Preclinical Evaluation and a Pilot Clinical Positron Emission Tomography Imaging Study of [68Ga]Ga-FAPI-FUSCC-II.

Fibroblast activation protein (FAP), a type II integral membrane serine protease, is a promising target for tumor diagnosis and therapy. OncoFAP has been recently discovered for PET imaging procedures for various solid malignancies. In this study, we presented the development of manual radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging. A novel series of [68Ga/177Lu]Ga/Lu-FAPI-FUSCC-I/II were produced with high radiochemical yields. [68Ga]Ga-FAPI-FUSCC-I/II and [177Lu]Lu-FAPI-FUSCC-I/II were stable in phosphate-buffered saline, fetal bovine serum, and human serum for at least 3 h. In vitro cellular uptake and blocking experiments implied that they had specificity to FAP. Additionally, the low nanomolar IC50 values of FAPI-FUSCC-II indicated that it had a high target affinity to FAP. The in vivo biodistribution and blocking study in mice bearing HT-1080-FAP tumors showed that both exhibited specific tumor uptake. [68Ga]Ga-FAPI-FUSCC-II showed a higher tumor uptake and a higher tumor/nontarget ratio than [68Ga]Ga-FAPI-FUSCC-I and [68Ga]Ga-FAPI-04. The results of ex vivo biodistribution were in accordance with the biodistribution results. Clinical [68Ga]Ga-FAPI-FUSCC-II-PET/CT imaging further demonstrated its favorable biodistribution and kinetics with elevated and reliable uptake by primary tumors (maximum standardized uptake value (SUVmax), 12.17 ± 6.67) and distant metastases (SUVmax, 9.24 ± 4.28). In summary, [68Ga]Ga-FAPI-FUSCC-II displayed increased tumor uptake and retention compared to [68Ga]Ga-FAPI-04, giving it potential as a promising tracer for the diagnostic imaging of malignant tumors with positive FAP expression.

Diagnosis and treatment of recurrent syncope in a middle-aged women.

A 50-year-old female patient, presented with repeated syncope for more than 2 years. Prior assessments were conducted at different hospitals, but no definite abnormalities were found. The patient's fear and anxiety about possible future attacks were escalating. Through a Head-up tilt test, the cause was finally identified as vasovagal syncope. Following a 5-min administration of nitroglycerin, the patient reported palpitations, nausea, and deep, rapid breathing. The electrocardiogram initially showed a first-degree atrioventricular block, progressing swiftly to a second-degree type I atrioventricular block-high atrioventricular block. Immediate intervention was undertaken, but blood pressure was not instantly ascertainable, coinciding with an abrupt loss of consciousness. Subsequent electrocardiographic findings included paroxysmal third-degree atrioventricular block, sinus arrest, and complete cardiac arrest, prompting the initiation of external cardiac compressions. The longest recorded ventricular arrest approximated 15 s, with sinus rhythm resuming post 10 s of cardiac compressions and the patient regaining consciousness. The patient underwent vagal ablation and no longer experienced syncope.

Metabolomic Analysis of Carotenoids Biosynthesis by Sphingopyxis sp. USTB-05.

Carotenoids belonging to the class of tetraterpenoids have extensive applications in medicine, food, nutrition, cosmetics, and feed. Among them, lutein and zeaxanthin can prevent macular degeneration in the elderly, which is very important for protecting vision. Here, we introduce the first metabolomic analysis of Sphingopyxis sp. USTB-05, aiming to shed light on the biosynthesis of carotenoids. Sphingopyxis sp. USTB-05 has the complete methylerythritol 4-phosphate (MEP) pathway and carotenoid biosynthesis pathway, especially involved in the bioconversion of zeaxanthin, violaxanthin, and astaxanthin. Metabolomic profiling identified seven carotenes and six xanthophylls synthesized by Sphingopyxis sp. USTB-05. Zeaxanthin, in particular, was found to be the most abundant, with a content of 37.1 µg/g dry cells. Collectively, the results presented herein greatly enhance our understanding of Sphingopyxis sp. USTB-05 in carotenoids biosynthesis, and thus further accelerate its fundamental molecular investigations and biotechnological applications.

Distribution, risk evaluation, and source allocation of cesium and strontium in surface soil in a mining city.

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.

Nrf2 and its dependent autophagy activation cooperatively counteract ferroptosis to alleviate acute liver injury.

Ferroptosis has been implicated in the pathophysiological progression of a variety of diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant response and can counteract ferroptosis by inducing autophagy and targeting genes involved in iron metabolism and glutathione (GSH) synthesis/metabolism. This study investigated how Nrf2 and autophagy interact to prevent ferroptosis in acute liver injury under sulforaphane (SFN) intervention. The results showed that SFN could activate Nrf2 signaling pathway and its downstream target genes, promote cell autophagy, and then combat ferroptosis to alleviate liver injury. After inhibiting Nrf2, the autophagy activated by SFN almost disappeared, and the anti-ferroptosis effect was greatly weakened. After inhibiting autophagy, SFN can still activate Nrf2 and its downstream target gene, but solute carrier family 7 member 11 (SLC7A11) membrane transfer and its cystine transport ability are significantly weakened, thus ultimately attenuating the anti-ferroptosis effect of SFN. Further studies showed that Nrf2-dependent autophagy activation disrupted SLC7A11 binding to S93-phosphorylated coiled-coil myosin-like BCL2-interacting protein (BECN1) and increased SLC7A11 membrane transfer to combat ferroptosis. In conclusion, Nrf2-dependent autophagy activation is essential for promoting SLC7A11 membrane localization to inhibit ferroptosis. Activation of Nrf2 not only upregulates the expression of SLC7A11, glutathione peroxidase 4 (GPX-4) and autophagy-related proteins, but also destroys the binding of SLC7A11 and BECN1 by inducing autophagy, thereby promoting SLC7A11 membrane transfer and GSH synthesis, and finally suppressing ferroptosis. However, inhibition of autophagy had no significant effect on the expression of Nrf2 and downstream genes during SFN anti-liver injury intervention.

Seasonal variation in diurnal blood pressure pattern.

AIMS: To explore the relationship between diurnal blood pressure (BP) pattern and season. METHODS: A total of 6765 eligible patients (average age 57.35 ± 15.53 years; male 51.8%; hypertensives 68.8%) from 1 October 2016 to 6 April 2022 were enrolled, who were divided into four dipper groups, dipper, non-dipper, riser, and extreme-dipper, according to the diurnal BP pattern calculated using their ambulatory BP monitoring data. The season which the patient was in was determined by the time of ambulatory BP monitoring examination. RESULTS: Among the 6765 patients, 2042 (31.18%) were grouped into dipper, 380 (5.6%) into extreme-dipper, 1498 (22.1%) into riser and 2845 (42.1%) into non-dipper. Only the dipper subjects showed age difference among seasons, with the average age significantly lower in winter. There was no seasonal difference in age for the other types. No seasonal difference was revealed in gender, BMI, hypertension or not. Diurnal BP patterns significantly differed among seasons (P < .001). Post hoc tests with Bonferroni correction indicated the significantly different diurnal BP pattern between any two seasons (P < .001), but not between spring and autumn (P = .257), and the significance of the P value was assessed at 0.008 (0.05/6) after Bonferroni correction. Multinomial logistic regression suggested season as an independent contributor to diurnal BP pattern. CONCLUSION: Diurnal BP pattern is influenced by season.

Biodegradation of Inosine and Guanosine by Bacillus paranthracis YD01.

Both inosine and guanosine are precursors of uric acid that may cause the diseases of hyperuricemia and gout in humans. Here, a promising bacterial strain for efficiently biodegrading both inosine and guanosine was successfully isolated from a healthy human intestine and identified as Bacillus paranthracis YD01 with 16S rRNA analysis. An initial amount of 49.6 mg·L-1 of inosine or 49.9 mg·L-1 of guanosine was completely removed by YD01 within 12 h, which showed that YD01 had a strong ability to biodegrade inosine and guanosine. Furthermore, the initial amount of 49.2 mg·L-1 of inosine or 49.5 mg·L-1 of guanosine was totally catalyzed by the intracellular crude enzymes of YD01 within 6 h, and the initial inosine amount of 49.6 mg·L-1 or guanosine of 49.7 mg·L-1 was biodegraded by the extracellular crude enzymes of YD01 within 9 h. Illumina Hiseq sequencing and database gene annotation were used to elucidate the genomic characteristics of B. paranthracis YD01. Purine nucleoside phosphorylase, encoded by gene 1785, gene 3933, and gene 4403, was found in the KEEG database, which played a crucial role in the biodegradation of inosine and guanosine. The results of this study provide valuable insights into the mechanisms for biodegrading inosine and guanosine using B. paranthracis YD01.

MiR-1307-5p targeting TRAF3 upregulates the MAPK/NF-κB pathway and promotes lung adenocarcinoma proliferation.

BACKGROUND: Non-small cell lung cancer (NSCLC) includes lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MicroRNA (miRNA) plays an important role in the regulation of post-transcriptional gene expression in animals and plants, especially in lung adenocarcinoma. METHODS: MiR-1307-5p is an miRNA with significant differences screened by the second generation of high-throughput sequencing in the early stage of our research group. In the current study, a series of in vitro and in vivo experiments were carried out. MiR-1307-5p mimic, miR-1307-5p inhibitor, and NC were transfected into A549 and H1299 lung adenocarcinoma cells. The correlation between miR-1307-5p and clinicopathological features in pathological samples was analyzed using a lung adenocarcinoma tissue microarray, and miR-1307-5p expression was detected by qPCR. CCK-8, EdU, colony formation, scratch test, and Transwell assays were used to observe cell proliferation and migration. Double luciferase assay, western blot, qPCR, and immunohistochemistry were employed in confirming the target relationship between miR-1307-5p and TRAF3. Western blotting was used to analyze the relationship between miR-1307-5p and the NF-κB/MAPK pathway. Finally, the effect of miR-1307-5p on tumor growth was studied using a subcutaneous tumorigenesis model in nude mice. RESULTS: Increased miR-1307-5p expression was significantly related to decreased overall survival rate of lung adenocarcinoma patients, revealing miR-1307-5p as a potential oncogene in lung adenocarcinoma. MiR-1307-5p mimic significantly promoted while miR-1307-5p inhibitor reduced the growth and proliferation of A549 and H1299 cells. MiR-1307-5p overexpression significantly enhanced the migration ability while miR-1307-5p inhibition reduced the migration ability of A549 and H1299 cells. Target binding of miR-1307-5p to TRAF3 was confirmed by double luciferase assay, western blot, qPCR, and immunohistochemistry. miR-1307-5p caused degradation of TRAF3 mRNA and protein. MiR-1307-5p targeted TRAF3 and activated the NF-κB/MAPK pathway. TRAF3 colocalized with p65 and the localization of TRAF3 and p65 changed in each treatment group. Tumor volume of the lv-miR-1307-5p group was significantly larger than that of the lv-NC group, and that of the lv-miR-1307-5p-inhibitor group was significantly smaller than that of the lv-NC group. CONCLUSION: In conclusion, miR-1307-5p targets TRAF3 and activates the NF-κB/MAPK pathway to promote proliferation in lung adenocarcinoma.

Biomimetic microfluidic chips for toxicity assessment of environmental pollutants.

Various types of pollutants widely present in environmental media, including synthetic and natural chemicals, physical pollutants such as radioactive substances, ultraviolet rays, and noise, as well as biological organisms, pose a huge threat to public health. Therefore, it is crucial to accurately and effectively explore the human physiological responses and toxicity mechanisms of pollutants to prevent diseases caused by pollutants. The emerging toxicological testing method biomimetic microfluidic chips (BMCs) exhibit great potential in environmental pollutant toxicity assessment due to their superior biomimetic properties. The BMCs are divided into cell-on-chips and organ-on-chips based on the distinctions in bionic simulation levels. Herein, we first summarize the characteristics, emergence and development history, composition and structure, and application fields of BMCs. Then, with a focus on the toxicity mechanisms of pollutants, we review the applications and advances of the BMCs in the toxicity assessment of physical, chemical, and biological pollutants, respectively, highlighting its potential and development prospects in environmental toxicology testing. Finally, the opportunities and challenges for further use of BMCs are discussed.

Anion Substitution to Suppress the Voltage Hysteresis of Na3MnTi(PO4)3 as a Cathode Material for Sodium-Ion Batteries.

The Mn-based polyanion compound Na3MnTi(PO4)3 (NMTP) with a Na superionic conductor (NASICON) structure has attracted incremental attention as a potential cathode material for sodium-ion batteries. However, the occupation of Mn2+ on Na+ vacancies usually leads to severe voltage hysteresis, which in turn results in significant capacity loss, slow Na+ diffusion kinetics, and poor cycling stability. Herein, anion-substituted compounds Na3MnTi(PO4)3-x(SiO4)x (x = 0.1, 0.2, and 0.3) are synthesized. It reveals that the SiO44- substitution could induce partial oxidation of Mn2+ to Mn3+, and the latter has a lower occupancy preference on Na+ vacancies. By the proposed charge compensation strategy, the Mn2+ occupation on Na+ vacancies can be significantly suppressed. As a result, the voltage hysteresis is substantially inhibited, and greatly improved electrochemical performance is achieved. This study offers an alternative strategy to address the voltage hysteresis associated with NMTP and other Mn-based NASICON cathode materials.

Chlorogenic acid regulates the expression of NPC1L1 and HMGCR through PXR and SREBP2 signaling pathways and their interactions with HSP90 to maintain cholesterol homeostasis.

BACKGROUND: Hypercholesterolemia is widely implicated in the etiology of coronary heart disease, stroke, and dementia. Evidence suggests that chlorogenic acid (CA) reduces the risk of cardiovascular disease. PURPOSE: The current study aims to explore the underlying molecular mechanism of CA in lowering cholesterol based on pregnane X receptor (PXR) and sterol regulatory element-binding protein 2 (SREBP2) regulatory pathways and their interactions with heat shock protein 90 (HSP90). METHODS: A hypercholesterolemic mouse model, HepG2 and Caco2 cell models, metabolomics analysis, and co-immunoprecipitation (COIP) were used to study the mechanism of CA lowering cholesterol. RESULTS: Treatment of the hypercholesterolemic mice with CA for 12 weeks significantly reduced body weight, blood lipid, hepatic lipid accumulation, and increased lipid excretion. The nuclear aggregation of PXR and SREBP2 was inhibited simultaneously. In addition, the expression of downstream target genes, including Niemann-pick C1-like 1 (NPC1L1) and 3­hydroxy-3-methylglutaryl-CoA reductase (HMGCR), was downregulated after CA administration. Furthermore, in HepG2 and Caco2 cell models, CA reduced intracellular cholesterol levels by inhibiting the nuclear translocation of PXR and SREBP2 and the expression of NPC1L1 and HMGCR. SREBP2 interacts with PXR through HSP90, and CA reduces the binding stability of SREBP2 and HSP90 and enhances the binding of PXR and HSP90, thus reducing the nuclear accumulation of SREBP2 and PXR simultaneously. Moreover, CA promoted the phosphorylation of AMP-activated protein kinase (AMPK) and its binding to SREBP2. This was not conducive to the binding of HSP90 and SREBP2 but enhanced the binding of HSP90 and PXR, thereby inhibiting the nuclear translocation of SREBP2 and PXR and reducing intracellular cholesterol levels. However, no noticeable direct binding between AMPK and PXR was observed. CONCLUSION: CA downregulates NPC1L1 and HMGCR expression by acting on the AMPK/SREBP2 direct pathway and the AMPK/SREBP2/HSP90/PXR indirect pathway, thus retaining cholesterol homeostasis.

The combination of high-frequency QRS and ST-segment alterations during exercise stress tests enhanced the diagnostic efficacy for coronary artery disease.

BACKGROUND: High-frequency QRS (HF-QRS) manifests as a novel adjunct electrocardiographic marker with potential utility in coronary artery disease (CAD) detection. HYPOTHESIS: We hypothesize that HF-QRS analysis may be superior to conventional ST-segment analysis in detecting CAD, and the combination of these two analyses in the exercise stress test may enhance the diagnostic efficacy for CAD. METHODS: The study incorporated a sample of 157 patients (mean age 62 ± $\pm $ 9 years) referred for nonemergent angiography. Before angiography, patients underwent exercise stress testing utilizing an upright bicycle. High-resolution electrocardiogram (ECG) data were collected during the exercise test, facilitating both HF-QRS and conventional ST-segment analyses. The diagnostic efficacy of HF-QRS and ST-segment analysis were compared, utilizing angiographic outcomes as the gold standard. The study design integrated HF-QRS analysis and ST-segment analysis via sequential and concurrent testing protocols. RESULTS: In terms of CAD detection, HF-QRS analysis displayed superior sensitivity compared to conventional ST-segment analysis (63% vs. 37%, p = .002). The serial test significantly increased specificity from 79% to 97% (p = .002) compared to ST-deviation analysis alone. It showed a markedly low sensitivity of 26%. The parallel test significantly increased sensitivity from 37% to 77% (p < .001), while retaining a moderate level of specificity of 51%. The quantity of ECG leads exhibiting a positive HF-QRS response demonstrated a correlation with the severity of CAD (p < .001). CONCLUSIONS: HF-QRS analysis exhibited superior sensitivity in detecting angiographically confirmed CAD relative to conventional ST-segment analysis. Moreover, the combination of HF-QRS and ST-segment alterations during exercise stress test enhanced the diagnostic efficacy for CAD.

Photocurable and Temperature-Sensitive Bioadhesive Hydrogels for Sutureless Sealing of Full-Thickness Corneal Wounds.

Penetrating corneal wounds can cause severe vision impairment and require prompt intervention to restore globe integrity and minimize the risk of infection. Tissue adhesives have emerged as a promising alternative to suturing for mitigating postoperative complications. However, conventional water-soluble adhesives suffer formidable challenges in sealing penetrating corneal wounds due to dilution or loss in a moist environment. Inspired by the robust adhesion of mussels in aquatic conditions, an injectable photocurable bioadhesive hydrogel (referred to as F20HD5) composed of polyether F127 diacrylate and dopamine-modified hyaluronic acid methacrylate is developed for sutureless closure of corneal full-thickness wounds. F20HD5 exhibits high transparency, wound-sealing ability, proper viscosity, biodegradability, and excellent biocompatibility. It allows in situ cross-linking via visible light, thereby providing sufficient mechanical strength and adhesiveness. In vivo, the adhesive hydrogel effectively closed penetrating linear corneal incisions and corneal injuries with minimal tissue loss in rabbits. During the 56-day follow-up, the hydrogel facilitates the repair of the injured corneas, resulting in more symmetrical curvatures and less scarring in distinction to the untreated control. Thus, bioinspired hydrogel holds promise as an effective adhesive for sealing full-thickness corneal wounds.

Enzymatic mechanism of MlrB for catalyzing linearized microcystins by Sphingopyxis sp. USTB-05.

Microcystins (MCs) are the most widespread cyanobacterial toxins in eutrophic water body. As high toxic intermediate metabolites, linearized MCs are further catalyzed by linearized microcystinase (MlrB) of Sphingopyxis sp. USTB-05. Here MlrB structure was studied by comprizing with a model representative of the penicillin-recognizing enzyme family via homology modeling. The key active sites of MlrB were predicted by molecular docking, and further verified by site-directed mutagenesis. A comprehensive enzymatic mechanism for linearized MCs biodegradation by MlrB was proposed: S77 transferred a proton to H307 to promote a nucleophilic attack on the peptide bond (Ala-Leu in MC-LR or Ala-Arg in MC-RR) of linearized MCs to form the amide intermediate. Then water was involved to break the peptide bond and produced the tetrapeptide as product. Meanwhile, four amino acid residues (K80, Y171, N173 and D245) acted synergistically to stabilize the substrate and intermediate transition states. This study firstly revealed the enzymatic mechanism of MlrB for biodegrading linearized MCs with both computer simulation and experimental verification.

Head-to-head comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT for the evaluation of tonsil cancer and lymph node metastases: a single-centre retrospective study.

BACKGROUND: This study aimed to compare the diagnostic value of [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT imaging for primary lesions and metastatic lymph nodes in patients with tonsil cancer. METHOD: Twenty-one tonsil cancer patients who underwent [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT scans within two weeks in our centre were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of the two tracers were compared by using the Mann‒Whitney U test. In addition, the sensitivity, specificity, and accuracy of the two methods for diagnosing metastatic lymph nodes were analysed. RESULTS: In detecting primary lesions, the efficiency was higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (20/22) than for [18F]FDG PET/CT (9/22). Although [68 Ga]Ga-DOTA-FAPI-04 uptake (SUVmax, 5.03 ± 4.06) was lower than [18F]FDG uptake (SUVmax, 7.90 ± 4.84, P = 0.006), [68 Ga]Ga-DOTA-FAPI-04 improved the distinction between the primary tumor and contralateral normal tonsillar tissue. The TBR was significantly higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (3.19 ± 2.06) than for [18F]FDG PET/CT (1.89 ± 1.80) (p < 0.001). In lymph node analysis, SUVmax and TBR were not significantly different between [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT (7.67 ± 5.88 vs. 8.36 ± 6.15, P = 0.498 and 5.56 ± 4.02 vs. 4.26 ± 3.16, P = 0.123, respectively). The specificity and accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT were higher than those of [18F]FDG PET/CT in diagnosing metastatic cervical lymph nodes (all P < 0.05). CONCLUSION: The availability of [68 Ga]Ga-DOTA-FAPI-04 complements the diagnostic results of [18F]FDG by improving the detection rate of primary lesions and the diagnostic accuracy of cervical metastatic lymph nodes in tonsil cancer compared to [18F]FDG.

Imaging of Tumor Stroma Using 68Ga-FAPI PET/CT to Improve Diagnostic Accuracy of Primary Tumors in Head and Neck Cancer of Unknown Primary: A Comparative Imaging Trial.

The low detection rate of primary tumors by current diagnostic techniques remains a major concern for patients with head and neck cancer of unknown primary (HNCUP). Therefore, in this study, we aimed to investigate the potential role of 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT compared with 18F-FDG PET/CT for the detection of primary tumors of HNCUP. Methods: In this prospective comparative imaging trial conducted at Fudan University Shanghai Cancer Center, 91 patients with negative or equivocal findings of a primary tumor by comprehensive clinical examination and conventional imaging were enrolled from June 2020 to September 2022. The presence of a primary tumor was recorded by 3 experienced nuclear medicine physicians. Primary lesions were validated by histopathologic analysis and a composite reference standard. Results: Of the 91 patients (18 women, 73 men; median age, 60 y; age range, 24-76 y), primary tumors were detected in 46 (51%) patients after a thorough diagnostic work-up. 68Ga-FAPI PET/CT detected more primary lesions than 18F-FDG PET/CT (46 vs. 17, P < 0.001) and showed better sensitivity, positive predictive value, and accuracy in locating primary tumors (51% vs. 25%, 98% vs. 43%, and 51% vs. 19%, respectively). Furthermore, 68Ga-FAPI PET/CT led to treatment changes in 22 of 91 (24%) patients compared with 18F-FDG PET/CT. The Kaplan-Meier curve illustrated that patients with unidentified primary tumors had a significantly worse prognosis than patients with identified primary tumors (hazard ratio, 5.77; 95% CI, 1.86-17.94; P = 0.0097). Conclusion: 68Ga-FAPI PET/CT outperforms 18F-FDG PET/CT in detecting primary lesions and could serve as a sensitive, reliable, and reproducible imaging modality for HNCUP patients.

Engineered Mesenchymal Stromal Cell Exosomes-Loaded Microneedles Improve Corneal Healing after Chemical Injury.

Corneal alkali burns represent a prevalent ophthalmic emergency with the potential to induce blindness. The main contributing mechanisms include excessive inflammation and delayed wound healing. Existing clinical therapies have limitations, promoting the exploration of alternative methods that offer improved efficacy and reduced side effects. Adipose-derived stem cell-exosome (ADSC-Exo) has the potential to sustain immune homeostasis and facilitate tissue regeneration. Nevertheless, natural ADSC-Exo lacks disease specificity and exhibits limited bioavailability on the ocular surface. In this study, we conjugated antitumor necrosis factor-α antibodies (aT) to the surface of ADSC-Exo using matrix metalloproteinase-cleavable peptide chains to create engineered aT-Exo with synergistic effects. In both in vivo and in vitro assessments, aT-Exo demonstrated superior efficacy in mitigating corneal injuries compared to aT alone, unmodified exosomes, or aT simply mixed with exosomes. The cleavable conjugation of aT-Exo notably enhanced wound healing and alleviated inflammation more effectively. Simultaneously, we developed poly(vinyl alcohol) microneedles (MNs) for precise and sustained exosome delivery. The in vivo results showcased the superior therapeutic efficiency of MNs compared with conventional topical administration and subconjunctival injection. Therefore, the bioactive nanodrugs-loaded MNs treatment presents a promising strategy for addressing ocular surface diseases.

PRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury.

Excessive host immune responses contribute to severe malaria with high mortality. Here, we show that PRL2 in innate immune cells is highly related to experimental malaria disease progression, especially the development of murine severe malaria. In the absence of PRL2 in myeloid cells, Plasmodium berghei infection results in augmented lung injury, leading to significantly increased mortality. Intravital imaging revealed greater neutrophilic inflammation and NET formation in the lungs of PRL2 myeloid conditional knockout mice. Depletion of neutrophils prior to the onset of severe disease protected mice from NETs associated lung injury, and eliminated the difference between WT and PRL2 CKO mice. PRL2 regulates neutrophil activation and NET accumulation via the Rac-ROS pathway, thus contributing to NETs associated ALI. Hydroxychloroquine, an inhibitor of PRL2 degradation alleviates NETs associated tissue damage in vivo. Our findings suggest that PRL2 serves as an indicator of progression to severe malaria and ALI. In addition, our study indicated the importance of PRL2 in NET formation and tissue injury. It might open a promising path for adjunctive treatment of NET-associated disease.

Spectral shifts and spectral switches produced by the scattering system of two anisotropic particles in different distance.

We investigate the scattering of polychromatic plane light wave incident upon a system formed with two anisotropic particles in different distance. The analytical expression for the spectrum of the scattered field is derived. Numerical examples show the phenomena of spectral shifts and spectral switches of the scattered field. The influences of the scattering direction and the difference of the particles on the spectral switch are illustrated.

Importance of secondary decomposition in the accurate prediction of daily-scale ozone pollution by machine learning.

Machine learning (ML) models have been proven as a reliable tool in predicting ambient pollution concentrations at various places in the world. However, their performance in predicting the maximum daily 8-h averaged ozone (MDA8 O3), the metric often used for O3 pollution assessment and management, is relatively poorer. This is largely resulted from more irregular data fluctuations of the MDA8 O3 levels governed collectively by the synoptic condition, local photochemistry, and long-range transport. In order to improve the prediction accuracy of MDA8 O3, this study developed a secondary decomposition ML model framework which coupled the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) as the primary decomposition, the variational mode decomposition (VMD) as secondary decomposition, and the gate recurrent unit (GRU) ML model. By applying this secondary decomposition model framework on MDA8 O3 prediction for the first time, we showed that the prediction accuracy of MDA8 O3 is largely improved from R2 of 0.46 and RMSE of 30.4 µg/m3 for GRU without decomposition to R2 of 0.91 and RMSE of 12.6 µg/m3 over the Pearl River Delta of China. We also found that the prediction accuracy rate of O3 pollution non-attainments, an essential indicator for initiating contingency O3 pollution control, improved greatly from 14.9 % for GRU without decomposition to 72.5 %. The performance of O3 pollution non-attainment prediction is relatively higher in southwestern PRD, which is mainly due to greater number and severity of O3 non-attainments in southwestern cities located downwind of the emission hotspot area at central PRD. This study underscored the importance of secondary decomposition in accurately predicting daily-scale O3 concentration and non-attainments over the PRD, which can be extended to other photochemically active region worldwide to improve their O3 prediction accuracy and assist in O3 contingency control.