CAR-NK cells in combination therapy against cancer: A potential paradigm.

Various preclinical and a limited number of clinical studies of CAR-NK cells have shown promising results: efficient elimination of target cells without side effects similar to CAR-T therapy. However, the homing and infiltration abilities of CAR-NK cells are poor due to the inhibitory tumor microenvironment. From the perspective of clinical treatment strategies, combined with the biological and tumor microenvironment characteristics of NK cells, CAR-NK combination therapy strategies with anti-PD-1/PD-L1, radiotherapy and chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonist, oncolytic virus, photothermal therapy, can greatly promote the proliferation, migration and cytotoxicity of the NK cells. In this review, we will summarize the targets selection, structure constructions and combinational therapies of CAR-NK cells for tumors to provide feasible combination strategies for overcoming the inhibitory tumor microenvironment and improving the efficacy of CAR-NK cells.

The frequency of imaging markers adjusted for time since symptom onset in intracerebral hemorrhage: A novel predictor for hematoma expansion.

BACKGROUND: Hematoma expansion (HE) is common in patients with intracerebral hemorrhage (ICH) and associated with a worse outcome. Imaging makers and shorter time from symptom onset are both associated with HE, but prognostic scores based on these parameters individually have not been satisfactory. We hypothesized that a score including both imaging markers of expansion, and time of onset, would improve prediction. METHODS: Patients with supratentorial ICH within 6 h after onset were consecutively recruited from six centers between January 2018 and August 2022. Three markers were used: hypodensities, the blend sign, and the island sign. We first defined frequency of imaging markers (FIM) as the relationship between the number of imaging markers and onset-to-CT time (OCT). The time-adjusted FIM was defined as the ratio of the number of imaging markers to the onset-to-initial imaging time. Multivariate analysis was performed to determine the relationship between FIM and HE. Receiver operating curve analysis was used to identify potential threshold values of FIM that optimally predict HE. In addition, the sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and the area under the curve (AUC) of the optimal cut-off in predicting HE were calculated. RESULTS: In total, 1488 patients were eligible for inclusion, of whom 418 had incident HE. Multivariate analysis showed that age, male sex, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, and FIM were independent predictors of HE (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.97-0.99; OR = 1.73, 95% CI = 1.28-2.35; OR = 0.87, 95% CI = 0.83-0.92; OR = 0.42, 95% CI = 0.28-0.62; OR = 7.82, 95% CI = 5.86-10.42, respectively). The optimal cut-off point for FIM in predicting HE was 0.63, with sensitivity, specificity, PPV, NPV, and AUC values of 0.69, 0.89, 0.71, 0.88, and 0.83, respectively. CONCLUSION: The FIM adjusted for time since symptom onset is a significant predictor of HE. Its use may allow improved prediction of those patients with ICH who develop HE, and the score may be clinically applicable in the management of patients with ICH.

Rapid Detection of SARS-CoV-2 in Clinical and Environmental Samples via a Resonant Cavity SERS Platform within 20 min.

The coronavirus disease 2019 (COVID-19) epidemic has given a warning that it is important to explore the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical specimens or environmental samples for public health strategies and future variants. The surface-enhanced Raman spectroscopy (SERS) technique was demonstrated to achieve this goal. However, the consistency of signals originating from the poor compatibility of virions with SERS hotspots remains a key scientific challenge for the practical applications of SERS. Herein, we develop a SERS platform for the ultrasensitive and rapid detection of SARS-CoV-2 antigen within 20 min by the combination of a highly consistent SERS substrate and a supervised deep learning algorithm. A V-shaped resonant cavity array (VRC) substrate was fabricated to trap SARS-CoV-2 virions in the periodic V cavity array and stimulate the integral SERS signal of the virus via a resonance coupling effect. Benefiting from the unique architecture of the VRC substrate, we were able to directly detect the SARS-CoV-2 virus with high sensitivity and high consistency. These excellent performances enabled us to identify five different kinds of SARS-CoV-2 variants and detect SARS-CoV-2 from clinical and environmental samples with high accuracies.

Optimal cut-off values of haematoma volume for predicting haematoma expansion at different intracerebral haemorrhage locations.

BACKGROUND: Haematoma expansion (HE) is a frequent manifestation of acute intracerebral haemorrhage (ICH) and is associated with early disease progression and poor functional status. Approximately 30 % of patients with ICH experience substantial HE within the first few hours of onset. OBJECTIVES: This study aimed to investigate the relationship between HE and initial volume at different locations in patients with ICH. METHODS: We investigated consecutive patients with ICH admitted to the emergency room at Xiangyang No. 1 People's Hospital between January 2018 and June 2022. Haematoma volume was calculated using a three-dimensional slicer platform. Prediction models were assessed using a logistic regression model. The Youden index was used to assess the haematoma volume cut-off values for predicting HE. RESULTS: This study included 306 patients: 161 had basal ganglia ICH, 41 lobar ICH, and 104 thalamic ICH. The area under the ROC curve (AUC) for the thalamic ICH score in predicting intraventricular haemorrhage (IVH) expansion ≥ 1 mL or delayed IVH expansion was 0.786, and the best cut-off value was 7.05 mL (specificity, 85.3 %; sensitivity, 62.8 %; and accuracy, 76.0 %). The AUC for the thalamic ICH and lobar ICH scores in predicting haematoma or IVH expansion were 0.756 and 0.653, respectively; the best cut-offs were 7.05 mL for the thalamus (specificity, 84.8 %; sensitivity, 60.0 %; and accuracy, 74.0 %) and 31.89 mL in the lobar area (specificity, 81.8 %; sensitivity, 52.3 %; and accuracy, 68.3 %). CONCLUSIONS: Initial ICH volume predicted haematoma or IVH expansion at different locations. Moreover, it can assist clinicians in determining whether patients are suitable for future surgical interventions or other procedures.

Predicting model of mild and severe types of COVID-19 patients using Thymus CT radiomics model: A preliminary study.

OBJECTIVE: To predict COVID-19 severity by building a prediction model based on the clinical manifestations and radiomic features of the thymus in COVID-19 patients. METHOD: We retrospectively analyzed the clinical and radiological data from 217 confirmed cases of COVID-19 admitted to Xiangyang NO.1 People's Hospital and Jiangsu Hospital of Chinese Medicine from December 2019 to April 2022 (including 118 mild cases and 99 severe cases). The data were split into the training and test sets at a 7:3 ratio. The cases in the training set were compared in terms of clinical data and radiomic parameters of the lasso regression model. Several models for severity prediction were established based on the clinical and radiomic features of the COVID-19 patients. The DeLong test and decision curve analysis (DCA) were used to compare the performances of several models. Finally, the prediction results were verified on the test set. RESULT: For the training set, the univariate analysis showed that BMI, diarrhea, thymic steatosis, anorexia, headache, findings on the chest CT scan, platelets, LDH, AST and radiomic features of the thymus were significantly different between the two groups of patients (P < 0.05). The combination model based on the clinical and radiomic features of COVID-19 patients had the highest predictive value for COVID-19 severity [AUC: 0.967 (OR 0.0115, 95%CI: 0.925-0.989)] vs. the clinical feature-based model [AUC: 0.772 (OR 0.0387, 95%CI: 0.697-0.836), P < 0.05], laboratory-based model [AUC: 0.687 (OR 0.0423, 95%CI: 0.608-0.760), P < 0.05] and model based on CT radiomics [AUC: 0.895 (OR 0.0261, 95%CI: 0.835-0.938), P < 0.05]. DCA also confirmed the high clinical net benefits of the combination model. The nomogram drawn based on the combination model could help differentiate between the mild and severe cases of COVID-19 at an early stage. The predictions from different models were verified on the test set. CONCLUSION: Severe cases of COVID-19 had a higher level of thymic involution. The thymic differentiation in radiomic features was related to disease progression. The combination model based on the radiomic features of the thymus could better promote early clinical intervention of COVID-19 and increase the cure rate.

Ethanol Electrooxidation on an Island-Like Nanoporous Gold/Palladium Electrocatalyst in Alkaline Media: Electrocatalytic Properties and an In Situ Surface-Enhanced Raman Spectroscopy Study.

The design of electrocatalysts with high activity and the understanding of the reaction mechanism for the ethanol oxidation reaction (EOR) are pivotal for commercializing direct ethanol fuel cells (DEFCs). Herein, island-like nanoporous gold/palladium (INPG/Pd) is designed as a highly efficient EOR electrocatalyst. For a better understanding of the reaction mechanism, in situ surface-enhanced Raman spectroscopy (SERS) in conjunction with H-D isotope replacement is used to investigate the dissociation and oxidation of CH3CH2OH on the INPG/Pd electrode, with a focus on identifying significant intermediate species in the reaction process. The results show that INPG/Pd has a higher electrocatalytic performance than INPG and indium-tin oxide (ITO) glass/palladium (Pd) due to the synergistic effect of NPG and Pd. INPG/Pd-10 shows the highest specific activity, the strongest charge-transfer ability, and relatively good stability. INPG/Pd presents better SERS sensitivity than ITO glass/Pd because of the plasma enhancement effect of nanoporous Au. The in situ Raman spectral results suggest that the oxidation of ethanol proceeds via a dual-pathway (C1 and C2) reaction mechanism. Dehydrogenation of ethanol can form acetaldehyde (CH3CHO) at -0.4 V. Meanwhile, the adsorbed acetaldehyde is oxidized to acetate from approximately -0.4 V, with the potential moving positively, which is the so-called C2 pathway. Alternatively, in the C1 pathway, CH3CHO and CH3CH2OH decomposed to intermediate species (adsorbed CO) on the INPG/Pd electrode due to C-C bond breaking at potentials of approximately -0.2 V. Subsequently, the CO species is oxidized to CO2 at more positive potentials.

Clinical Data-CT Radiomics-Based Model for Predicting Prognosis of Patients with Gastrointestinal Pancreatic Neuroendocrine Neoplasms (GP-NENs).

Purpose: Based on computerized tomography (CT) radiomics and clinical data, a model was established to predict the prognosis of patients with gastrointestinal pancreatic neuroendocrine neoplasms (GP-NENs). Methods: In the data collection, the clinical imaging and survival follow-up data of 225 GP-NENs patients admitted to Xiangyang No.1 People's Hospital and Jiangsu Province Hospital of Chinese Medicine from August 2015 to February 2021 were collected. According to the follow-up results, they were divided into the nonrecurrent group (n = 108) and the recurrent group (n = 117), based on which a training set and a test set were established at a ratio of 7/3. In the training set, a variety of models were established with significant clinical and imaging data (P < 0.05) to predict the prognosis of GP-NENs patients, and then these models were verified in the test set. Results: Our newly developed combined prediction model had high predictive efficacy. Univariate analysis showed that Radscore 1/2/3, age, Ki-67 index, tumor pathological type, tumor primary site, and TNM stage were risk factors for the prognosis of GP-NENs patients (all P < 0.05). The area under the receiver operating characteristic (ROC) curves (AUC) of the combined model was significantly higher [AUC:0.824, 95% CI 0.0342 (0.751-0.883)] than that of the clinical data model [AUC:0.786, 95% CI 0.0384(0.709-0.851)] and the radiomics model [AUC:0.712, 95% CI 0.0426(0.631-0.785)]. The decision curve also confirmed that the combined model had a higher clinical net benefit. The same results were achieved in the test set. Conclusion: The prognosis of patients with GP-NENs is generally poor. The combined model based on clinical data and CT radiomics can help to early predict the prognosis of patients with GP-NENs, and then necessary interventions could be provided to improve the survival rate and quality of life of patients.

Initiator enhancement of mandrel degradation for ICF target fabrication.

Poly-α-methylstyrene (PAMS), as an ideal mandrel material used in the fabrication of inertial confinement fusion (ICF) targets, its efficient degradation is the key to the quality of targets. However, there is a great challenge to achieve enhanced degradation. Here, we proposed the strategy to optimize the degradation of PAMS microspheres using di-tert-butyl peroxide (DTBP) as a degradation initiator. Experimentally, monodisperse PAMS microspheres with DTBP were controllably prepared by a microfluidic-based microencapsulation technique. Thermogravimetric results show that DTBP largely decreases the initial degradation temperature from 550 K to 450 K, which effectively promotes the thermal degradation of PAMS microspheres. Theoretically, DTBP can reduce the activation energy of degradation. Moreover, the potential energy surfaces were used to describe the degradation process at the atomic level. Our work brings a new direction for the study of mandrel degradation in ICF targets fabrication, and also provides a valuable reference for solving the pollution of waste plastics.

First Indirect Drive Experiment Using a Six-Cylinder-Port Hohlraum.

The new hohlraum experimental platform and the quasi-3D simulation model are developed to enable the study of the indirect drive experiment using the six-cylinder-port hohlraum for the first time. It is also the first implosion experiment for the six laser-entrance-hole hohlraum to effectively use all the laser beams of the laser facility that is primarily designed for the cylindrical hohlraum. The experiments performed at the 100 kJ Laser Facility produce a peak hohlraum radiation temperature of ∼222 eV for ∼80 kJ and 2 ns square laser pulse. The inferred x-ray conversion efficiency η∼87% is similar to the cylindrical hohlraum and higher than the octahedral spherical hohlraum at the same laser facility, while the low laser backscatter is similar to the outer cone of the cylindrical hohlraum. The hohlraum radiation temperature and M-band (>1.6 keV) flux can be well reproduced by the quasi-3D simulation. The variations of the yield-over-clean and the hot spot shape can also be semiquantitatively explained by the calculated major radiation asymmetry of the quasi-3D simulation. Our work demonstrates the capability for the study of the indirect drive with the six-cylinder-port hohlraum at the cylindrically configured laser facility, which is essential for numerically assessing the laser energy required by the ignition-scale six-cylinder-port hohlraum.

Bismuth impregnated biochar for efficient uranium removal from solution: Adsorption behavior and interfacial mechanism.

In this work, Bi2O3 doped horse manure-derived biochar was obtained by carbonizing the H2O2-modified horse manure loaded with bismuth nitrate under nitrogen atmosphere at 500 °C. The results showed that there was a sharp response between the as-prepared bismuth impregnated biochar and uranium(VI) species in solution, which resulted in a short equilibrium time (<80 min), a fast adsorption rate (about 5.0 mg/(g·min)), a high removal efficiency (93.9%) and a large adsorption capacity (516.5 mg/g) (T = 298 K, pH = 4, Ci = 10 mg/L and m/V = 0.1 g/L). Besides, the removal behavior of the bismuth impregnated biochar for uranium(VI) did not depend on the interfering ions and ion strength, except Al3+, Ca2+, CO32- and PO43-. These results indicated that the modified biochar might possess the potential of remediating the actual uranium(VI)-containing wastewater. Moreover, the interaction mechanism between Bi2O3 doped biochar and uranium(VI) species was further explored. The results demonstrated that the enrichment of uranium(VI) on the surface of the as-prepared biochar was controlled by various factors, such as surface complexation, ion exchange, electrostatic attraction, precipitation and reduction, which facilitated the adsorption of uranium(VI) on the bismuth impregnated biochar.

First Inertial Confinement Fusion Implosion Experiment in Octahedral Spherical Hohlraum.

In inertial confinement approaches to fusion, the asymmetry of target implosion is a major obstacle to achieving high gain in the laboratory. A recently proposed octahedral spherical hohlraum makes it possible to naturally create spherical target irradiation without supplementary symmetry control. Before any decision is made to pursue an ignition-scale laser system based on the octahedral hohlraum, one needs to test the concept with the existing facilities. Here, we report a proof-of-concept experiment for the novel octahedral hohlraum geometry on the cylindrically configured SGIII laser facility without a symmetry control. All polar and equatorial self-emission images of the compressed target show a near round shape of convergence ratio 15 under both square and shaped laser pulses. The observed implosion performances agree well with the ideal spherical implosion simulation. It also shows limitations with using the existing facilities and adds further weight to the need to move to a spherical port geometry for future ignition laser facilities.

On-Site Detection of SARS-CoV-2 Antigen by Deep Learning-Based Surface-Enhanced Raman Spectroscopy and Its Biochemical Foundations.

A rapid, on-site, and accurate SARS-CoV-2 detection method is crucial for the prevention and control of the COVID-19 epidemic. However, such an ideal screening technology has not yet been developed for the diagnosis of SARS-CoV-2. Here, we have developed a deep learning-based surface-enhanced Raman spectroscopy technique for the sensitive, rapid, and on-site detection of the SARS-CoV-2 antigen in the throat swabs or sputum from 30 confirmed COVID-19 patients. A Raman database based on the spike protein of SARS-CoV-2 was established from experiments and theoretical calculations. The corresponding biochemical foundation for this method is also discussed. The deep learning model could predict the SARS-CoV-2 antigen with an identification accuracy of 87.7%. These results suggested that this method has great potential for the diagnosis, monitoring, and control of SARS-CoV-2 worldwide.

Prediction and follow-up of risk factors for severe SARS-CoV-2 pneumonia and application of CT visual scoring.

BACKGROUND: The SARS-CoV-2 pneumonia infection is associated with high rates of hospitalization and mortality and this has placed healthcare systems under strain. Our study provides a novel method for the progress prediction, clinical treatment and prognosis of NCP, and has important clinical value for timely treatment of severe NCP patients. OBJECTIVE: To summarize the clinical features and severe illness risk factors of the patients with novel coronavirus pneumonia (NCP), in order to provide support for the progression prediction, clinical treatment and prognosis of NCP patients. MATERIALS AND METHODS: A total of 196 NCP patients treated in our hospital from January 25, 2020 to June 21, 2020 were divided into the severe group and the mild group. The clinical features of the two groups were analyzed and compared. The risk factors were explored by using multivariate logistic regression, and the receiver operating characteristic (ROC) curve was obtained. The correlations of the risk factors with the prognosis of NCP were investigated combined with the lung function test. RESULTS: The primary clinical symptoms of 196 cases of NCP included fever in 167 cases (85.2%) and cough in 121 cases (61.73%). The chest computed tomography (CT) scans of the 178 cases (90.81%) showed a typical ground-glass opacification. In 149 cases, the lymphocyte count was decreased, while the levels of creatine kinase (CK), lactate dehydrogenase (LDH), c-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and D-dimer (D-D) increased. 44 cases (22.45%) were found to be severely ill. The multivariate logistic regression analysis demonstrated that age, underlying disease, length of hospital stay, body mass index (BMI), LDH, chest CT visual score, absolute lymphocyte count (ALC) and CRP were risk factors for severe.

The synthesis of a novel titanium oxide aerogel with highly enhanced removal of uranium and evaluation of the adsorption mechanism.

A TiO2 aerogel with a high removal percentage and adsorption capacity was manufactured via template synthesis. Subsequently, the as-prepared TiO2 aerogel was characterized by various techniques and applied as an adsorbent for the removal of U(vi). The results revealed that the U(vi) adsorption was very rapid and reached apparent equilibrium within 100 min. The maximum removal percentage was 97.1%, which was calculated using the pseudo-second-order kinetic model (T = 298 K, t = 180 min, pH = 5, m/V = 0.1 g L-1 and C0 = 10 mg g-1). The Langmuir isotherm model was used to determine the maximum adsorption capacity and it achieved 638.0 mg g-1 (T = 298 K, pH = 5 and m/V = 0.1 g L-1). In addition, the removal of U(vi) on the TiO2 aerogel was relatively good in acidic solution and the removal behavior was independent of the influence of ionic strength. The removal percentage of the as-prepared TiO2 aerogel was higher than 90% after five cycles. Due to these excellent properties such as easy recovery, fast adsorption kinetics, high adsorption capacity and high removal percentage, the TiO2 aerogel might become an extremely employable adsorbent for the extraction of U(vi) in seawater.

Toward the Limitation of Dealloying: Full Spectrum Responsive Ultralow Density Nanoporous Gold for Plasmonic Photocatalytic SERS.

Plasmon-mediated chemical reaction has a great potential to create self-cleaning surface-enhanced Raman scattering (SERS) substrates. However, few works have been reported to promote this goal. Here, we report ultralow density nanoporous gold (ULDNPG) that possesses an impressive full spectrum responsive characteristic with a reflectivity lower than 5% in the waveband of 300-900 nm. ULDNPG was fabricated by a sandwich dealloying strategy from ultradilute Au-Ag solid solutions with the Au content as low as 1-5 at.%. The prepared ULDNPG presents excellent SERS properties, including high sensitivity, high uniformity, and reproducibility. The full spectrum responsive characteristic of ULDNPG leads to an obvious plasmonic photocatalytic activity. The short lifetime of the SP-excited hot carriers causes a restricted self-cleaning SERS property and a strong photothermal effect for ULDNPG structures.

First Octahedral Spherical Hohlraum Energetics Experiment at the SGIII Laser Facility.

The first octahedral spherical hohlraum energetics experiment is accomplished at the SGIII laser facility. For the first time, the 32 laser beams are injected into the octahedral spherical hohlraum through six laser entrance holes. Two techniques are used to diagnose the radiation field of the octahedral spherical hohlraum in order to obtain comprehensive experimental data. The radiation flux streaming out of laser entrance holes is measured by six flat-response x-ray detectors (FXRDs) and four M-band x-ray detectors, which are placed at different locations of the SGIII target chamber. The radiation temperature is derived from the measured flux of FXRD by using the blackbody assumption. The peak radiation temperature inside hohlraum is determined by the shock wave technique. The experimental results show that the octahedral spherical hohlraum radiation temperature is in the range of 170-182 eV with drive laser energies of 71 kJ to 84 kJ. The radiation temperature inside the hohlraum determined by the shock wave technique is about 175 eV at 71 kJ. For the flat-top laser pulse of 3 ns, the conversion efficiency of gas-filled octahedral spherical hohlraum from laser into soft x rays is about 80% according to the two-dimensional numerical simulation.

Island-like Nanoporous Gold: Smaller Island Generates Stronger Surface-Enhanced Raman Scattering.

The surface-enhanced Raman scattering properties of nanoporous gold prepared by the dealloying technique have been investigated for many years.The relatively low enhancement factor and the poor uniformity of existing conventional or advanced nanoporous gold structures are still the main factors that limit their wide application as Raman enhancement substrates. Here, we report island-like nanoporous gold (INPG) fabricated by simply controlling the composition of the dealloying precursor.This nanostructure can generate ∼10 times higher enhancement factor (above 107) with ∼4 times lower gold consumption than conventional nanoporous gold. The dimensions of the gold islands can be controlled by the composition of the precursor. The enhancement factor can therefore be controlled by the gold island dimensions, which suggests an effective approach to fabricate better Raman enhancement substrates. Furthermore, INPG exhibits excellent Raman enhancement uniformity and reproducibility with the relative standard deviations of only 2.5% and 6.5%, which originate from the extremely homogeneous structure of INPG at both the microscale and macroscale. The excellent surface-enhanced Raman scattering properties make INPG a potential surface-enhanced Raman scattering substrate.

[Study of IR Property of Glow Discharge Polymer (GDP)].

To achieve the object of NIF ignition , it is required to prepare high density fuel targets . For DD layer, IR-layering can be used to improve its surface roughness. In this paper, glow discharge polymer (GDP) flat films and capsules were synthesized. The IR absorptive properties of GDP were thoroughly studied by using infrared spectrometer and microscopy while the extinction coefficients of GDP flat film at specific wavelengths were obtained. By comparing absorption properties of flat films and capsules, it is found that thermal treatments can lower the OH content of GDP and thus improve IR layering of DD ice. Finally, the needed IR power of integration sphere were estimated by using data obtained for future DD layering experiments in this paper. The results have laid a solid foundation for the implementation of DD IR layering.