The Novel Fusion Protein Melittin-MIL-2 Exhibits Strong Antitumor Immune Effect in Lung Adenocarcinoma Cell A549.

In previous studies, we developed a novel fusion protein named "melittin-MIL-2" which exhibited more anti-tumor activity. However, it remains unclear whether melittin-MIL-2 possesses antitumor immune effect on lung adenocarcinoma. In this study, the immune effect and mechanism of melittin-MIL-2 inhibiting the growth and invasion of lung adenocarcinoma will be investigated, in order to provide novel perspectives for the immunotherapy of lung cancer. The results indicated that melittin-MIL-2 promoted T cell proliferation, enhanced NK cell cytotoxicity, and boosted IFN-γ secretion in PBMCs. After melittin-MIL-2 stimulation, perforin expression and LAK/NK-like killing activities of human PBMCs and NK cells were significantly enhanced. Melittin-MIL-2 is capable of hampering the development and proliferation of lung adenocarcinoma cell A549. ICAM-1 and Fas expression in A549 cells exposed to melittin-MIL-2 rose significantly. The expression levels of TLR8 and VEGF in A549 cells decreased significantly after melittin-MIL-2 stimulation. In vivo, melittin-MIL-2 substantially impeded the growth of lung adenocarcinoma and formed an immune-stimulating microenvironment locally in tumor tissues. In conclusion, the novel fusion protein melittin-MIL-2 exhibits strong anti-tumor immune effect in lung adenocarcinoma cell A549 via activating the LFA-1/ICAM-1 and Fas/FasL pathways to enhance cytolytic activity, upregulating the secretion of IFN-γ and perforin, and boosting LAK/NK-like killing activities. Immuno-effector cells and their secreted cytokines can form immune stimulation microenvironment locally in lung adenocarcinoma Lewis mice tissue.

Gender-Specific Risk Factors for Asymmetric Bone Density in Adult Degenerative Lumbar Scoliosis: A Retrospective Cohort Analysis.

BACKGROUND This study aimed to evaluate the performance of Hounsfield Unit (HU) value on the vertebral bone mineral density associated with adult degenerative lumbar scoliosis (ADLS) and to compare the HU and coronal height changes of the lumbar spine on the concave and convex sides. The secondary aim was to investigate the risk factors for increased asymmetric ratio of HU (ARH) by concave-to-convex. MATERIAL AND METHODS A total of 74 patients aged ≥50 years were retrospectively reviewed. The height and the HU values of the region of interest were measured and compared. Multiple linear regression and gender-stratified analyses were performed to explore risk factors. Restricted cubic spline (RCS) was used to visually assess the dose-effect relationship between the Cobb angle and ARH. RESULTS The heights on the concave sides were significantly lower while HU values were significantly higher than that of the convex side. Cobb angle (95% CI: 0.001 to 0.009, P=0.034) was positively correlated with the increased ARH, while apex orientation to the right (95% CI: -0.152 to -0.013, P=0.022) was negatively associated. Gender-stratified analyses showed age and apex vertebrae location are 2 additional risk factors in male patients but not in female patients. Cobb angle was identified by RCS as a risk factor both in males and females and the inflection points were 15 and 17.5, respectively. CONCLUSIONS HU values on the concave side are significantly higher than on the convex side, showing the asymmetrical bone mass distribution of ADLS patients. Several gender-related risk factors for increased ARH have been identified.

Predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion.

OBJECTIVE: The aim of this study was to investigate the predictive value of different site-specific MRI-based assessments of bone quality for cage subsidence among patients undergoing oblique lumbar interbody fusion (OLIF) with or without posterior internal fixation. METHODS: The authors retrospectively reviewed the records of patients who underwent OLIF between 2017 and 2022. Endplate bone quality (EBQ), mean vertebral bone quality (MVBQ), and vertebral bone quality (VBQ) scores were measured using preoperative non-contrast-enhanced T1-weighted MRI of the lumbar spine. Logistic regression analysis was used to identify factors associated with cage subsidence. Receiver operating characteristic curve analysis was used to evaluate the value of different site-specific MRI-based assessments of bone quality in predicting cage subsidence. RESULTS: Of the 124 patients who underwent OLIF, subsidence was found in 42 (33.9%). The VBQ, MVBQ, and EBQ scores were higher in the subsidence group than in the no-subsidence group. In the stand-alone OLIF (SA-OLIF) group, logistic regression analysis showed that the EBQ score was significantly associated with subsidence (OR 13.656, 95% CI 2.561-72.806; p = 0.002). Furthermore, the areas under the curve (AUCs) for using the VBQ, MVBQ, and EBQ scores and T-score to predict cage subsidence were 0.684, 0.683, 0.745, and 0.685, respectively. In the OLIF with posterior internal fixation (OLIF-PF) group, logistic regression analysis showed that the MVBQ score was significantly associated with subsidence (OR 8.301, 95% CI 2.064-33.385; p = 0.003). The AUCs for using the VBQ score, MVBQ score, and T-score to predict cage subsidence were 0.757, 0.774, and 0.685, respectively. CONCLUSIONS: There are significant differences in the predictive value of different site-specific bone quality assessments for cage subsidence among patients undergoing OLIF. For SA-OLIF, the EBQ score is recommended, while for OLIF-PF, the VBQ score is preferable.

The magnetic resonance imaging-based vertebral bone quality scoring system: A novel method to evaluate endplate changes in patients with primary single-level disk herniation and Modic changes.

OBJECTIVES: This study aimed to investigate differences in vertebral fat distribution and bone density between patients with and without Modic changes (MCs) using a magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) scoring system. PATIENTS AND METHODS: In this retrospective study, 189 patients (95 males, 94 females; mean age: 54±2.2 years; range, 18 to 82 years) with primary single-level disk herniation were reviewed between June 2021 and June 2022. The patients were divided into the MC group (n=99) and the non-MC (NMC) group (n=90). The subcutaneous fat tissue thickness and bone mineral density were determined. The system consisted of two scores: the VBQ score, which reflected the fatty infiltration within the vertebral body, and the endplate bone quality (EBQ) score, which reflected the signal intensity (SI) of the upper and lower endplates. The EBQ score is a novel measurement that we introduced in this study. The VBQ and EBQ were measured and scored using MRI scans. The mean SI of the upper and lower endplates (endplate SI)/the bone marrow SI (marrow SI) was measured. RESULTS: There was a considerable difference in subcutaneous fat tissue thickness between the MC and NMC groups (1.40 vs. 1.16 cm, p=0.01). The EBQ scores of the L4 and L5 vertebrae and endplate SI/marrow SI of all vertebral body levels were significantly higher in the MC group. CONCLUSION: The occurrence of MCs in the lumbar spine may be associated with abnormal fat distribution. The distribution of vertebral fat in patients with MCs is distributed earlier in the upper and lower endplates of the vertebral body, and this trend is not observed in patients without MC. The thickness of subcutaneous fat tissue is a key factor in the occurrence of MCs.

Ganoderma lucidum Polysaccharide Supplementation Significantly Activates T-Cell-Mediated Antitumor Immunity and Enhances Anti-PD-1 Immunotherapy Efficacy in Colorectal Cancer.

Ganoderma lucidum polysaccharide (GLP) is a prebiotic with immunomodulatory effects. However, the therapeutic potential of GLP in tumor immunotherapy has not been fully explored, especially in T cell-mediated antitumor immunity. In this study, we found that GLP significantly inhibited tumor growth and activated antitumor immunity in colorectal cancer (CRC). In the spleens and tumor tissues, the proportion of cytotoxic CD8+T cells and Th1 helper cells increased, while immunosuppressive Tregs decreased. Additionally, microbiota dysbiosis was alleviated by GLP, and short-chain fatty acid production was increased. Meanwhile, GLP decreased the ratio of kynurenine and tryptophan (Kyn/Trp) in the serum, which contributed to antitumor immunity of T cells. More importantly, the combination of GLP and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody further enhanced the efficacy of anti-PD-1 immunotherapy. Thus, GLP as a prebiotic has the potential to be used in tumor immunotherapy.

Iron ions-sequestrable and antioxidative carbon dot-based nano-formulation with nitric oxide release for Parkinson's disease treatment.

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp2-hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD.

Culture-free detection of ß-lactamase-Producing bacteria in urinary tract infections using a paper sensor.

Developing simple, inexpensive, fast, sensitive, and specific probes for antibiotic-resistant bacteria is crucial for the management of urinary tract infections (UTIs). We here propose a paper-based sensor for the rapid detection of ß-lactamase-producing bacteria in the urine samples of UTI patients. By conjugating a strongly electronegative group -N+(CH3)3 with the core structures of cephalosporin and carbapenem antibiotics, two visual probes were achieved to respectively target the extended-spectrum/AmpC ß-lactamases (ESBL/AmpC) and carbapenemase, the two most prevalent factors causing antibiotic resistance. By integrating these probes into a portable paper sensor, we confirmed 10 and 8 cases out of 30 clinical urine samples as ESBL/AmpC- and carbapenemase-positive, respectively, demonstrating 100% clinical sensitivity and specificity. This paper sensor can be easily conducted on-site, without resorting to bacterial culture, providing a solution to the challenge of rapid detection of ß-lactamase-producing bacteria, particularly in resource-limited settings.

Molecular characterization of Chinese patients with small bowel adenocarcinoma.

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. RESULTS AND CONCLUSIONS: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.

Characteristics of aerosol aminiums over a coastal city in North China: Insights from the divergent impacts of marine and terrestrial influences.

Aminium ions, as crucial alkaline components within fine atmospheric particles, have a notable influence on new particle formation and haze occurrence. Their concentrations within coastal atmosphere depict considerable variation due to the interplay of distinctive marine and terrestrial sources, further complicated by dynamic meteorological conditions. This study conducted a comprehensive examination of aminiums ions concentrations, with a particular focus on methylaminium (MMAH+), dimethylaminium (DMAH+), trimethylaminium (TMAH+), and triethylaminium (TEAH+) within PM2.5, over varying seasons (summer, autumn, and winter of 2019 and summer of 2021), at an urban site in the coastal megacity of Qingdao, Northern China. The investigations revealed that the total concentration of particulate aminium ions (∑Aminium) was 21.6 ± 23.6 ng/m3, exhibiting higher values in the autumn and winter compared to the two summer periods. Considering diurnal variations during autumn and winter, concentrations of particulate aminium ions (excluding TEAH+) exhibited a slight increase during the day compared to night, with a notable peak during the morning hours. However, it was not the case for TEAH+, which was argued to be readily oxidized by ambient oxidants in the afternoon. Additionally, the ∑Aminium within the summer demonstrated markedly elevated levels during the day compared to night, potentially attributed to daytime sea fog associated with sea-land breeze interactions. Positive matrix factorization results indicate terrestrial anthropogenic emissions, including vehicle emission mixed with road dust and primary pollution, as the primary sources of MMAH+ and DMAH+. Conversely, TMAH+ was predominantly emitted from agricultural and marine sources. With the dominance of sea breeze in summer, TMAH+ was identified as a primary marine emission correlated with sea salt, while MMAH+, DMAH+, and TEAH+ were postulated to undergo secondary formation. Furthermore, a notable inverse correlation was observed between TMAH+ and methanesulfonate in PM2.5, consistent with dynamic emissions of sulfur-content and nitrogen-content gases reported in the literature.

The important role of nitrate in iron and manganese dissolution and sulfate formation in fine particles at a coastal site in Northern China.

Bioavailable transition trace elements, such as soluble iron (Fes) and soluble manganese (Mns) in aerosols, play a crucial role in atmospheric sulfate formation and marine ecosystems. In this study conducted during the spring of 2017 in Qingdao, a coastal city in Northern China, we applied a combined approach of multiple linear regression (MLR) incorporating the results of positive matrix factorization (PMF) to estimate the solubility of Fe and Mn from various sources. PMF analysis showed that dust was the largest contributor to total Fe (FeT) (45.5 %), followed by non-ferrous smelting (20.3 %) and secondary formation processes (17.8 %). However, secondary formation processes (33.2 %), vehicle exhaust (19.3 %) and aqueous-phase processes (19.0 %) were found to be the primary contributors to Fes. For total Mn (MnT) and Mns, dust (21.2 % âˆ¼ 35.0 %), secondary formation processes (20.3 % âˆ¼ 25.6 %) and industry (12.6 % âˆ¼ 16.3 %) were identified as the dominant contributors. The solubilities of Fe and Mn varied significantly depending on their sources. Interestingly, nitrate played a more pronounced role than sulfate in facilitating the dissolution of Fe and Mn during the acid processing due to the high molar ratio of NO3-/2SO42- (1.72 ± 0.54) under the average RH of 56 % ± 15 %. This phenomenon suggested that the acid processing was primarily triggered by nitrate formation due to the low deliquescence relative humidity (DRH) of nitrate. Additionally, we discovered that the catalytic oxidation of SO2 in aerosol water was primarily driven by Fe rather than Mn, serving as a more significant pathway for sulfate formation within a pH range of 2.0 to 4.4. These findings provide valuable insights into the impact of acidification on the dissolution of Fe and Mn under conditions of moderate RH in the real ambient atmosphere with the increasing of NO3-/2SO42- molar ratio.

High heterogeneity and aging state of mineral particles in a slowly-moving dust plume on the southwestern coast of Japan.

Aerosol particles in two size ranges, namely 0.18-1.4 µm (fine) and larger than 1.4 µm (coarse), were collected in the pre-dust, in-dust, and post-dust air during the passage of a slowly-moving dust event at a coastal site in southwestern Japan. We identified the composition and size of individual particles using a scanning electron microscope to investigate the variations during dust passage. The particles could be classified as mineral-seasalt mixtures, non-mixture minerals, sulfur-containing minerals, and seasalt particles, and the number fractions of these type particles in the two size ranges exhibited significant variation across the three periods. In the coarse size range, mixture particles accounted for 17.6 %, 26.8 %, and 37.8 % of the particles in the pre-dust, in-dust, and post-dust air, respectively. Non-mixture particles made up 36.8 %, 29.2 %, and 24.3 % in the same respective periods. In the in-dust air, the average relative ratio of sulfur content in sulfur-containing mineral particles in the coarse range was 5.5 %, whereas in the fine range, it was 17.2 %. The aging state of sea salt components, described by the Cl loss and reflecting the changes in particles due to chemical reactions, exhibited significant differences in the two size ranges. In the fine range, the aging of >90 % particles was predominantly influenced by sulfate formation in the in-dust air. In contrast, nitrate likely played a certain role in both the pre-dust and post-dust air. In the coarse range, the aging was independent of sulfate formation. These results indicate the close dependence of the aging of dust particles on their size and the notable variations of the aged states, underscoring the essentiality to treat dust particles properly according to time and space for a better understanding on their roles in the marine atmosphere.

Rapid and visual identification of ß-lactamase subtypes for precision antibiotic therapy.

The abuse of antibiotics urgently requires rapid identification of drug-resistant bacteria at the point of care (POC). Here we report a visual paper sensor that allows rapid (0.25-3 h) discrimination of the subtypes of ß-lactamase (the major cause of bacterial resistance) for precision antibiotic therapy. The sensor exhibits high performance in identifying antibiotic-resistant bacteria with 100 real samples from patients with diverse bacterial infections, demonstrating 100% clinical sensitivity and specificity. Further, this sensor can enhance the accuracy of antibiotic use from 48% empirically to 83%, and further from 50.6% to 97.6% after eliminating fungal infection cases. Our work provides a POC testing platform for guiding effective management of bacterial infections in both hospital and community settings.

Clinical performance of AMA-M2, anti-gp210 and anti-sp100 antibody levels in primary biliary cholangitis: When detected by multiplex bead-based flow fluorescent immunoassay.

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy, characterized by the presence of some autoantibodies in the serum. This study aimed to evaluate the clinical significance of AMA-M2, anti-gp210 and anti-sp100 antibody levels detected by multiplex bead-based flow fluorescent immunoassay (MBFFI) in PBC. METHODS: This study cohort included 238 PBC patients, 81 autoimmune hepatitis (AIH) patients, 62 systemic lupus erythematosus (SLE) patients, and 118 healthy controls. Serum AMA-M2, anti-gp210 and anti-sp100 antibody were detected by MBFFI and immunoblotting assay (IBT). The relationship between three antibody levels and cirrhosis, liver function, cholestasis markers and therapeutic effect to ursodesoxycholic acid (UDCA) was evaluated in PBC. RESULTS: MBFFI were presented good coincidence rate (87.39%-95.38%) with IBT. The level of AMA-M2, anti-gp210 and anti-sp100 antibodies in PBC patients were higher than other disease group and healthy controls (p ＜ .01). When compared with the healthy controls group, the AUC of AMA-M2, anti-gp210 and anti-sp100 antibodies were 0.9245, 0.7619, and 0.6789, respectively. In addition, gp210 antibody levels have diagnostic value in patients with liver cirrhosis (AUC: 0.7567). We found that when combine detect these three antibodies, the sensitivity was higher than individually detection. High level of serum anti-gp210 antibody could be related to worse liver function and more severe cholestasis in PBC patients. Moreover, serum antibody levels may decrease or remained flat in patients who responded well to UDCA. CONCLUSION: The detection of AMA-M2, anti-gp210 and anti-sp100 antibody levels by MBFFI showed good performance in the diagnosis of PBC. Serum anti-gp210 antibody level is related to cirrhosis, poor liver function and severe cholestasis in PBC.

MRI­based vertebral bone quality score is a comprehensive index reflecting the quality of bone and paravertebral muscle.

BACKGROUND: Recently, vertebral bone quality (VBQ) score has been shown to predict bone mineral density (BMD) and spine-related postoperative complications. However, in clinical work, we found that patients with higher VBQ scores also had more severe paravertebral muscle degeneration. PURPOSE: To explore the ability of the VBQ score to evaluate BMD and paravertebral muscle quality. STUDY DESIGN/SETTING: Retrospective single-center cohort. PATIENT SAMPLE: Patients in the spinal surgery department of our hospital. OUTCOME MEASURES: Bone mineral density and T-score were measured by dual-energy X-ray absorptiometry (DXA). The Picture Archiving and Communication Systems (PACS) measured the cross-sectional area (CSA) of the paravertebral muscles. Image J software was used to measure the degree of fat infiltration (DFF) of the paraspinal muscle. METHODS: Patients who underwent lumbar MRI and DXA simultaneously within two weeks were enrolled. The VBQ score was calculated using T1-weighted lumbar MRI images. Firstly, BMD-related and muscle-related parameters of patients with different VBQ scores were compared. Then, the correlation coefficients between the VBQ score and the parameters of BMD and paravertebral muscle were calculated. Finally, multivariate linear analysis was used to compare the contribution of each variable to the VBQ score. RESULTS: A total of 101 patients were eventually included in this study for analysis. When the VBQ score was greater than 3.0, the patients were mostly female, older, less likely to smoke, and had lower BMD. Interestingly, we found that patients with VBQ scores greater than 3.0 had smaller CSA of the paravertebral muscles (ES: 17.53±3.36 vs 19.13±3.97, p=.032; total: 29.59±5.27 vs 34.12±7.02, p<.001) and higher DFF (MF: 22.47±5.93 vs 19.64±5.28, p=.015; ES: 17.71±4.67 vs 15.74±4.62, p=.038; PM: 13.70±3.32 vs 11.33±3.02, p<.001; average: 17.96±3.78 vs 15.57±3.42, p=.001). The VBQ score was negatively correlated with the CSA (MF: r=-0.316, p=.001; ES: r =-0.388, p=.001; PM: r=0.388, p=.001) and positively correlated with the DFF (MF: r=0.344, p<.001; ES: r=0.439, p<.001; PM: =0.416, p<.001). In multivariate linear analysis, BMD, total CSA, and average DFF determined the value of the VBQ score, and the contribution of paravertebral muscle was higher than that of BMD (BMD: r=-0.203, p=.024; total CSA: r=-0.294, p=.003; average DFF: r=0.261, p=.011). CONCLUSIONS: This study is the first to find a positive association between the VBQ score and paravertebral muscle degeneration, and this association may be independent of BMD. VBQ can reflect the quality of bone and paravertebral muscle, which is its special advantage in clinical application.

Sex differences in the accuracy of vertebral bone quality score assessing bone density in patients undergoing lumbar spinal fusion.

OBJECTIVE: Low bone mineral density (BMD) significantly increases the risk of complications in patients undergoing spinal fusion. Existing evidence indicates that traditional dual-energy x-ray absorptiometry (DEXA) and quantitative CT (QCT) screening are underutilized in spine surgery. The MRI-based vertebral bone quality (VBQ) score provides a tool for primary screening of bone density. The validity of this score as a predictor across sexes has not been investigated. This study aimed to explore the effect of sex on the diagnostic efficacy of the VBQ in predicting osteopenia/osteoporosis and whether a sex-specific threshold exists. METHODS: In this retrospective cohort study, patients who underwent lumbar fusion at a tertiary care center were reviewed. VBQ was obtained by noncontrast T1-weighted MRI. Patients were stratified according to sex and bone density. Data were analyzed between the groups. Pearson correlation analysis and linear regression were used to analyze the correlation between the VBQ and DEXA T values. Receiver operating characteristic (ROC) curve analysis, including area under the curve (AUC) calculation, was used to evaluate the predictive performance of VBQ for low BMD in both sexes. RESULTS: A total of 271 patients (92 male, 179 female patients) were analyzed. The correlation coefficient between VBQ and the lowest T value was -0.40 for male and -0.554 for female patients. In comparing the bone density subgroups, among male patients a significant difference in the VBQ scores was observed only between the normal and osteoporosis subgroups (p = 0.012). VBQ demonstrated statistically significant differences among female patients across all three subgroups (p < 0.001). The ROC analysis revealed that the predictive performance of VBQ in detecting low BMD was more consistent with the gold-standard DEXA results in female than in male patients (AUC 0.647 vs AUC 0.823, p = 0.02). The optimal thresholds were similar in both sexes. CONCLUSIONS: Compared with male patients, VBQ has better discrimination between female patients with low BMD and those with normal bone density. Although the correlation between VBQ and bone density is weaker in male than in female patients, the optimal thresholds are similar in both sexes.

Combinations of two imaging parameters to improve bone mineral density (BMD) assessment in patients with lumbar degenerative diseases.

PURPOSE: To explore whether combining the Hounsfield unit (HU) values and vertebral bone quality (VBQ) scores can improve the BMD assessment in patients with lumbar degenerative diseases. METHODS: The HU values were measured by CT image, and VBQ scores were calculated by lumbar MRI image. The correlations of the opportunistic imaging parameters to the lowest T-scores were analyzed. Receiver-operating characteristic curve (ROC) analysis was used to evaluate the accuracy in detecting osteoporosis. Finally, the specificity and sensitivity of different combined methods of the HU values and VBQ scores in the diagnosis of osteoporosis were compared. RESULTS: Patients with osteoporosis had the lowest HU values and the highest VBQ scores. The correlation coefficients between the VBQ scores and the T-scores were smaller than HU values (L1 HU value: 0.702; average HU value:0.700; L1 VBQ score: -0.413; VBQ score: -0.386). The areas under the curve (AUCs) of the HU values were greater than those of the VBQ scores, and the AUCs of the L1 VBQ score were similar to the VBQ score (L1 HU value: 0.850; average HU value:0.857; L1 VBQ score: 0.704; VBQ score: 0.673). When combining the two imaging parameters in series, the specificity of the detection of osteoporosis was improved (L1 HU value and L1 VBQ score: 87.3%; Average HU value and VBQ score: 85.9%). When combining the two imaging parameters in parallel, the sensitivity of the detection of osteoporosis was improved (L1 HU value or L1 VBQ score: 88.1%; Average HU value or VBQ score: 91.5%). CONCLUSIONS: Combinations of the HU values and VBQ scores could improve the diagnostic performance of osteoporosis. In addition, considering the same diagnostic performance but easier measurement, parameters at the single-segment level were recommended to assist in the diagnosis of osteoporosis.

Biomarkers and biologics related with psoriasis and psoriatic arthritis.

Over the past half century, psoriasis is considered as an immune-mediated inflammatory skin disease with the combined hallmarks of autoimmunity and autoinflammation, according to growing volumes of clinical and experimental findings. There is currently no cure for psoriasis, current treatment strategies focus on symptom control, disease minimization, and patient's quality of life enhancement. To meet these challenges, it keeps imperative to discover potential biomarkers, so that not only can they be used for the prediction and monitoring of psoriasis disease in clinic, but also can provide novel therapeutic targets or treatment strategies for psoriasis sufferers. This review systematically demonstrates the research progress of psoriasis-related biomarkers and elaborates their related mechanisms in the pathological development of psoriasis and psoriatic arthritis. In addition, we summarize the development of biologic therapies for psoriasis and psoriatic arthritis in order to drive the broader discussion of psoriasis as an autoimmune-mediated inflammatory skin disease.

Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy.

Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR)-modified T cells has revolutionized the field of immune-oncology, showing remarkable efficacy against hematological malignancies. However, its success in solid tumors is limited by factors such as easy recurrence and poor efficacy. The effector function and persistence of CAR-T cells are critical to the success of therapy and are modulated by metabolic and nutrient-sensing mechanisms. Moreover, the immunosuppressive tumor microenvironment (TME), characterized by acidity, hypoxia, nutrient depletion, and metabolite accumulation caused by the high metabolic demands of tumor cells, can lead to T cell "exhaustion" and compromise the efficacy of CAR-T cells. In this review, we outline the metabolic characteristics of T cells at different stages of differentiation and summarize how these metabolic programs may be disrupted in the TME. We also discuss potential metabolic approaches to improve the efficacy and persistence of CAR-T cells, providing a new strategy for the clinical application of CAR-T cell therapy.

Important Roles and Formation of Atmospheric Organosulfates in Marine Organic Aerosols: Influence of Phytoplankton Emissions and Anthropogenic Pollutants.

Organosulfates (OSs) could be potentially important compounds in marine organic aerosols, while their formation in marine atmospheres is far from clear due to a lack of cruise observations. In this work, shipboard atmospheric observations were conducted over the Yellow Sea and Bohai Sea to investigate the abundance and formation of biogenic isoprene/monoterpene-OSs in marine aerosols. The quantified OSs and NOSs accounted for 0.04-6.9% of marine organic aerosols and were 0.07-2.2% of the non-sea-salt (nss) sulfate in terms of sulfur content. Isoprene-related (nitrooxy-)OSs occupied 27-87% of the total quantified OSs, following the abundance order of summer > autumn > spring or winter. This order was driven by the marine phytoplankton biomass and sea surface temperature (SST), which controlled the seawater and atmospheric isoprene concentration levels. Under the severe impacts of anthropogenic pollutants from the East Asia continent in winter, monoterpene nitrooxy-OSs, generated with NOx involved in, increased to 34.4 ± 35.5 ng/m3 and contributed 68% of the quantified (nitrooxy-)OSs. Our results highlight the notable roles of biogenic OSs in marine organic aerosols over regions with high biological activity and high SST. The formation of biogenic OSs and their roles in altering marine aerosol properties calls for elaboration through cruise observations in different marine environments.

Characteristics of MRI­based vertebral bone quality scores in elderly patients with vertebral fragility fractures.

OBJECTIVE: To explore the characteristics of vertebral bone quality (VBQ) scores in patients with vertebral fragility fractures, including VBQ score and single-level VBQ score, and evaluate their effectiveness as predictors. METHODS: The VBQ scores were measured using T1-weighted MRI images. VBQ scores were compared in patients with different times of previous fragility fractures. In addition, patients with fractures were matched for age and sex with patients without fractures, and VBQ scores were compared between the two groups. Finally, the predictive efficiency of VBQ scores for vertebral fragility fractures was analyzed by the receiver-operator curve (ROC). RESULTS: The average VBQ score and single-level VBQ score in patients with fractures were 3.48 ± 0.56 and 3.60 ± 0.60 and no difference among patients with different times of previous fractures. As for the age- and sex-matched patients, fracture patients had higher VBQ scores (VBQ score: 3.48 ± 0.56 vs. 2.88 ± 0.40, p < 0.001; single-level VBQ score: 3.60 ± 0.60 vs. 2.95 ± 0.44, p < 0.001). The AUCs using the VBQ score and single-level VBQ score to predict fragility fractures were 0.815 and 0.817, respectively. The optimal thresholds of the VBQ score and single-level VBQ score for predicting fragility fractures were 3.22 and 3.16, respectively. CONCLUSION: MRI­based VBQ scores are important predictors of vertebral fragility fracture but have no predictive value for the recurrence of fractures in patients with a history of fragility fractures. The VBQ score of 3.22 and single-level VBQ score of 3.16 are optimal thresholds that can be used when using lumbar MRI scans to identify individuals at high risk for fragility fractures.