Using single antigen specificity magnetic beads for the isolation of specific antibodies against HLA antigens.

The presence of multiple donor-specific antibodies (DSAs) targeting HLA antigens poses a challenge to transplantation. Various techniques, including the use of recombinant cell lines and crossmatch cells have been developed to isolate DSAs. To simplify the extraction of HLA-specific DSAs from complex sera, we introduced magnetic beads with single HLA specificity (MagSort). Sera were treated with MagSort, allowing HLA-specific antibodies to bind to the beads, and these specific antibodies were subsequently eluted. MagSort beads, coated with 59 different HLA variants, underwent testing through 1329 adsorption/elution processes, demonstrating their effectiveness and specificity in adsorbing and eluting HLA-specific antibodies. The MagSort method proves comparable to the cell method, showing similar isolated antibody binding patterns. The isolated antibody binding patterns from MagSort reveal both known eplets and unknown patterns, suggesting its utility for eplet discovery. Additionally, MagSort proved effective in extracting signals for flow cytometry cross-matching, offering a means to assess the binding capability of isolated antibodies against specific donor cells.

Cutaneous Hydrophilic Polymer Embolism: An Important and Overlooked Clinical Entity.

ABSTRACT: Hydrophilic polymer embolism from vascular medical devices is an underrecognized clinical entity that can cause deleterious end-organ ischemia and culminate in mortality. This is concerning as we are in the era where minimally invasive procedures are commonplace. Diagnosis is often made retrospectively after obtaining histopathological tissue samples showing endoluminal, cerebriform, amorphous, anucleate, basophilic, nonrefractile, nonpolarizable foreign body material. We detail 2 more cases of cutaneous hydrophilic polymer embolism to underscore its salient clinicopathological features and increase awareness of this important iatrogenic entity.

Iron oxide-supported gold nanoparticle electrode for simultaneous detection of arsenic and sulfide on-site.

The environmental behavior of arsenic (As) has garnered significant attention due to its hazardous nature. The fate of As often couples with sulfide, thus co-detecting arsenic and sulfide on-site is crucial for comprehending their geochemical interactions. While electrochemical methods are suitable for on-site chemical analysis, there currently exists no electrode capable of simultaneously detecting both arsenic and sulfide. To address this, we developed a dual-metal electrode consisting of iron oxide-encased carbon cloth loaded with gold nanoparticles (Au/FeOx/CC) using the electrochemical deposition method. This electrode enables square wave stripping voltammetry (SWASV) binary detection of As and sulfide. Comparison experiments reveal that the reaction sites for sulfide primarily reside on FeOx, while the interface synergy of iron oxide and gold nanoparticles enhances the response to arsenite (AsIII). Arsenate (AsV) is directly reduced to As0 on Fe0, obviating the need for an external reducing agent. The electrode achieves detection limits of 1.5 µg/L for AsV, 0.25 µg/L for AsIII, and 11.6 µg/L for sulfide at mild conditions (pH 7.8). Field validation was conducted in the Tengchong geothermal hot spring region, where the electrochemical method exhibited good correlation with the standard methods: Total As (r = 0.978 vs. ICP-MS), AsIII (r = 0.895 vs. HPLC-ICP-MS), and sulfide (r = 0.983 vs. colorimetric method). Principal component analysis and correlation analysis suggest that thioarsenic, could potentially be positive interferents for AsIII. However, this interference can be anticipated and mitigated by monitoring the abundance of sulfide. The study provides new insights and problems for the electrochemical detection of coexisted As and sulfide.

A Multienzyme Cascade Pathway Immobilized in a Hydrogen-Bonded Organic Framework for the Conversion of CO2.

The reduction of carbon dioxide to valuable chemicals through enzymatic processes is regarded as a promising approach for the reduction of carbon dioxide emissions. In this study, an in vitro multi-enzyme cascade pathway is constructed for the conversion of CO2 into dihydroxyacetone (DHA). This pathway, known as FFFP, comprises formate dehydrogenase (FDH), formaldehyde dehydrogenase (FaldDH), formolase (FLS), and phosphite dehydrogenase (PTDH), with PTDH serving as the critical catalyst for regenerating the coenzyme NADH. Subsequently, the immobilization of the FFFP pathway within the hydrogen-bonded organic framework (HOF-101) is accomplished in situ. A 1.8-fold increase in DHA yield is observed in FFFP@HOF-101 compared to the free FFFP pathway. This enhancement can be explained by the fact that within FFFP@HOF-101, enzymes are positioned sufficiently close to one another, leading to the elevation of the local concentration of intermediates and an improvement in mass transfer efficiency. Moreover, FFFP@HOF-101 displays a high degree of stability. In addition to the establishment of an effective DHA production method, innovative concepts for the tailored synthesis of fine compounds from CO2 through the utilization of various multi-enzyme cascade developments are generated by this work.

A neural signature of social support mitigates negative emotion.

Social support can mitigate the impact of distressing events. Such stress buffering elicits activity in many brain regions, but it remains unclear (1) whether this activity constitutes a stable brain signature, and (2) whether brain activity can predict buffering across people. Here, we developed a neural signature that predicted social buffering of negative emotion in response to real life stressors. During neuroimaging, participants (n = 95) responded to stressful autobiographical memories either naturally, or by imagining a conversation with a peer. Using supervised dimensionality reduction and machine learning techniques, we identified a spatio-temporal neural signature that distinguished between these two trials. Activation of this signature was associated with less negative affect across trials, and people who most activated the signature reported more supportive social connections and lower loneliness outside the lab. Together, this work provides a behaviorally relevant neurophysiological marker for social support that underlies stress buffering.

Programmable and printable formaldehyde dehydrogenase as an excellent catalyst for biodegradation of formaldehyde.

As an environmental pollutant, formaldehyde can cause serious harm to the human body. Among many degradation methods, formaldehyde dehydrogenase from Pseudomonas putida (PFDH) exhibits broad potential because of its strong catalytic specificity and high degradation efficiency. However, the real application of PFDH in industry is limited by its instability and difficulties in recycling. In this work, the suitable printing conditions for immobilizing PFDH by three-dimensional (3D) printing technology were studied: the concentration of sodium alginate (SA) was 1.635 wt%, the concentration of CaCl2 was 7.4 wt%, the crosslinking time with CaCl2 was 8 min, and the temperature of the reaction was 31.5°C. 3D-printed PFDH/calcium alginate (CA) microspheres have 210% relative enzyme activity after seven repeated uses. Dried PFDH/CA particles were characterized by scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR), EDS elemental mapping, and thermogravimetric analysis (TGA) which proved that the enzyme was immobilized by the material. In addition, the recycling ability of 3D printing to immobilize different objects was explored and different shapes were designed by computer-aided design (CAD). In conclusion, 3D printing technology was applied to immobilize PFDH in this work, which provides a new idea to biodegrade formaldehyde in a green way.

Comparative microstructural study on the teeth of Mesozoic birds and non-avian dinosaurs.

Although it is commonly considered that, in birds, there is a trend towards reduced dentition, teeth persisted in birds for 90 Ma and numerous macroscopic morphologies are observed. However, the extent to which the microstructure of bird teeth differs from other lineages is poorly understood. To explore the microstructural differences of the teeth of birds in comparison with closely related non-avialan dinosaurs, the enamel and dentine-related features were evaluated in four Mesozoic paravian species from the Yanliao and Jehol biotas. Different patterns of dentinal tubular tissues with mineralized extensions of the odontoblast processes were revealed through the examination of histological sectioning under electron microscopy. Secondary modification of the tubular structures, forming reactive sclerotic dentin of Longipteryx, and the mineralization of peritubular dentin of Sapeornis were observed in the mantle dentin region. The new observed features combined with other dentinal-associated ultrastructure suggest that the developmental mechanisms controlling dentin formation are quite plastic, permitting the evolution of unique morphologies associated with specialized feeding behaviours in the toothed birds. Proportionally greater functional stress placed on the stem bird teeth may have induced reactive dentin mineralization, which was observed more often within tubules of these taxa. This suggests modifications to the dentin to counteract potential failure.

The Fluorescence Response of Four Crystalline Starches According to Ultrasound-Assisted Starch-Salicylic Acid Inclusions.

Fluorescence has shown its superior performance in the fields of starch physicochemical properties, starch-based materials, and the interactions of starch with small molecules. However, it has not been well explored in the fluorescence characteristics of starch. Herein, the fluorescence properties of four crystalline starches (A-type tapioca starch, B-type potato starch, C-type pea starch, and V-type starch, prepared with corn starch and stearic acid) were investigated using salicylic acid (SA) as an indicator. The results of inverted fluorescence microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis indicated that SA could be included by starch. X-ray diffraction analysis further demonstrated that the inclusion of SA did not change the crystalline of the four crystal types of starches, which could provide a prerequisite for comparing the different fluorescence properties of the four crystal types of starches. Fluorescence enhancements of the four inclusions were 264.5 (B-type), 206 (C-type), 51.2 (V-type), and 28 (A-type). These results provide new insights for analyzing the fluorescence response of starch.

Enzyme-based electrochemical biosensor for antimonite detection in water.

Antimonite (SbIII) is a naturally occurring contaminant demanding on-site ultrasensitive detection. The enzyme-based electrochemical (EC) biosensors are promising, but the lack of specific SbIII oxidizing enzymes hindered the past efforts. Herein, we modulated the specificity of arsenite oxidase AioAB toward SbIII by regulating its spatial conformation from tight to loose using the metal-organic framework ZIF-8. The constructed EC biosensor, AioAB@ZIF-8, exhibited the substrate specificity toward SbIII at 12.8 s-1 µM-1, an order of magnitude higher than that of AsIII (1.1 s-1 µM-1). Relaxing AioAB structure in ZIF-8 was evidenced by the break of the S-S bond and the conversion of α helix to the random coil as suggested by Raman spectroscopy. Our AioAB@ZIF-8 EC sensor exhibited a dynamic linear range in 0.041-4.1 µM at a response time of 5 s, and the detection limit at 0.041 µM at a high sensitivity of 1894 nA µM-1. The insights into tuning the specificity of an enzyme shed new light on biosensing metal(loid)s without specific proteins.

Multicenter Validation of a Urine CXCL10 Assay for Noninvasive Monitoring of Renal Transplants.

BACKGROUND: Urine CXCL10 (C-X-C motif chemokine ligand 10, interferon gamma-induced protein 10 [IP10]) outperforms standard-of-care monitoring for detecting subclinical and early clinical T-cell-mediated rejection (TCMR) and may advance TCMR therapy development through biomarker-enriched trials. The goal was to perform an international multicenter validation of a CXCL10 bead-based immunoassay (Luminex) for transplant surveillance and compare with an electrochemiluminescence-based (Meso Scale Discovery [MSD]) assay used in transplant trials. METHODS: Four laboratories participated in the Luminex assay development and evaluation. Urine CXCL10 was measured by Luminex and MSD in 2 independent adult kidney transplant trial cohorts (Basel and TMCT04). In an independent test and validation set, a linear mixed-effects model to predict (log 10 -transformed) MSD CXCL10 from Luminex CXCL10 was developed to determine the conversion between assays. Net reclassification was determined after mathematical conversion. RESULTS: The Luminex assay was precise, with an intra- and interassay coefficient of variation 8.1% and 9.3%; showed modest agreement between 4 laboratories (R 0.96 to 0.99, P < 0.001); and correlated with known CXCL10 in a single- (n = 100 urines, R 0.94 to 0.98, P < 0.001) and multicenter cohort (n = 468 urines, R 0.92, P < 0.001) but the 2 assays were not equivalent by Passing-Bablok regression. Linear mixed-effects modeling demonstrated an intercept of -0.490 and coefficient of 1.028, showing Luminex CXCL10 are slightly higher than MSD CXCL10, but the agreement is close to 1.0. After conversion of the biopsy thresholds, the decision to biopsy would be changed for only 6% (5/85) patients showing acceptable reclassification. CONCLUSIONS: These data demonstrate this urine CXCL10 Luminex immunoassay is robust, reproducible, and accurate, indicating it can be readily translated into clinical HLA laboratories for serial posttransplant surveillance.

Neural correlates associated with conformity in adolescent and young adult men.

Social influence affects us throughout our lives, shaping our attitudes, behaviors, and preferences. Thus, the current study aimed to examine whether key age groups (adolescence versus young adulthood) were associated with differences in neural correlates associated with processing social feedback and conformity (i.e., conflict detection, positive valuation, and mentalizing) among young men. We recruited 153 participants across 5 studies, who completed a social influence task during an fMRI scan. Overall, participants were more likely to conform by changing their ratings when misaligned with others, and adolescents were more likely to conform when misaligned (compared to aligned) with others compared to young adults. Further, we found that adolescents showed increased activity in mentalizing (TPJ, dmPFC) and positive valuation regions (VS, vmPFC), compared to young adults, in response to misalignment with others. In contrast, young adults showed increased activity in conflict detection regions (AI, dACC) when exposed to feedback that they were misaligned with others and when conforming to that feedback. Overall, our results offer initial evidence that adolescent and young adult men engage different neural processes when they find out they are misaligned with others and when conforming to the recommendations of others, and this difference appears to track with brain responses in conflict detection, mentalizing and value regions. DATA STATEMENT: Raw data and analysis codes are available upon request.

One dimensional approximations of neuronal dynamics reveal computational strategy.

The relationship between neuronal activity and computations embodied by it remains an open question. We develop a novel methodology that condenses observed neuronal activity into a quantitatively accurate, simple, and interpretable model and validate it on diverse systems and scales from single neurons in C. elegans to fMRI in humans. The model treats neuronal activity as collections of interlocking 1-dimensional trajectories. Despite their simplicity, these models accurately predict future neuronal activity and future decisions made by human participants. Moreover, the structure formed by interconnected trajectories-a scaffold-is closely related to the computational strategy of the system. We use these scaffolds to compare the computational strategy of primates and artificial systems trained on the same task to identify specific conditions under which the artificial agent learns the same strategy as the primate. The computational strategy extracted using our methodology predicts specific errors on novel stimuli. These results show that our methodology is a powerful tool for studying the relationship between computation and neuronal activity across diverse systems.

Site-directed mutagenesis of HLA molecules reveals the functional epitope of a human HLA-A1/A36-specific monoclonal antibody.

Eplet 44KM is currently listed in the HLA Epitope Registry but does not adhere to the eplet definition of an amino acid configuration within a 3.5 Å radius. Eplet 44KM has been previously redefined to the antibody-verified reactivity pattern 44K/150V/158V, based on reactivity analysis of monoclonal antibody VDK1D12. Since the three residues are always simultaneously present on common HLA alleles, methods to define which residue is crucial for antibody-induction and binding are limited. In this proof-of-concept study, we performed site-directed mutagenesis to narrow down the antibody-verified reactivity pattern 44K/150V/158V to a single amino acid and defined 44K as the eplet or functional epitope of mAb VDK1D12.

Osimertinib versus platinum-pemetrexed in patients with previously treated EGFR T790M advanced non-small cell lung cancer: An updated AURA3 trial-based cost-effectiveness analysis.

Background: A recently overall survival (OS) analysis from the AURA3 trial indicated that osimertinib improves median OS versus platinum-pemetrexed for patients with previously treated epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC). Here, we assessed the cost-effectiveness of second-line osimertinib versus platinum-pemetrexed, from the perspectives of the United States payer and the Chinese health care system. Methods: A Markov model was constructed to compare the costs and health outcomes of osimertinib versus platinum-pemetrexed in second-line treatment of EGFR T790M advanced NSCLC. Life years (LYs), quality adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) were calculated. One-way and probabilistic sensitivity analyses assessed the robustness of the model. Cost-effectiveness was examined in the intention-to-treat (ITT) population and central nervous system (CNS) metastases population. Results: In the United States, compared with platinum-pemetrexed, osimertinib yielded additional effectiveness of 0.43 QALYs and -0.12 QALYs, with incremental costs of $67,588 and $16,465 in the ITT population and CNS metastases population, respectively. The ICERs of osimertinib over platinum-pemetrexed were $159,126/QALY and $-130,830/QALY, respectively. The probability of osimertinib being cost-effective was 37% and 5.76%, respectively, at the willingness-to-pay (WTP) threshold of $150,000/QALY. In China, osimertinib showed incremental effectiveness of 0.34 QALYs and -0.14 QALYs, with incremental costs of $1,663 and $-505, resulting in ICERs of $4,950/QALY and $3,754/QALY in the ITT population and CNS metastases population, respectively. At the WTP threshold of $37,489/QALY, there was a 100% and 26% likelihood that osimertinib was cost-effective in the ITT population and CNS metastases population. Conclusion: In the United States, second-line osimertinib treatment for EGFR T790M advanced NSCLC is not cost-effective compared to platinum-pemetrexed under the current WTP threshold. When the osimertinib price reduces, the economic outcome may become favorable. In China, assuming a WTP threshold of $37,489/QALY, osimertinib is the dominant treatment strategy compared with platinum-pemetrexed in the ITT population and provides cost savings for CNS metastases patients.

The interaction between autophagy and the epithelial-mesenchymal transition mediated by NICD/ULK1 is involved in the formation of diabetic cataracts.

BACKGROUND: Cataracts are the leading cause of blindness and a common ocular complication of diabetes. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) and altered autophagic activity occur during the development of diabetic cataracts. The disturbed interaction of autophagy with EMT in LECs stimulated by high glucose levels may participate in cataract formation. METHODS: A rat diabetic cataract model induced by streptozotocin (STZ) and human lens epithelial cells (HLE-B3) stimulated with a high glucose concentration were employed in the study. These models were treated with rapamycin (an inhibitor of mammalian target of rapamycin (mTOR)), and N-(N-[3,5-difluorophenacetyl]-1-alanyl)-S-phenylglycine t-butyl ester (DAPT, an inhibitor of γ-secretase) alone or in combination. Lens opacity was observed and photographed under a slit-lamp microscope. Histological changes in paraffin sections of lenses were detected under a light microscope after hematoxylin and eosin staining. Alterations of autophagosomes in LECs were counted and evaluated under a transmission electron microscope. The expression levels of proteins involved in the EMT, autophagy, and the signaling pathways in LECs were measured using Western blotting and immunofluorescence staining. Cell migration was determined by performing transwell and scratch wound assays. Coimmunoprecipitation (Co-IP) was performed to verify protein-protein interactions. Proteins were overexpressed in transfected cells to confirm their roles in the signaling pathways of interest. RESULTS: In LECs, a high glucose concentration induces the EMT by activating Jagged1/Notch1/Notch intracellular domain (NICD)/Snail signaling and inhibits autophagy through the AKT/mTOR/unc 51-like kinase 1 (ULK1) signaling pathway in vivo and in vitro, resulting in diabetic cataracts. Enhanced autophagic activity induced by rapamycin suppressed the EMT by inducing Notch1 degradation by SQSTM1/p62 and microtubule-associated protein light chain 3 (LC3) in LECs, while inhibition of the Notch signaling pathway with DAPT not only prevented the EMT but also activated autophagy by decreasing the levels of NICD, which bound to ULK1, phosphorylated it, and then inhibited the initiation of autophagy. CONCLUSIONS: We describe a new interaction of autophagy and the EMT involving NICD/ULK1 signaling, which mediates crosstalk between these two important events in the formation of diabetic cataracts. Activating autophagy and suppressing the EMT mutually promote each other, revealing a potential target and strategy for the prevention of diabetic cataracts.

High Expression of Heat Shock Protein Family D Member 1 Predicts Poor Prognosis of Esophageal Cancer.

Background: Heat shock protein family D (Hsp60) member 1 (HSPD1) has been reported as a potential survival-related biomarker in some cancers. However, the correlation between HSPD1 expression with prognosis and clinical features of esophageal cancer (EC) is poorly understood. Our research aimed to explore the clinical and prognostic significance of HSPD1 expression in EC patients. Methods: In our study, HSPD1 expression was detected by immunochemistry in 87 EC tissue specimens and 20 normal cancerous peripheral tissue specimens. Meanwhile, we also analyzed the expression of HSPD1 in EC by The Cancer Genome Atlas (TCGA) database. Then Chi-squared and Fisher's exact tests and Wilcoxon signed-rank test and logistic regression models were separately used to test the correlation between clinical characteristics and HSPD1 expression in our and TCGA cohort. Moreover, we evaluated the value of HSPD1 in prognosis by Kaplan-Meier curves and Cox analysis. Finally, gene set enrichment analysis (GSEA) was performed using the data accessed from TCGA. Results: The results showed that HSPD1 was overexpressed in EC, and the expression was related to histological type, histological grade, N classification, and clinical stage. Moreover, Kaplan-Meier curves and Cox analysis indicated that high expression of HSPD1 correlated with poor prognosis, and HSPD1 was an independent risk factor for EC. GSEA identified pathways involved in cysteine and methionine metabolism, spliceosome, selenoamino acid metabolism, mismatch repair, RNA degration, DNA replication, and cell cycle as differentially enriched in ECs with high HSPD1 expression. Conclusions: Our results suggest that HSPD1 is expressed at high levels in EC, and has potential to be used as a novel biomarker for the prognosis of patients with EC.

Tumor Cell-Specific and Lipase-Responsive Delivery of Hydrogen Sulfide for Sensitizing Chemotherapy of Pancreatic Cancer.

The inability of small molecule drugs to diffuse into tumor interstitium is responsible for the relatively low effectiveness of chemotherapy. Herein, a hydrogen sulfide (H2S) gas-involved chemosensitization strategy is proposed for pancreatic cancer treatment by developing a tumor-specific lipase-responsive nanomedicine based on aptamer-conjugated DATS/Dox co-loaded PCL-b-PEO micelle (DA/D@Ms-A). After receptor-mediated endocytosis and subsequent digestion of PCL blocks by intracellular lipase, the nanomedicine releases Dox and DATS, which then react with intracellular glutathione to produce H2S. The cytotoxicity result indicates that H2S can enhance Dox chemotherapy efficiency owing to the synergetic therapeutic effect of Dox and H2S. Moreover, the nanomedicine is featured with well tumor penetration capability benefitting from the targeting ability of aptamers and high in vivo biocompatibility due to the high density of PEO and biodegradable PCL. The nanomedicine capable of synergetic gas-chemotherapy holds great potential for pancreatic cancer treatment.

Enhancing the biocatalytic synthesis of chiral drug intermediate by rational design an aldo-keto reductase from Bacillus megaterium YC4-R4.

In recent years, with the increasing number of patients with depression, the efficient synthesis of the first-line antidepressant drug duloxetine intermediate (S-N,N-dimethyl-3-hydroxy-3-(2-thienyl)-1-propanamine, S-DHTP) has attracted great attention. The wild-type AKR3-2-9 from Bacillus megaterium YC4-R4 exhibits high application potential of catalyzing N,N-dimethyl-3-keto-3-(2-thienyl)-1-propanamine (DKTP) to prepare S-DHTP, but there is still much room for improvement. In this work, rational design was carried out to enhance the catalytic potential of AKR3-2-9. Notably, compared to the wild-type AKR3-2-9, three mutants (Ile189Val, Asn256Asp, and Ile189Val + Asn256Asp) were obtained, and their catalytic efficiencies were increased by 1.3 times, 2.3 times, and 1.31 times, respectively. Besides, the thermal stability and organic solvent resistance were improved. More importantly, when the concentration of the substrate DKTP was 0.5 g/L, the catalytic yields of Ile189Val, Asn256Asp and Ile189Val + Asn256Asp were increased by 1.45 times, 1.86 times, and 2.05 times, respectively. Besides, the corresponding optical purities of the three mutants were 92.7 %, 94.3 % and 93.8 %. The above results indicated that the rational design of the AKR of Bacillus megaterium YC4-R4 enhanced its potential for biocatalytic preparation of S-DHTP.

3D printing of recombinant Escherichia coli/Au nanocomposites as agitating paddles towards robust catalytic reduction of 4-nitrophenol.

Three-dimensional (3D) printing technology has received remarkable attention in manufacturing catalysts with tailored shapes and high precision, particularly facilitating catalyst recovery, maximizing heat/mass transfer, as well as enhancing catalytic performance. Herein, an engineered recombinant Escherichia coli strain (denoted as e-E. coli) with overexpressing metallothionein (a metal-binding protein) was explored to synthesize Au nanoparticles serving as both reducing and stabilizing agents. Then, the mixed inks containing e-E. coli/Au composite and biocompatible polymers (sodium alginate and gelatin) were extruded based on a direct ink writing method followed by chemical crosslinking to form robust 3D grids with square symmetry. To boost the mass transfer and minimize pressure drop, the monolith catalysts were assembled into agitating paddles and used for liquid-phase batch reactions (volume: 1 L). As such, the reaction solutions were mixed internally via the powered "catalytic paddles" with high mechanical strength, excellent reactivity, and easy recyclability, which could be reused at least 7 cycles without performance loss. Our work provides a novel strategy for the fabrication of supported Au catalysts, and the proof-of-concept "catalytic paddles" by 3D printing technology can be applied to other industrial solution-based reactions.

Atezolizumab compared to chemotherapy for first-line treatment in non-small cell lung cancer with high PD-L1 expression: a cost-effectiveness analysis from US and Chinese perspectives.

BACKGROUND: The IMpower110 trial revealed that atezolizumab treatment had significantly longer overall survival (OS) than chemotherapy in non-small cell lung cancer (NSCLC) patients with high-programmed death ligand 1 (PD-L1) expression. The purpose of the present study was to estimate the cost-effectiveness of atezolizumab versus platinum-based chemotherapy for first-line treatment in metastatic NSCLC with high PD-L1 expression, from the perspective of US and Chinese payers. METHODS: A partitioned survival model was constructed based on information from the IMpower110 clinical trial to estimate cost-effectiveness of atezolizumab versus chemotherapy as first-line treatment of metastatic NSCLC. Costs were estimated from US and Chinese payer perspectives. The impact of uncertainty was explored by performing one-way and probabilistic sensitivity analyses. RESULTS: In the United States, treatment with atezolizumab was estimated to increase 0.87 quality adjusted life years (QALYs) at a cost of $123,424/QALY. In China, the use of atezolizumab cost an additional $68,489 compared with chemotherapy, yielding an incremental cost-effectiveness ratio (ICER) of $78,936/QALY. Sensitivity analysis indicated that the cost of atezolizumab was the most influential factor in both countries. CONCLUSIONS: In the United States, which had a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per QALY, atezolizumab was a cost-effective strategy for first-line treatment in metastatic NSCLC patients with high PD-L1 expression when compared to chemotherapy. For China, with a WTP threshold of $33,210 per QALY, atezolizumab was not considered good-value treatment for NSCLC, and a price reduction of 52% appeared to be justified.