea and most of the temperate coastal oceans which are a net CO2 sink. This was possibly associated with wastewater inputs that cause high sea surface pCO2 via direct inputs of CO2 and degradation of organic matter. Thus, from this viewpoint reducing wastewater discharge or lowering CO2 levels in discharged wastewater may be important paths to enhancing the CO2 uptake by coastal oceans in the future.

Ganglioside-Functionalized Nanoparticles for Chimeric Antigen Receptor T-Cell Activation at the Immunological Synapse.

Chimeric Antigen Receptor (CAR) T cell therapy has proven to be an effective strategy against hematological malignancies but persistence and activity against solid tumors must be further improved. One emerging strategy for enhancing efficacy is based on directing CAR T cells to antigen presenting cells (APCs). Activation of CAR T cells at the immunological synapse (IS) formed between APC and T cell is thought to promote strong, persistent antigen-specific T cell-mediated immune responses but requires integration of CAR ligands into the APC/T-cell interface. Here, we demonstrate that CAR ligand functionalized, lipid-coated, biodegradable polymer nanoparticles (NPs) that contain the ganglioside GM3 (GM3-NPs) bind to CD169 (Siglec-1)-expressing APCs and localize to the cell contact site between APCs and CAR T cells upon initiation of cell conjugates. The CD169+ APC/CAR T-cell interface is characterized by a strong optical colocalization of GM3-NPs and CARs, enrichment of F-actin, and recruitment of ZAP-70, indicative of integration of GM3-NPs into a functional IS. Ligands associated with GM3-NPs localized to the APC/T-cell contact site remain accessible to CARs and result in robust T-cell activation. Overall, this work identifies GM3-NPs as a potential antigen delivery platform for active targeting of CD169 expressing APCs and enhancement of CAR T-cell activation at the NP-containing IS.

Non-invasive real-time monitoring of cell concentration and viability using Doppler ultrasound.

Bioprocess optimization towards higher productivity and better quality control relies on real-time process monitoring tools to measure process and culture parameters. Cell concentration and viability are among the most important parameters to be monitored during bioreactor operations that are typically determined using optical methods on an extracted sample. In this paper, we have developed an online non-invasive sensor to measure cell concentration and viability based on Doppler ultrasound. An ultrasound transducer is mounted outside the bioreactor vessel and emits a high frequency tone burst (15 MHz) through the vessel wall. Acoustic backscatter from cells in the bioreactor depends on cell concentration and viability. The backscattered signal is collected through the same transducer and analyzed using multivariate data analysis (MVDA) to characterize and predict the cell culture properties. We have developed accurate MVDA models to predict the Chinese hamster ovary (CHO) cell concentration in a broad range from 0.1 × 106 cells/mL to 100 × 106 cells/mL, and cell viability from 3% to 99%. The non-invasive monitoring is ideal for single use bioreactor and the in-situ measurements removes the burden for offline sampling and dilution steps. This method can be similarly applied to other suspension cell culture modalities.

Characterizing Lipid-Coated Mesoporous Silica Nanoparticles as CD169-Binding Delivery System for Rilpivirine and Cabotegravir.

Herein, lipid-coated mesoporous silica nanoparticles (LMSN) are investigated as biomimetic delivery vehicle for two antiretroviral compounds (ARVs), rilpivirine (RPV) and cabotegravir (CAB). Monosialodihexosylganglioside (GM3) is incorporated into the membrane to facilitate LMSN binding to CD169 (Siglec-1)-expressing myeloid cells, that are predominantly expressed in secondary lymphoid tissues in vivo. It is demonstrated that in addition to providing CD169-binding functionalities, the lipid membrane around the silica core provides stealth properties that dampen the inflammatory cytokine response to ARVs-loaded LMSN in human monocyte-derived macrophages. Quantification of RPV and CAB releases from nanoparticles, and assessment of antiviral potency to human immunodeficiency virus (HIV-1) infection in vitro reveals that RPV and CAB co-formulated into LMSN retain optimal antiviral potency for 90 days, even upon storage at room temperature, making LMSN an attractive nanoplatform, immune to cold chain requirements. These findings suggest that GM3-LMSN equip the mesoporous silica nanoparticle (MSN) core with lipid-derived properties for surface passivation and lipid-mediated binding that are of high interest for achieving an effective delivery of ARVs to tissue reservoirs of HIV-1 replication.

Variations in dissolved inorganic carbon species in effluents from large-scale municipal wastewater treatment plants (Qingdao, China) and their potential impacts on coastal acidification.

With rapid development of global wastewater treatment plants (WWTPs), acidification and enhanced CO2 release in receiving waters caused by high-CO2 treated wastewater input have raised concerns. Insights into the variations in dissolved inorganic carbon (DIC) species in treated wastewater contribute to understanding the mechanisms of the acidification process. Here, we investigated three large-scale municipal WWTPs that discharged into the coast of Qingdao, China, for variations in effluent DIC species and their control mechanisms. The results showed that the effluent DIC concentrations, with a range of 2554-5718 µmol/L, significantly exceeded the concentration in seawater and mainly increased from winter to spring and decreased from summer to autumn. The effluent DIC and its δ13CDIC showed a good negative correlation. The ratios of effluent DIC to total alkalinity (DIC/TAlk) ranged from 1.00 to 1.24, and the proportions of CO2 in DIC ranged from 0.9 to 19.7%; both sets of values significantly exceeded those in seawater. The proportions of CO32- in DIC were only ~ 0.4%. These features determined that the CO2 concentrations in effluents fluctuated from 3 to 80 times the concentration in seawater, whereas the CO32- concentrations were less than 1/15 of those in seawater. Organic matter degradation and nitrogen removal processes made important contributions to the high effluent CO2 concentrations. The increase in solubility induced by decreased temperature may be the main cause for the higher effluent CO2 concentrations during winter as well as spring months with low effluent temperatures. Correspondingly, the effluent pH values were significantly lower than the seawater pH values and showed a good negative logarithmic correlation with the DIC/TAlk values, reflecting the control of DIC species on the pH values in treated wastewater. Variations in DIC species in treated wastewater can cause changes in the affected region and the degree of the induced acidification in receiving waters.