Multiple early factors anticipate post-acute COVID-19 sequelae.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

Comparative Analysis of Volatile Compounds in the Flower Buds of Three Panax Species Using Fast Gas Chromatography Electronic Nose, Headspace-Gas Chromatography-Ion Mobility Spectrometry, and Headspace Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry Coupled with Multivariate Statistical Analysis.

The flower buds of three Panax species (PGF: P. ginseng; PQF: P. quinquefolius; PNF: P. notoginseng) widely consumed as health tea are easily confused in market circulation. We aimed to develop a green, fast, and easy analysis strategy to distinguish PGF, PQF, and PNF. In this work, fast gas chromatography electronic nose (fast GC e-nose), headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), and headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) were utilized to comprehensively analyze the volatile organic components (VOCs) of three flowers. Meanwhile, a principal component analysis (PCA) and heatmap were applied to distinguish the VOCs identified in PGF, PQF, and PNF. A random forest (RF) analysis was used to screen key factors affecting the discrimination. As a result, 39, 68, and 78 VOCs were identified in three flowers using fast GC e-nose, HS-GC-IMS, and HS-SPME-GC-MS. Nine VOCs were selected as potential chemical markers based on a model of RF for distinguishing these three species. Conclusively, a complete VOC analysis strategy was created to provide a methodological reference for the rapid, simple, and environmentally friendly detection and identification of food products (tea, oil, honey, etc.) and herbs with flavor characteristics and to provide a basis for further specification of their quality and base sources.

Disulfiram/Cu Kills and Sensitizes BRAF-Mutant Thyroid Cancer Cells to BRAF Kinase Inhibitor by ROS-Dependently Relieving Feedback Activation of MAPK/ERK and PI3K/AKT Pathways.

BRAFV600E, the most common genetic alteration, has become a major therapeutic target in thyroid cancer. Vemurafenib (PLX4032), a specific inhibitor of BRAFV600E kinase, exhibits antitumor activity in patients with BRAFV600E-mutated thyroid cancer. However, the clinical benefit of PLX4032 is often limited by short-term response and acquired resistance via heterogeneous feedback mechanisms. Disulfiram (DSF), an alcohol-aversion drug, shows potent antitumor efficacy in a copper (Cu)-dependent way. However, its antitumor activity in thyroid cancer and its effect on cellular response to BRAF kinase inhibitors remain unclear. Antitumor effects of DSF/Cu on BRAFV600E-mutated thyroid cancer cells and its effect on the response of these cells to BRAF kinase inhibitor PLX4032 were systematically assessed by a series of in vitro and in vivo functional experiments. The molecular mechanism underlying the sensitizing effect of DSF/Cu on PLX4032 was explored by Western blot and flow cytometry assays. DSF/Cu exhibited stronger inhibitory effects on the proliferation and colony formation of BRAFV600E-mutated thyroid cancer cells than DSF treatment alone. Further studies revealed that DSF/Cu killed thyroid cancer cells by ROS-dependent suppression of MAPK/ERK and PI3K/AKT signaling pathways. Our data also showed that DSF/Cu strikingly increased the response of BRAFV600E-mutated thyroid cancer cells to PLX4032. Mechanistically, DSF/Cu sensitizes BRAF-mutant thyroid cancer cells to PLX4032 by inhibiting HER3 and AKT in an ROS-dependent way and subsequently relieving feedback activation of MAPK/ERK and PI3K/AKT pathways. This study not only implies potential clinical use of DSF/Cu in cancer therapy but also provides a new therapeutic strategy for BRAFV600E-mutated thyroid cancers.

Highly Soluble and Stable, High Release Rate Nanocellulose Codrug Delivery System of Curcumin and AuNPs for Dual Chemo-Photothermal Therapy.

As a natural antitumor drug, curcumin (CUR) has received increasing attention from researchers and patients due to its various medicinal properties. However, currently CUR is still restricted due to its low and stand-alone therapeutic effects that seriously limit its clinical application. Here, by using cellulose nanocrystals (CNCs) as a nanocarrier to load CUR and AuNPs simultaneously, we developed a hybrid nanoparticle as a codrug delivery system to enhance the low and stand-alone therapeutic effects of CUR. Aided with the encapsulation of ß-cyclodextrin (ßCD), both the solubility and the stability of CUR are greatly enhanced (solubility increased from 0.89 to 131.7 µg/mL). Owing to the unique rod-like morphology of CNCs, the system exhibits an outstanding loading capacity of 31.4 µg/mg. Under the heat effects of coloaded AuNPs, the system demonstrates a high release rate of 77.63%. Finally, with CNC as a bridge nanocarrier, all aforementioned functions were integrated into one hybrid nanoparticle. The all-in-one integration ensures CUR to have enhanced therapeutic effects and enables the delivery system to exhibit combined chemo-photothermal therapy outcomes. This work presents a significant step toward CUR's clinical application and provides a new strategy for effective and integrative treatment of tumor disease.

RNA-Seq Transcriptomic Analysis of Green Tea Polyphenols Modulation of Differently Expressed Genes in Enterococcus faecalis Under Bile Salt Stress.

Enterococcus faecalis (E. faecalis) belongs to lactic acid bacteria which can be used as a probiotic additive and feed, bringing practical value to the health of humans and animals. The prebiotic function of tea polyphenols lays a foundation for green tea polyphenols (GTP) to repair the adverse changes of E. faecalis under stress conditions. In this study, RNA-sequence analysis was used to explore the protective effect of GTP on E. faecalis under bile salt stress. A total of 50 genes were found to respond to GTP under bile salts stress, containing 18 up-regulated and 32 down-regulated genes. The results showed that multiple genes associated with cell wall and membrane, transmembrane transport, nucleotide transport and metabolism were significantly differentially expressed (P < 0.05), while GTP intervention can partly alleviate the detrimental effects of bile salt on amino acid metabolism and transport. The present study provides the whole genome transcriptomics of E. faecalis under bile salt stress and GTP intervention which help us understand the growth and mechanism of continuous adaptation of E. faecalis under stress conditions.

Environmental impact of express food delivery in China: the role of personal consumption choice.

The online food ordering business in China is developing rapidly in recent years with considerable environmental impacts. However, the impacts caused by the express food delivery and the differences between the regions with different economic levels have seldom been quantified. Changing personal consumption behavior might help to reduce such impacts. But to what extent personal consumption changing could alter the environmental impacts caused by express food delivery remained uncertain. Thus, we have conducted a quantitative study based on the data collected from a 45-persons survey to determine the environmental impacts caused by the express food delivery in the different regions of China. Additionally, the reducible environmental impacts were estimated by establishing a scenario of personal consumption behavior changing. The results showed that each express food delivery order would generate 111.80 g CO2 emission equivalent on average. Most (86%) of the CO2 equivalent of the express food delivery came from the food packages. Compared to the orders in the second-class and third-class cities, the orders in the first-class cities had a significantly higher CO2 equivalent due to the greater use of food packages. The results also demonstrated that by walking to take the food in the restaurants nearby (< 1 km), 68% of the CO2 equivalent derived from the express food delivery could be reduced. People's willingness to change consumption behavior plays an important role to achieve the environmental impact reduction.

Highly Thermally Stable, Green Solvent Disintegrable, and Recyclable Polymer Substrates for Flexible Electronics.

Flexible electronics require its substrate to have adequate thermal stability, but current thermally stable polymer substrates are difficult to be disintegrated and recycled; hence, generate enormous electronic solid waste. Here, a thermally stable and green solvent-disintegrable polymer substrate is developed for flexible electronics to promote their recyclability and reduce solid waste generation. Thanks to the proper design of rigid backbones and rational adjustments of polar and bulky side groups, the polymer substrate exhibits excellent thermal and mechanical properties with thermal decomposition temperature (Td,5% ) of 430 °C, upper operating temperature of over 300 °C, coefficient of thermal expansion of 48 ppm K-1 , tensile strength of 103 MPa, and elastic modulus of 2.49 GPa. Furthermore, the substrate illustrates outstanding optical and dielectric properties with high transmittance of 91% and a low dielectric constant of 2.30. Additionally, it demonstrates remarkable chemical and flame resistance. A proof-of-concept flexible printed circuit device is fabricated with this substrate, which demonstrates outstanding mechanical-electrical stability. Most importantly, the substrate can be quickly disintegrated and recycled with alcohol. With outstanding thermally stable properties, accompanied by excellent recyclability, the substrate is particularly attractive for a wide range of electronics to reduce solid waste generation, and head toward flexible and "green" electronics.

UAV Autonomous Tracking and Landing Based on Deep Reinforcement Learning Strategy.

Unmanned aerial vehicle (UAV) autonomous tracking and landing is playing an increasingly important role in military and civil applications. In particular, machine learning has been successfully introduced to robotics-related tasks. A novel UAV autonomous tracking and landing approach based on a deep reinforcement learning strategy is presented in this paper, with the aim of dealing with the UAV motion control problem in an unpredictable and harsh environment. Instead of building a prior model and inferring the landing actions based on heuristic rules, a model-free method based on a partially observable Markov decision process (POMDP) is proposed. In the POMDP model, the UAV automatically learns the landing maneuver by an end-to-end neural network, which combines the Deep Deterministic Policy Gradients (DDPG) algorithm and heuristic rules. A Modular Open Robots Simulation Engine (MORSE)-based reinforcement learning framework is designed and validated with a continuous UAV tracking and landing task on a randomly moving platform in high sensor noise and intermittent measurements. The simulation results show that when the moving platform is moving in different trajectories, the average landing success rate of the proposed algorithm is about 10% higher than that of the Proportional-Integral-Derivative (PID) method. As an indirect result, a state-of-the-art deep reinforcement learning-based UAV control method is validated, where the UAV can learn the optimal strategy of a continuously autonomous landing and perform properly in a simulation environment.

Mitigation of Inflammatory Immune Responses with Hydrophilic Nanoparticles.

While hydrophobic nanoparticles (NPs) have been long recognized to boost the immune activation, whether hydrophilic NPs modulate an immune system challenged by immune stimulators and how their hydrophilic properties may affect the immune response is still unclear. To answer this question, three polymers, poly(ethylene glycol) (PEG), poly(sulfobetaine) (PSB) and poly(carboxybetaine) (PCB), which are commonly considered hydrophilic, are studied in this work. For comparison, nanogels with uniform size and homogeneous surface functionalities were made from these polymers. Peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) and an LPS-induced lung inflammation murine model were used to investigate the influence of nanogels on the immune system. Results show that the treatment of hydrophilic nanogels attenuated the immune responses elicited by LPS both in vitro and in vivo. Moreover, we found that PCB nanogels, which have the strongest hydration and the lowest non-specific protein binding, manifested the best performance in alleviating the immune activation, followed by PSB and PEG nanogels. This reveals that the immunomodulatory effect of hydrophilic materials is closely related to their hydration characteristics and their ability to resist non-specific binding in complex media.

Revealing the Immunogenic Risk of Polymers.

Poly(ethylene glycol) (PEG) conjugation has been the gold standard to ameliorate the pharmacokinetic (PK) and immunological profiles of proteins. PEG polymer does become immunogenic once attached to proteins, evoking PEG-specific antibody (Ab) responses. The anti-PEG Abs could cause PEGylated biologic treatments to fail and even result in lethal adverse reactions. Thus the zwitterionic poly(carboxybetaine) (PCB) has been introduced as a PEG substitute for protein modification. Addressed herein is anti-polymer Ab induction by conjugating PEG and PCB polymers to a series of carrier proteins with escalating immunogenicity. Results indicate that titers of PEG-specific Abs were quantitatively correlated to the immunogenicity of carrier proteins, whereas the generation of PCB-specific Abs was minimal and insensitive to increased protein immunogenicity. This work provides insight into the immunological properties of PEG and PCB and has far-reaching implications for the development of polymer-protein conjugates.

Single-molecule studies of acidity distributions in mesoporous aluminosilicate thin films.

Solid acid catalysts are important for many petrochemical processes. The ensemble methods most often employed to characterize acid site properties in catalyst materials provide limited insights into their heterogeneity. Single-molecule (SM) fluorescence spectroscopic methods provide a valuable route to probing the properties of individual microenvironments. In this work, dual-color SM methods are adopted to study acidity distributions in mesoporous aluminosilicate (Al-Si) films prepared by the sol-gel method. The highly fluorescent pH-sensitive dye C-SNARF-1 was employed as a probe. The ratio of C-SNARF-1 emission in two bands centered at 580 and 640 nm provides an effective means to sense the pH of bulk solutions. In mesoporous thin films, SM emission data provide a measure of the effective pH of the microenvironment in which each molecule resides. SM emission data were obtained from mesoporous Al-Si films as a function of Al2O3 content for films ranging from 0% to 30% alumina. Histograms of the emission ratio reveal a broad distribution of acidity properties, with the film microenvironments becoming more acidic, on average, as the alumina content of the films increases. This work provides new insights into the distribution of Brønsted acidity in solid acids that cannot be obtained by conventional means.

Widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex.

Noninvasive neuromodulatory techniques such as transcranial direct current stimulation (tDCS) are attracting increasing interest as potential therapies for a wide range of neurological and psychiatric conditions. When targeted to the dorsolateral prefrontal cortex (DLPFC), anodal, facilitatory tDCS has been shown to improve symptoms in a range of domains including working memory, mood, and pain perception (Boggio et al., 2008a; Dockery et al., 2009; Kalu et al., 2012). However, the mechanisms underlying these promising behavioral effects are not well understood. Here, we investigated brain perfusion changes, as assessed using whole-brain arterial spin labeling (ASL), during tDCS applied to the left DLPFC in healthy humans. We demonstrated increased perfusion in regions closely anatomically connected to the DLPFC during anodal tDCS in conjunction with a decreased functional coupling between the left DLPFC and the thalami bilaterally. Despite highly similar effects on cortical excitability during and after stimulation (Nitsche and Paulus, 2000, 2001), cortical perfusion changes were markedly different during these two time periods, with widespread decreases in cortical perfusion being demonstrated after both anodal and cathodal tDCS compared to the period during stimulation. These findings may at least partially explain the different effects on behavior in these time periods described previously in the motor system (Stagg et al., 2011). In addition, the data presented here provide mechanistic explanations for the behavioral effects of anodal tDCS applied to the left DLPFC in terms of modulating functional connectivity between the DLPFC and thalami, as has been hypothesized previously (Lorenz et al., 2003).

Gallic acid promotes ferroptosis in hepatocellular carcinoma via inactivating Wnt/ß-catenin signaling pathway.

Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking ß-catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/ß-catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.

Galectin-9 as an indicator of functional limitations and radiographic joint damage in patients with rheumatoid arthritis.

Background: Previous studies have revealed that Galectin-9 (Gal-9) acts as an apoptosis modulator in autoimmunity and rheumatic inflammation. In the present study, we investigated the potential role of Gal-9 as a biomarker in patients with rheumatoid arthritis (RA), especially as an indicator of functional limitations and radiographic joint damage. Methods: A total of 146 patients with RA and 52 age- and sex-matched healthy controls were included in this study. Clinical data including disease activity, physical function, and radiographic joint damage were assessed. Functional limitation was defined as the Stanford Health Assessment Questionnaire (HAQ) disability index >1. Subjects with joint erosion >0 or joint space narrowing >0 were considered to have radiographic joint damage. Serum Gal-9 levels were detected by an enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression analysis were used to evaluate the association between Gal-9 and high disease activity and functional limitations, and a prediction model was established to construct predictive nomograms. Results: Serum levels of Gal-9 were significantly increased in patients with RA compared to those in healthy controls (median 13.1 ng/mL vs. 7.6 ng/mL). Patients with RA who were older (>65 years), had a longer disease duration (>5 years), longer morning stiffness (>60mins), elevated serum erythrocyte sedimentation rate and C-reactive protein, and difficult-to-treat RA had significantly higher Gal-9 levels than those in the corresponding control subgroups (all p <0.05). Patients with RA were divided into two subgroups according to the cut-off value of Gal-9 of 11.6 ng/mL. Patients with RA with Gal-9 >11.6 ng/mL had a significantly higher core clinical disease activity index, HAQ scores, Sharp/van der Heijde modified Sharp scores, as well as a higher percentage of advanced joint damage (all p<0.05) than patients with Gal-9 ≤11.6 ng/mL. Accordingly, patients with RA presenting either functional limitations or radiographic joint damage had significantly higher serum Gal-9 levels than those without (both p <0.05). Furthermore, multivariate logistic regression analysis showed that a serum level of Gal-9 >11.6 ng/mL was an independent risk factor for high disease activity (OR=3.138, 95% CI 1.150-8.567, p=0.026) and presence of functional limitations (OR=2.455, 95% CI 1.017-5.926, p=0.046), respectively. Conclusion: Gal-9 could be considered as a potential indicator in patients with RA, especially with respect to functional limitations and joint damage.

The mechanisms, regulations, and functions of histone lysine crotonylation.

Histone lysine crotonylation (Kcr) is a new acylation modification first discovered in 2011, which has important biological significance for gene expression, cell development, and disease treatment. In the past over ten years, numerous signs of progress have been made in the research on the biochemistry of Kcr modification, especially a series of Kcr modification-related "reader", "eraser", and "writer" enzyme systems are identified. The physiological function of crotonylation and its correlation with development, heredity, and spermatogenesis have been paid more and more attention. However, the development of disease is usually associated with abnormal Kcr modification. In this review, we summarized the identification of crotonylation modification, Kcr-related enzyme system, biological functions, and diseases caused by abnormal Kcr. This knowledge supplies a theoretical basis for further exploring the function of crotonylation in the future.

Trends in gynaecologic cancer mortality and the impact of the COVID-19 pandemic in the United States.

OBJECTIVES: Our aim was to assess the trend in gynaecologic cancer (GC) mortality in the period from 2010 to 2022 in the United States, with focus on the impact of the pandemic on increased deaths. METHODS: GC mortality data were extracted from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform. We analysed mortality trends and evaluated observed vs. predicted mortality for the period from 2020 to 2022 with joinpoint regression and prediction modelling analyses. RESULTS: A total of 334,382 deaths among adults aged 25 years and older with gynaecologic cancer were documented from 2010 to 2022. The overall age-standardised mortality rate (ASMR, per 100,000 persons) for ovarian cancer-related death decreased gradually from 7.189 in 2010 to 5.517 in 2019, yielding an APC (annual percentage change) of -2.8%. However, the decrease in ovarian cancer-related mortality slowed down by more than 4-fold during the pandemic. Cervical cancer -related mortality decreased slightly prior to the pandemic and increased during the pandemic with an APC of 0.6%, resulting in excess mortality of 4.92%, 9.73% and 2.03% in 2020, 2021 and 2022, respectively. For uterine corpus cancer, the ASMR increased from 1.905 in 2010 to 2.787 in 2019, and increased sharply to 3.079 in 2021 and 3.211 in 2022. The ASMR rose steadily between 2013 and 2022, yielding an APC of 6.9%. CONCLUSIONS: Overall, we found that GC-related mortality increased during the COVID-19 pandemic, and this increase was not specific to age, race, or ethnicity.

Multimodal PA/US imaging in Rheumatoid Arthritis: Enhanced correlation with clinical scores.

Background: Accurate assessment of Rheumatoid Arthritis (RA) activity remains a challenge. Multimodal photoacoustic/ultrasound (PA/US) joint imaging emerges as a novel imaging modality capable of depicting microvascularization and oxygenation levels in inflamed joints associated with RA. However, the scarcity of large-scale studies limits the exploration of correlating joint oxygenation status with disease activity. Objective: This study aimed to explore the correlation between multimodal PA/US imaging scores and RA disease activity, assessing its clinical applicability in managing RA. Methods: In this study, we recruited 111 patients diagnosed with RA and conducted examinations of seven small joints on their clinically dominant side using a PA/US imaging system. The PA and power Doppler ultrasound (PDUS) signals were semi-quantitatively assessed using a 0-3 grading system. The cumulative scores for PA and PDUS across these seven joints (PA-sum and PDUS-sum) were calculated. Relative oxygen saturation (So2) values of inflamed joints on the clinically dominant side were measured, and categorized into four distinct PA+So2 patterns. The correlation between PA/US imaging scores and disease activity indices was systematically evaluated. Results: Analysis of 777 small joints in 111 patients revealed that the PA-sum scores exhibited a strong positive correlation with standard clinical scores for RA, including DAS28 [ESR] (ρ = 0.682), DAS28 [CRP] (ρ = 0.683), CDAI (ρ = 0.738), and SDAI (ρ = 0.739), all with p < 0.001. These correlations were superior to those of the PDUS-sum scores (DAS28 [ESR] ρ = 0.559, DAS28 [CRP] ρ = 0.555, CDAI ρ = 0.575, SDAI ρ = 0.581, p < 0.001). Significantly, in patients with higher PA-sum scores, notable differences were observed in the erythrocyte sedimentation rate (ESR) (p < 0.01) and swollen joint count 28 (SJC28) (p < 0.01) between hypoxia and intermediate groups. Notably, RA patients in the hypoxia group exhibited higher clinical scores in certain clinical indices. Conclusion: Multi-modal PA/US imaging introduces potential advancements in RA assessment, especially regarding So2 evaluations in synovial tissues and associated PA scores. However, further studies are warranted, particularly with more substantial sample sizes and in multi-center settings. Summary: This study utilized multi-modal PA/US imaging to analyze Rheumatoid Arthritis (RA) patients' synovial tissues and affected joints. When juxtaposed with traditional PDUS imaging, the PA approach demonstrated enhanced sensitivity, especially concerning detecting small vessels in thickened synovium and inflamed tendon sheaths. Furthermore, correlations between the derived PA scores, PA+So2 patterns, and standard clinical RA scores were observed. These findings suggest that multi-modal PA/US imaging could be a valuable tool in the comprehensive assessment of RA, offering insights not only into disease activity but also into the oxygenation status of synovial tissues. However, as promising as these results are, further investigations, especially in larger and diverse patient populations, are imperative. Key points: ⸸ Multi-modal PA/US Imaging in RA: This novel technique was used to assess the So2 values in synovial tissues and determine PA scores of affected RA joints.⸸ Correlation significantly with Clinical RA Scores: Correlations significantly were noted between PA scores, PA+So2 patterns, and standard clinical RA metrics, hinting at the potential clinical applicability of the technique.

Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer.

Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation and increased humoral immunity and that they resemble TRM cells. Our results suggest NKG2A+ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.