Microbial Diversity and Community Structure of Chinese Fresh Beef during Cold Storage and Their Correlations with Off-Flavors.

To investigate the diversity and dynamics of microorganisms in Chinese fresh beef (CFB) without acid discharge treatment during cold storage, high-throughput sequencing was employed to analyze the CFB refrigerated for 0, 3, 7, and 10 days. The results showed that the community richness of the fungi and bacteria decreased significantly. However, the diversity decreased in the early stage and increased in the later stage. At the phylum level, Ascomycota (74.1-94.1%) and Firmicutes (77.3-96.8%) were the absolutely dominant fungal and bacterial phyla. The relative abundance of both fungal and bacterial phyla displayed a trend of increasing and then decreasing. At the genus level, Candida (29.3-52.5%) and Lactococcus (19.8-59.3%) were, respectively, the dominant fungal and bacterial genera. The relative abundance of Candida showed a trend of increasing and then decreasing, while Lactococcus possessed the opposite trend. KEGG metabolic pathways analysis suggested that carbohydrate metabolism, membrane transport, and amino acid metabolism were the major metabolic pathways of bacteria. Bugbase prediction indicated the major microbial phenotype of bacteria in CFB during cold storage was Gram-positive (17.2-31.6%). Correlation analysis suggested that Lactococcus, Citrobacter, Proteus, and Rhodotorula might be the main microorganisms promoting the production of off-flavor substances in CFB. This study provides a theoretical basis for the preservation of Chinese fresh beef.

Identification of FTY720 and COH29 as novel topoisomerase I catalytic inhibitors by experimental and computational studies.

The development of novel topoisomerase I (TOP1) inhibitors is crucial for overcoming the drawbacks and limitations of current TOP1 poisons. Here, we identified two potential TOP1 inhibitors, namely, FTY720 (a sphingosine 1-phosphate antagonist) and COH29 (a ribonucleotide reductase inhibitor), through experimental screening of known active compounds. Biological experiments verified that FTY720 and COH29 were nonintercalative TOP1 catalytic inhibitors that did not induce the formation of DNA-TOP1 covalent complexes. Molecular docking revealed that FTY720 and COH29 interacted favorably with TOP1. Molecular dynamics simulations revealed that FTY720 and COH29 could affect the catalytic domain of TOP1, thus resulting in altered DNA-binding cavity size. The alanine scanning and interaction entropy identified Arg536 as a hotspot residue. In addition, the bioinformatics analysis predicted that FTY720 and COH29 could be effective in treating malignant breast tumors. Biological experiments verified their antitumor activities using MCF-7 breast cancer cells. Their combinatory effects with TOP1 poisons were also investigated. Further, FTY720 and COH29 were found to cause less DNA damage compared with TOP1 poisons. The findings provide reliable lead compounds for the development of novel TOP1 catalytic inhibitors and offer new insights into the potential clinical applications of FTY720 and COH29 in targeting TOP1.

Zirconium-porphyrin-MOF-based oxidase-like nanozyme with oxygen vacancy for aflatoxin B1 colorimetric sensing.

In this study, a porous coordination network zirconium-porphyrin-based nanoparticle with oxygen vacancies (OVs) was prepared using acetic acid and benzoic acid as modulators via a simple hydrothermal method. The presence of OVs was confirmed by various characterization methods and was found to enhance oxygen uptake and activation. This resulted in the generation of more reactive peroxyl radicals (•O2 -) and led to an improved oxidase (OXD) mimetic activity. Additionally, it promoted 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) oxidation, with a low Km value of 0.07 mM and a high Vmax of 1.47 × 10-7 M·s-1. As aflatoxin B1 (AFB1) inhibits the Pt@PCN-222-ABTS nanozyme system, a colorimetric probe for AFB1 detection was constructed. The limit of detection (LOD) was 0.074 µg·L-1. This research presents a novel approach for designing a nanozymatic-based colorimetric method to analyze trace AFB1 residues in food.

Characterization of three-dimensional surface-breaking slots based on regression analysis of ultrasonic Rayleigh wave simulations.

Rayleigh waves travel along the surface of a solid structure, with most of their energy focusing within a depth of one wavelength. Thus, the reflection coefficient from a surface-breaking crack is highly sensitive to the ratio between the crack depth and the wavelength. It is possible to characterize the depth of surface-breaking cracks by measuring the features in the reflected waves. However, a feature value can correspond to multiple depth-wavelength ratios, i.e., the mapping is non-univalent, which brings difficulties for crack sizing using the feature. In this work, we use finite element method (FEM) software to perform 3-D numerical analysis on the interaction between Rayleigh waves and surface-breaking slots with various 3-D geometries. Multiple features are selected based on the nearest neighbour regression analysis on a numerical dataset, ensuring that a univalent mapping relationship from the selected features to the slot depth can be established. This relationship is then experimentally used to predict the depth of real slots with different geometries, showing reasonable accuracy.

In-situ sparse-array imaging for through-thickness cracks in plates with A0 Lamb waves and an efficient waveform inversion algorithm.

Structural health monitoring (SHM) requires efficient online crack detection and characterization to prevent structural failures, which mainly arise from fatigue cracks. Existing solutions for crack characterization involve analyzing sensed wave signals directly, but these approaches usually require onerous steps or many sensors to obtain sufficient and clear wave packets. An alternative strategy is a model-based inversion, which takes the full waveform into consideration and does not require analysis on a single wave packet. This approach can achieve accurate characterization with fewer sensors and simpler implementation. We propose an efficient model based on the Huygens' principle and the no-mode-conversion property of the A0 mode Lamb waves to meet the requirements of online monitoring. We then verify the proposed model-based crack imaging method through simulation and experiments on smooth and rough cracks. The proposed method is easy, cheap, and efficient, making it a desirable option for SHM tasks.

Magnetoactive Millirobots with Ternary Phase Transition.

Magnetoactive soft millirobots have made significant advances in programmable deformation, multimodal locomotion, and untethered manipulation in unreachable regions. However, the inherent limitations are manifested in the solid-phase millirobot as limited deformability and in the liquid-phase millirobot as low stiffness. Herein, we propose a ternary-state magnetoactive millirobot based on a phase transitional polymer embedded with magnetic nanoparticles. The millirobot can reversibly transit among the liquid, solid, and viscous-fluid phases through heating and cooling. The liquid-phase millirobot has elastic deformation and mobility for unimpeded navigation in a constrained space. The viscous-fluid phase millirobot shows irreversible deformation and large ductility. The solid-phase millirobot shows good shape stability and controllable locomotion. Moreover, the ternary-state magnetoactive millirobot can achieve prominent capabilities including stiffness change and shape reconfiguration through phase transition. The millirobot can perform potential functions of navigation in complex terrain, three-dimensional circuit connection, and simulated treatment in a stomach model. This magnetoactive millirobot may find new applications in flexible electronics and biomedicine.

Ultrasound and defect engineering-enhanced nanozyme with high laccase-like activity for oxidation and detection of phenolic compounds and adrenaline.

Perusing metal-based redox nanozyme offers new opportunity for pollutant removal and biosensor, but ultrasound (US)-driven laccase-like nanozyme remains a significant challenge, especially in combination with defect engineering strategy. Herein, the Cu2Ov@Ce-TCPP was synthesized by doping Ce3+ on the surface of Cu2O nanocube and then coating with the porphyrin sonosensitizer. The Ce-doped porphyrin metal-structure in nanozyme was demonstrated to generate oxygen vacancy defects, which could obviously promote the laccase-like activity of Cu2Ov@Ce-TCPP nanozyme under US. XPS characterization and density functional theory (DFT) theoretical calculation revealed that the ultrasonic stimulation is beneficial to accelerate the electron transfer rate and O2 adsorption to improve catalytic activity, and Cu2Ov@Ce-TCPP nanozyme exhibits low adsorption energy and activation energy due to the presence of oxygen defect site, resulting in high laccase-like activity. The interaction between Ce atom and porphyrin structure also improved the sonocatalytic ability of the nanozyme. Meanwhile, Cu2Ov@Ce-TCPP nanozyme has been used for detecting and degrading a series of phenolic compounds. The detection adrenaline method has a linear range of 3.3-1000 µM and a detection limit as low as 0.96 µM with good reproducibility. The developed US-enhancing and recyclable laccase-like nanozyme system provides a promising strategy for the oxidation and detection of phenolic compounds.

Simplified wetting boundary scheme in phase-field lattice Boltzmann model for wetting phenomena on curved boundaries.

In this work, a simplified wetting boundary scheme in the phase-field lattice Boltzmann model is developed for wetting phenomena on curved boundaries. The proposed scheme combines the advantages of the fluid-solid interaction scheme and geometric scheme-easy to implement (no need to interpolate the values of parameters exactly on solid boundaries and find proper characteristic vectors), the value of contact angle can be directly prescribed, and no unphysical spurious mass layer-and avoids mass leakage. Different from previous works, the values of the order parameter gradient on fluid boundary nodes are directly determined according to the geometric formulation rather than indirectly regulated through the order parameters on ghost solid nodes (i.e., ghost contact-line region). For this purpose, two numerical approaches to evaluate the order parameter gradient on fluid boundary nodes are utilized, one with the prevalent isotropic central scheme and the other with a local gradient scheme that utilizes the distribution functions. The simplified wetting boundary schemes with both numerical approaches are validated and compared through several numerical simulations. The results demonstrate that the proposed model has good ability and satisfactory accuracy to simulate wetting phenomena on curved boundaries under large density ratios.

Assembling High-Quality Lymph Node Clinical Target Volumes for Cervical Cancer Radiotherapy Using a Deep Learning-Based Approach.

AIM: The study aimed to explore an approach for accurately assembling high-quality lymph node clinical target volumes (CTV) on CT images in cervical cancer radiotherapy with the encoder-decoder 3D network. METHODS: 216 cases of CT images treated at our center between 2017 and 2020 were included as a sample, which were divided into two cohorts, including 152 cases and 64 controls, respectively. Para-aortic lymph node, common iliac, external iliac, internal iliac, obturator, presacral, and groin nodal regions were delineated as sub-CTV manually in the cohort including 152 cases. Then, the 152 cases were randomly divided into training (96 cases), validation (36 cases), and test (20 cases) groups for the training process. Each structure was individually trained and optimized through a deep learning model. An additional 64 cases with 6 different clinical conditions were taken as examples to verify the feasibility of CTV generation based on our model. Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics were both used for quantitative evaluation. RESULTS: Comparing auto-segmentation results to ground truth, the mean DSC value/HD was 0.838/7.7mm, 0.853/4.7mm, 0.855/4.7mm, 0.844/4.7mm, 0.784/5.2mm, 0.826/4.8mm and 0.874/4.8mm for CTV_PAN, CTV_common iliac, CTV_internal iliac, CTV_external iliac, CTV_obturator, CTV_presacral, and CTV_groin, respectively. The similarity comparison results of six different clinical situations were 0.877/4.4mm, 0.879/4.6mm, 0.881/4.2mm, 0.882/4.3mm, 0.872/6.0mm, and 0.875/4.9mm for DSC value/HD, respectively. CONCLUSION: We have developed a deep learning-based approach to segmenting lymph node sub-regions automatically and assembling high-quality CTVs according to clinical needs in cervical cancer radiotherapy. This work can increase the efficiency of the process of cervical cancer detection and treatment.

SARS-CoV-2 viral dynamic modeling to inform model selection and timing and efficacy of antiviral therapy.

Mathematical models of viral dynamics have been reported to describe adequately the dynamic changes of severe acute respiratory syndrome-coronavirus 2 viral load within an individual host. In this study, eight published viral dynamic models were assessed, and model selection was performed. Viral load data were collected from a community surveillance study, including 2155 measurements from 162 patients (124 household and 38 non-household contacts). An extended version of the target-cell limited model that includes an eclipse phase and an immune response component that enhances viral clearance described best the data. In general, the parameter estimates showed good precision (relative standard error <10), apart from the death rate of infected cells. The parameter estimates were used to simulate the outcomes of a clinical trial of the antiviral tixagevimab-cilgavimab, a monoclonal antibody combination which blocks infection of the target cells by neutralizing the virus. The simulated outcome of the effectiveness of the antiviral therapy in controlling viral replication was in a good agreement with the clinical trial data. Early treatment with high antiviral efficacy is important for desired therapeutic outcome.

Identification of N-(3-(methyl(3-(orotic amido)propyl)amino)propyl) oleanolamide as a novel topoisomerase I catalytic inhibitor by rational design, molecular dynamics simulation, and biological evaluation.

DNA topoisomerase I (TOP1) catalytic inhibitors are a promising class of antitumor agents. Oleanolic acid derivatives are potential TOP1 catalytic inhibitors. However, their inhibitory activity still needs to be enhanced, and the stability and hotspot residue sites of their interaction with TOP1 remain to be elucidated. Herein, a novel oleanolic acid derivative, OA4 (N-(3-(methyl(3-(orotic amido)propyl)amino)propyl)oleanolamide), was identified by rational design. Subsequently, molecular dynamics simulations were performed to explore the stability and conformational dynamics of the TOP1-OA4 complex. The molecular mechanics/generalized Born surface area method calculated the binding free energy and predicted Arg488, Ile535, and His632 to be hotspot residues. Biological experiments verified that OA4 is a nonintercalative TOP1 catalytic inhibitor. OA4 exhibits better proliferation inhibitory activity against tumor cells than normal cells. Furthermore, OA4 can induce apoptosis and effectively suppress the proliferation and migration of cancer cells. This work provides new insights for the development of novel TOP1 catalytic inhibitors.

Oxidative aromatization mechanism of ligustilide.

The aromatization mechanisms of ligustilide (1), a versatile monomeric phthalide, were investigated. DFT calculations combined with control experiments prove that the aromatization could result from direct oxidation by triplet oxygen in mild conditions with no catalyst, which is generally thought to be difficult. Moreover, it is predicted that the aromatization could rapidly clear away the harmful-to-organism singlet oxygen, which may be relevant to the general antioxidation activity of phthalides, providing a new point of view to understand the bioactivity from chemical reaction.

Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.

T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

On-Chip E00-E20 Mode Converter Based on Multi-Mode Interferometer.

Mode converters is a key component in mode-division multiplexing (MDM) systems, which plays a key role in signal processing and multi-mode conversion. In this paper, we propose an MMI-based mode converter on 2%-Δ silica PLC platform. The converter transfers E00 mode to E20 mode with high fabrication tolerance and large bandwidth. The experimental results show that the conversion efficiency can exceed -1.741 dB with the wavelength range of 1500 nm to 1600 nm. The measured conversion efficiency of the mode converter can reach -0.614 dB at 1550 nm. Moreover, the degradation of conversion efficiency is less than 0.713 dB under the deviation of multimode waveguide length and phase shifter width at 1550 nm. The proposed broadband mode converter with high fabrication tolerance is promising for on-chip optical network and commercial applications.

[Study on the sensitivity of a volumetric modulated arc therapy plan verification equipment on multi-leaf collimator opening and closing errors and its gamma pass rate limit].

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.

CRISPR-Cas13d effectively targets SARS-CoV-2 variants, including Delta and Omicron, and inhibits viral infection.

The recent pandemic of variants of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for innovative anti-SARS-CoV-2 approaches in addition to vaccines and antiviral therapeutics. Here, we demonstrate that a CRISPR-Cas13-based strategy against SARS-CoV-2 can effectively degrade viral RNA. First, we conducted a cytological infection experiment, screened CRISPR-associated RNAs (crRNAs) targeting conserved regions of viruses, and used an in vitro system to validate functional crRNAs. Reprogrammed Cas13d effectors targeting NSP13, NSP14, and nucleocapsid transcripts achieved >99% silencing efficiency in human cells which are infected with coronavirus 2, including the emerging variants in the last 2 years, B.1, B.1.1.7 (Alpha), D614G B.1.351 (Beta), and B.1.617 (Delta). Furthermore, we conducted bioinformatics data analysis. We collected the sequence information of COVID-19 and its variants from China, and phylogenetic analysis revealed that these crRNA oligos could target almost 100% of the SARS-CoV family, including the emerging new variant, Omicron. The reprogrammed Cas13d exhibited high specificity, efficiency, and rapid deployment properties; therefore, it is promising for antiviral drug development. This system could possibly be used to protect against unexpected SARS-CoV-2 variants carrying multiple mutations.

Activating Blood Circulation, Anti-Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling.

Leonurus japonicus Houtt. has been traditionally used to treat many ailments. This study evaluated the activating blood circulation, anti-inflammatory, and diuretic effects of L. japonicus extract (LJ) and identified its phytochemicals. In this work, the phytochemicals in LJ were identified using liquid chromatography mass spectrometry. Rats were randomly assigned to three groups (n=8): Control group was treated with saline, while the Model group (saline) and LJ group (426 mg/kg) had induced traumatic injury. All rats were treated with once by daily oral gavage for one week. The biochemical indices and protein expression were measured. Herein, 79 constituents were identified in LJ, which were effective in elevating body weight, food consumption, water intake, and urinary excretion volume, as well as in ameliorating traumatic muscle tissues in model rats. In addition, LJ prominently decreased the contents of plasma viscosity, platelet aggregation rate, thrombin time, prothrombin time, activated partial thromboplastin time, fibrinogen, thromboxane B2 (TXB2), TXB2/6-keto-prostaglandin F1α (6-keto-PGF1α), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tissue-type PA (t-PA), and PAI-1/u-PA, while significantly increasing antithrombin III, 6-keto-PGF1α, and t-PA contents. Furthermore, LJ notably inhibited tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, angiotensin II, antidiuretic hormone, aldosterone, aquaporin 1 (AQP1), AQP2, and AQP3 levels, and markedly elevating IL-10 and natriuretic peptide levels. Finally, LJ markedly reduced the protein expression of AQP1, AQP2, and AQP3 compared to the model group. Collectively, LJ possessed prominent activating blood circulation, anti-inflammatory, and diuretic effects, thus supporting the clinical application of L. japonicus.

Revealing the Active Constituents and Mechanisms of Semiliquidambar cathayensis Chang Roots against Rheumatoid Arthritis through Network Pharmacology, Molecular Docking, and in Vivo Experiment.

Semiliquidambar cathayensis Chang roots (SC) are traditional Chinese medicine for treating rheumatoid arthritis (RA). However, the effect and potential mechanism of SC remain unclear. This study aims to reveal the anti-RA constituents and mechanisms of SC based on network pharmacology, molecular docking, and adjuvant-induced arthritis (AIA) model rat experiment. In this work, 9 potential active constituents, including kaempferol, quercetin, naringenin, paeoniflorin, catechin, fraxin, gentianin, hesperetin, and ellagic acid 3,3',4-trimethyl ether, in SC crossed 65 target genes of RA. In addition, 28 core targets were enriched in inflammation and others, among which interleukin-17 (IL-17) and tumor necrosis factor (TNF) were the major targets. The binding of bio-constituents with IL-17 and TNF were performed using molecular docking. Rat experiment demonstrated that the extract of SC restored body weight loss, reduced arthritis score and the indices of thymus and spleen, alleviated ankle joint histopathology, decreased the levels of rheumatoid factor (RF), C-reactive protein (CRP), IL-17, TNF-α, IL-1ß, IL-6, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and matrix metalloproteinase-2 (MMP-2), whereas elevated the levels of IL-4 and IL-10. Collectively, it was the first time to comprehensively reveal the anti-RA efficacy and mechanism of SC via suppressing the inflammatory pathway based on network pharmacology, molecular docking, and experimental verification, which provide chemical and pharmacological evidences for the clinical application of SC.

Metabolic modeling of single bronchoalveolar macrophages reveals regulators of hyperinflammation in COVID-19.

SARS-CoV-2 infection induces imbalanced immune response such as hyperinflammation in patients with severe COVID-19. Here, we studied the immunometabolic regulatory mechanisms for the pathogenesis of COVID-19. We depicted the metabolic landscape of immune cells, especially macrophages, from bronchoalveolar lavage fluid of patients with COVID-19 at single-cell level. We found that most metabolic processes were upregulated in macrophages from lungs of patients with mild COVID-19 compared to cells from healthy controls, whereas macrophages from severe COVID-19 showed downregulation of most of the core metabolic pathways including glutamate metabolism, fatty acid oxidation, citrate cycle, and oxidative phosphorylation, and upregulation of a few pathways such as glycolysis. Rewiring cellular metabolism by amino acid supplementation, glycolysis inhibition, or PPARγ stimulation reduces inflammation in macrophages stimulated with SARS-CoV-2. Altogether, this study demonstrates that metabolic imbalance of bronchoalveolar macrophages may contribute to hyperinflammation in patients with severe COVID-19 and provides insights into treating COVID-19 by immunometabolic modulation.

Sensitivity of Three Patient-Specific Quality Assurance Systems to MLC Aperture Errors With Volumetric Modulated Arc Therapy.

Purpose: To compare the sensitivity of ArcCHECK (AC), portal dosimetry (PD), and an in-house logfile-based system (LF) to multileaf collimators (MLC) aperture errors and the ability to identify these errors. Methods and Materials: For 12 retrospective original head and neck volumetric modulated arc therapy (VMAT) plans, MLC aperture errors of ± 0.4mm, ± 1.2mm, ± 2mm, and ± 3mm were introduced for each plan, resulting in 96 plans with errors. AC, PD, and LF were used for the gamma evaluation at 3%/3mm, 3%/2mm, and 2%/2mm criteria. Gradient analysis was used to evaluate the sensitivity to MLC aperture errors. The area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve was used to evaluate the ability to identify MLC aperture errors and dose errors, and the optimal cut-off value to identify the error was obtained. Results: The gamma pass rate (%GP) of LF had the smallest descent gradient as the MLC error increases in any case. The descent gradient of PD was larger than AC, except for the case at the 2%/2mm criteria. For the 3%/3mm criteria, the MLC aperture errors that can be perfectly identified by AC, PD, and LF were ± 3mm, ± 2mm, and ± 1.2mm, respectively, and the average percent dose error (%DEs) of dose metrics in targets that can be perfectly identified were 4% to 5%, 3% to 4%, and 2% to 3%, respectively. For the 3%/2mm criteria, the errors that AC, PD, and LF can perfectly identify were the same as the 3%/3mm criteria. For the 2%/2mm criteria, AC can perfectly identify the MLC error of ± 2mm and the %DE of 3% to 4%. PD and LF can identify the MLC error of ± 1.2mm and the %DE of 2% to 3%. Conclusion: Different patient-specific quality assurance (PSQA) systems have different sensitivity and recognition abilities to MLC aperture errors. Institutions should formulate their own customized %GP limits based on their PSQA process through ROC or other methods.