Enhanced Detection of Early Pulmonary Fibrosis Disease Using 68Ga-FAPI-LM3 PET.

Early detection of pulmonary fibrosis is a critical yet insufficiently met clinical necessity. This study evaluated the effectiveness of FAPI-LM3, a 68Ga-radiolabeled heterobivalent molecular probe that targets fibroblast activating protein (FAP) and somatostatin receptor 2 (SSTR2), in the early detection of pulmonary fibrosis, leveraging its potential for early disease identification. A bleomycin-induced early pulmonary fibrosis model was established in C57BL/6 mice for 7 days. FAP and SSTR2 expression levels were quantitatively assessed in human idiopathic pulmonary fibrosis lung tissue samples and bleomycin-treated mouse lung tissues by using western blotting, real-time quantitative PCR (RT-qPCR), and immunofluorescence techniques. The diagnostic performance of FAPI-LM3 was investigated by synthesizing monomeric radiotracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3 alongside the heterobivalent probe 68Ga-FAPI-LM3. These imaging radiopharmaceuticals were used in small-animal PET to compare their uptake in fibrotic and normal lung tissues. Results indicated significant upregulation of FAP and SSTR2 at both RNA and protein levels in fibrotic lung tissues compared with that in normal controls. PET imaging demonstrated significantly enhanced uptake of the 68Ga-FAPI-LM3 probe in fibrotic lung tissues, with superior visual effects compared to monomeric tracers. At 60 min postinjection, early stage fibrotic tissues (day 7) demonstrated low-to-medium uptake of monomeric probes, including 68Ga-DOTA-LM3 (0.45 ± 0.04% ID/g) and 68Ga-FAPI-46 (0.78 ± 0.09% ID/g), whereas the uptake of the heterobivalent probe 68Ga-FAPI-LM3 (1.90 ± 0.10% ID/g) was significantly higher in fibrotic lesions than in normal lung tissue. Blockade experiments confirmed the specificity of 68Ga-FAPI-LM3 uptake, which was attributed to synergistic targeting of FAP and SSTR2. This study demonstrates the potential of 68Ga-FAPI-LM3 for early pulmonary fibrosis detection via molecular imaging, offering significant benefits over monomeric tracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3. This strategy offers new possibilities for noninvasive and precise early detection of pulmonary fibrosis.

Effect and mechanism of Yiqing decoction on hyperuricemia rats.

This study aimed to experimentally compare the uric acid-lowering effect and renal protection of Yiqing Fang in a rat model of hyperuricemia. Additionally, we used network pharmacology to predict the potential active components, targets, and pathways of Yiqing Fang. Male SD rats were randomly divided into control, model, Yiqing Fang, allopurinol, and probenecid groups. Serum creatinine (Scr), blood urea nitrogen (BUN), serum uric acid (UA), alanine transaminase (ALT), complete blood count, and urinary NAG enzyme levels were measured. Standard pathology and electron microscopy samples were prepared from the left kidney to observe renal pathological changes, renal fibrosis, and collagen III expression levels. In addition, we employed network pharmacology to investigate the molecular mechanisms and pathways of Yiqing Fang. The Yiqing Fang group showed significantly lower levels of Scr, BUN, UA, ALT, urinary NAG enzyme, complete blood count, and liver function tests compared to the model group (P < 0.05). Furthermore, both the Yiqing Fang and allopurinol groups exhibited significant reductions in renal pathological changes compared to the model group, along with decreased expression of collagen III. Network pharmacology analysis identified a total of 27 specific sites related to hyperuricemia. The main active components were predicted to include quercetin, berberine, beta-sitosterol, epimedin C, and dioscin. The primary target sites were predicted to include TNF, IL-6, IL-17, IL-1B, and VEGFA. Yiqing Fang may exert its effects through regulation of drug response, urate metabolism, purine compound absorption, inflammation response, lipopolysaccharide response, cytokine activity, and antioxidant activity. These effects may be mediated through signaling pathways such as IL-17, HIF-1, and AGE-RAGE. Yiqing Fang offers potential as a treatment for hyperuricemia due to its multiple active components, targeting of various sites, and engagement of multiple pathways.

Spatial and temporal distribution characteristics and risk assessment of heavy metals in groundwater of Pingshuo mining area.

Groundwater pollution in the Pingshuo mining area is strongly associated with mining activities, with heavy metals (HMs) representing predominant pollutants. To obtain accurate information about the pollution status and health risks of groundwater, 189 groups of samples were collected from four types of groundwater, during three periods of the year, and analyzed for HMs. The results showed that the concentration of HMs in groundwater was higher near the open pit, waste slag pile, riverfront area, and human settlements. Except for Ordovician groundwater, excessive HMs were found in all investigated groundwater of the mining area, as compared with the standard thresholds. Fe exceeded the threshold in 13-75% of the groundwater samples. Three sources of HMs were identified and quantified by Pearson's correlation analysis and the PMF model, including coal mining activities (68.22%), industrial, agricultural, and residential chemicals residue and leakage (16.91%), and natural sources (14.87%). The Nemerow pollution index revealed that 7.58% and 100% of Quaternary groundwater and mine water samples were polluted. The health risk index for HMs in groundwater showed that the non-carcinogenic health risk ranged from 0.18 to 0.42 for adults, indicating an acceptable level. Additionally, high carcinogenic risks were identified in Quaternary groundwater (95.45%), coal series groundwater (91.67%), and Ordovician groundwater (26.67%). Both carcinogenic and non-carcinogenic risks were greater for children than adults, highlighting their increased vulnerability to HMs in groundwater. This study provides a scientific foundation for managing groundwater quality and ensuring drinking water safety in mining areas.

Global Phylogeography and Genomic Epidemiology of Carbapenem-Resistant blaOXA-232-Carrying Klebsiella pneumoniae Sequence Type 15 Lineage.

Prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has compromised antimicrobial efficacy against severe infections worldwide. To monitor global spread, we conducted a comprehensive genomic epidemiologic study comparing sequences from 21 blaOXA-232-carrying CRKP isolates from China with K. pneumoniae sequence type (ST) 15 strains from 68 countries available in GenBank. Phylogenetic and phylogeographic analyses revealed all blaOXA-232-carrying CRKP isolates belonged to ST15 lineage and exhibited multidrug resistance. Analysis grouped 330 global blaOXA-232-carrying ST15 CRKP strains into 5 clades, indicating clonal transmission with small genetic distances among multiple strains. The lineage originated in the United States, then spread to Europe, Asia, Oceania, and Africa. Most recent common ancestor was traced back to 2000; mutations averaged ≈1.7 per year per genome. Our research helps identify key forces driving global spread of blaOXA-232-carrying CRKP ST15 lineage and emphasizes the importance of ongoing surveillance of epidemic CRKP.

The Effect of ß-Lactam Antibiotics on the Evolution of Ceftazidime/Avibactam and Cefiderocol Resistance in KPC-Producing Klebsiella pneumoniae.

In this study, we aimed to clarify the evolutionary trajectory of a Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) population during ß-lactam antibiotic therapy. Five KPC-Kp isolates were collected from a single patient. Whole-genome sequencing and a comparative genomics analysis were performed on the isolates and all blaKPC-2-containing plasmids to predict the population evolution process. Growth competition and experimental evolution assays were conducted to reconstruct the evolutionary trajectory of the KPC-Kp population in vitro. Five KPC-Kp isolates (KPJCL-1 to KPJCL-5) were highly homologous, and all harbor an IncFII blaKPC-containing plasmid (pJCL-1 to pJCL-5). Although the genetic structures of these plasmids were almost identical, distinct copy numbers of the blaKPC-2 gene were detected. A single copy of blaKPC-2 was presented in pJCL-1, pJCL-2, and pJCL-5, two copies of blaKPC (blaKPC-2 and blaKPC-33) were presented in pJCL-3, and three copies of blaKPC-2 were presented in pJCL-4. The blaKPC-33-harboring KPJCL-3 isolate presented resistance to ceftazidime-avibactam and cefiderocol. The blaKPC-2 multicopy strain KPJCL-4 had an elevated ceftazidime-avibactam MIC. The patient had been exposed to ceftazidime, meropenem, and moxalactam, after which KPJCL-3 and KPJCL-4 were isolated, which both showed a significant competitive advantage under antimicrobial pressure in vitro. Experimental evolution assays revealed that blaKPC-2 multicopy-containing cells were increased in the original single-copy blaKPC-2-harboring KPJCL-2 population under selection with ceftazidime, meropenem, or moxalactam, generating a low-level ceftazidime-avibactam resistance phenotype. Moreover, blaKPC-2 mutants with a G532T substitution, G820 to C825 duplication, G532A substitution, G721 to G726 deletion, and A802 to C816 duplication increased in the blaKPC-2 multicopy-containing KPJCL-4 population, generating high-level ceftazidime-avibactam resistance and reduced cefiderocol susceptibility. Ceftazidime-avibactam and cefiderocol resistance can be selected by ß-lactam antibiotics other than ceftazidime-avibactam. Notably, blaKPC-2 gene amplification and mutation are important in KPC-Kp evolution under antibiotic selection.

The Interaction between Tegument Proteins ORF33 and ORF45 Plays an Essential Role in Cytoplasmic Virion Maturation of a Gammaherpesvirus.

Tegument, which occupies the space between the nucleocapsid and the envelope, is a unique structure of a herpesvirion. Tegument proteins are major components of tegument and play critical roles in virus life cycle. Murine gammaherpesvirus 68 (MHV-68), a member of the gammaherpesvirus subfamily, is closely related to two human herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). We have previously shown that MHV-68 ORF33, conserved among all herpesviruses, encodes a tegument protein that is associated with intranuclear capsids and is essential for virion morphogenesis and egress. Another tegument protein ORF45, which is conserved only among gammaherpesviruses, also plays an essential role in virion morphogenesis of MHV-68. In this study, we investigated the underlying mechanism and showed that these two proteins colocalize and interact with each other during virus infection. We mapped the ORF33-interacting domain to the conserved carboxyl-terminal 23 amino acids (C23) of ORF45. Deletion of the C23 coding sequence in the context of viral genome abolished the production of infectious virions. Transmission electron microscopy results demonstrated that C23 of ORF45 are essential for virion tegumentation in the cytoplasm. We further mapped the ORF45-interacting domain to the N-terminal 17 amino acids (N17) of ORF33. Deletion of the N17 coding sequence in the context of viral genome also abolished production of infectious virions, and N17 of ORF33 are also essential for virion tegumentation in the cytoplasm. Taken together, our data strongly indicate that the interaction between ORF45 and ORF33 plays an essential role in cytoplasmic maturation of MHV-68 virions. IMPORTANCE A critical step in viral lytic replication is the assembly of progeny viral particles. Herpesviruses are important pathogens. A herpesvirus particle comprises, from inside to outside, four layers: DNA core, capsid, tegument, and envelope. The tegument layer contains dozens of virally encoded tegument proteins, which play critical roles in virus assembly. Murine gammaherpesvirus 68 (MHV-68) is a tumor-associated herpesvirus and is closely related to Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus. We previously found that the absence of either tegument protein ORF33 or ORF45 inhibits the translocation of nucleocapsids to the cytoplasm and blocks virion maturation, but the underlying mechanism remained unclear. Here, we showed that ORF33 interacts with ORF45. We mapped their interaction domains and constructed viral mutants with defects in ORF33-ORF45 interaction. Transmission electron microscopy data demonstrated that the assembly of these viral mutants in the cytoplasm is blocked. Our results indicate that ORF33-ORF45 interaction is essential for gammaherpesvirus replication.

Prognostic value of fibroblast activation protein expressing tumor volume calculated from [68 Ga]Ga-FAPI PET/CT in patients with esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to investigate the prognostic value of semiquantitative parameters derived from [68 Ga]Ga-fibroblast activation protein inhibitor (FAPI) PET/CT for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. METHODS: We conducted a retrospective analysis on patients from a prospective parent study (NCT04416165). A total of 45 patients with locally advanced ESCC who underwent [68 Ga]Ga-FAPI from December 2019 to March 2021 were included. The maximum standard uptake value (SUVmax), gross tumor volume (GTV), and total lesion-FAPI (TL-FAPI) of the primary tumor were calculated from the corresponding PET/CT image. Unpaired parameters were compared using Student's t test or the Mann-Whitney U test. Paired parameters were compared using the paired t test or the Wilcoxon matched-pairs signed-rank test. Kaplan-Meier curves were generated to calculate progression-free survival (PFS) and overall survival (OS) rates, and Cox regression analysis was performed to determine which PET/CT parameters were prognostic factors for PFS and/or OS. RESULTS: Thirty-four of the 45 patients met the criteria, and the median follow-up time was 24 months (16-29 months). SUVmax-FAPI, GTVFAPI, and TL-FAPI in patients with stage T4 tumors were significantly higher than those in patients with stage T2/T3 tumors (all P < 0.01). In the univariate Cox regression analysis, T stage, N stage, GTVFAPI, and TL-FAPI were associated with PFS, and T stage, GTVFAPI, and TL-FAPI were associated with OS. Upon multivariable analysis, GTVFAPI was an independent prognostic factor for both PFS (hazard ratio (HR), 5.76; 95% confidence interval (CI), 2.13-15.57, P = 0.001) and OS (HR, 4.96; 95% CI, 2.55-18.79, P = 0.001). CONCLUSION: This pilot study revealed that [68 Ga]Ga-FAPI PET/CT may have prognostic value for patients with ESCC treated with definitive chemoradiotherapy. It may aid in personalized patient management by steering treatment modifications before therapy. Prospective studies with larger samples and longer observation periods are needed.

Comparison of [68Ga]Ga-FAPI and [18F]FDG uptake in patients with gastric signet-ring-cell carcinoma: a multicenter retrospective study.

OBJECTIVE: In this study, we investigated the role of [68Ga]Ga-FAPI PET imaging in the detection of primary and metastatic gastric signet-ring-cell carcinoma (GSRCC) and compared with [18F]FDG PET. METHODS: This retrospective multicenter analysis included 34 patients with histologically confirmed GSRCCs from four medical centers. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. [18F]FDG and [68Ga]Ga-FAPI uptakes were compared by using the Wilcoxon signed-rank test. McNemar's test was used to compare the diagnostic accuracy between the two techniques. RESULTS: Data were analyzed from 27 paired PET/CT and 7 paired PET/MRI scans for 34 GSRCC patients (16 men and 18 women) who had a median age of 51 years (range: 25-85 years). [68Ga]Ga-FAPI PET showed higher SUVmax and TBR values than did [18F]FDG PET in the primary tumors (SUVmax: 5.2 vs. 2.2, p = 0.001; TBR: 7.6 vs. 1.3, p < 0.001), involved lymph nodes (SUVmax: 6.8 vs. 2.5, p < 0.001; TBR: 5.8 vs. 1.3, p < 0.001), and bone and visceral metastases (SUVmax: 6.5 vs. 2.4, p < 0.001; TBR: 6.3 vs. 1.3, p < 0.001). In diagnostic performance, [68Ga]Ga-FAPI PET exhibited higher sensitivity than [18F]FDG PET for detecting primary tumors (73% [16/22] vs. 18% [4/22], p < 0.001), local recurrences (100% [7/7] vs. 29% [2/7], p = 0.071), lymph node metastases (77% [59/77] vs. 23% [18/77], p < 0.001), and distant metastases (93% [207/222] vs. 39% [86/222], p < 0.001). CONCLUSION: The results from this multicenter retrospective analysis justify the clinical use of [68Ga]Ga-FAPI tracers for GSRCC diagnosis and staging. KEY POINTS: • [68Ga]Ga-FAPI PET/CT is a promising imaging modality for the detection of primary and metastatic disease and has implications for TNM staging in GSRCC. • In this multicenter study of 34 patients with GSRCC, [68Ga]Ga-FAPI PET exhibited greater radiotracer uptake, tumor-to-background ratios, and diagnostic accuracy than [18F]FDG PET for detecting primary/recurrent tumors and metastatic lesions.

TBK1-medicated DRP1 phosphorylation orchestrates mitochondrial dynamics and autophagy activation in osteoarthritis.

Mitochondrial dynamics, including mitochondrial fission and fusion, are critical for maintaining mitochondrial functions. Evidence shows that TANK-binding kinase 1 (TBK1) regulates mitochondrial fusion and fission and then mitophagy. Since a previous study demonstrates a strong correlation between mitophagy and osteoarthritis (OA), we herein investigated the potential role of TBK1 in OA process and mitochondrial functions. We demonstrated a strong correlation between TBK1 and OA, evidenced by significantly downregulated expression of TBK1 in cartilage tissue samples of OA patients and in the chondrocytes of aged mice, as well as TNF-α-stimulated phosphorylation of TBK1 in primary mouse chondrocytes. TBK1 overexpression significantly attenuated TNF-α-induced apoptosis and abnormal mitochondrial function in primary mouse chondrocytes. Furthermore, TBK1 overexpression induced remodeling of mitochondrial morphology by directly phosphorylating dynamin-related protein 1 (DRP1) at Ser637, abolishing the fission of DRP1 and preventing its fragmentation function. Moreover, TBK1 recruitment and DRP1 phosphorylation at Ser637 was necessary for engulfing damaged mitochondria by autophagosomal membranes during mitophagy. Moreover, we demonstrated that APMK/ULK1 signaling contributed to TBK1 activation. In OA mouse models established by surgical destabilization of the medial meniscus, intraarticular injection of lentivirus-TBK1 significantly ameliorated cartilage degradation via regulation of autophagy and alleviation of cell apoptosis. In conclusion, our results suggest that the TBK1/DRP1 pathway is involved in OA and pharmacological targeting of the TBK1-DRP1 cascade provides prospective therapeutic benefits for the treatment of OA.

Temporal dynamics of soil dissolved organic carbon in temperate forest managed by prescribed burning in Northeast China.

Dissolved organic carbon (DOC) is an important function of soil organic carbon and sensitive to environmental disturbance. Few studies have explored the variations in soil DOC dynamics and effects on soil physicochemical properties following prescribed burnings. In this study, Pinus koraiensis plantation forests in Northeast China were selected and subjected to prescribed burning in early November 2018. Soil DOC and different soil physicochemical and biological properties in the 0-10 cm and 10-20 cm soil layers were sampled six times within two years after a prescribed burning. In this study, some soil physicochemical (SOC, TN, and ST) and microbial biomass properties (MBC) recovered within two years after a prescribed burning. Compared to the unburned control stands, the post-fire soil DOC concentrations in the upper and lower soil layers increased by 16% and 12%, respectively. Soil DOC concentrations varied with sampling time, and peaked one year after the prescribed burning. Our results showed that soil chemical properties (NH4+-N and pH) rather than biological properties (microbial biomass) were the main driving factors for changes in post-fire soil DOC concentrations. Current study provides an important reference for post-fire and seasonal soil C cycling in plantation forests of Northeast China.

Effects of wildfire disturbance on forest soil microbes and colonization of ericoid mycorrhizal fungi in northern China.

Wildfires affect forest succession and restoration by changing the community structure of soil microorganisms. Mycorrhizal formation is essential for plant growth and development. However, the driving mechanism of their natural succession after wildfire is still unclear. In this study, we examined the community structure of soil bacteria and fungi along a time series of natural recovery after wildfires in the Greater Khingan Range of China (2020 fires, 2017 fires, 2012 fires, 2004 fires, 1991 fires, and unburned). By exploring the effects of wildfire on plant traits, fruit nutrition, colonization of mycorrhizal fungi and its influencing mechanism. The results show that natural succession after wildfires significantly changed the community composition of bacteria and fungi, with ß diversity having a greater impact but less impact on the α diversity of microorganisms. Wildfires significantly changed plant traits and fruit nutrient content. The changes in colonization rate and customization intensity of mycorrhizal fungi were caused by increased MDA content and soluble sugar content and increased MADS-box gene and DREB1 gene expression in lingonberry (Vaccinium vitis-idaea L.). Our results showed that the soil bacterial and fungal communities in the boreal forest ecosystem changed significantly during wildfire recovery and changed the colonization rate of lingonberry mycorrhizal fungi. This study provides a theoretical basis for the restoration of forest ecosystems after wildfires.

DIC measurement method for large rotation based on improved grid-based motion statistics.

As a noncontact optical measurement method, the digital image correlation (DIC) method can provide full-field displacement and strain measurement during object deformation. In the case of small rotation deformation, the traditional DIC method can obtain accurate deformation measurement results. However, when the object rotates at a large angle, the traditional DIC method cannot obtain the extreme value of the correlation function, resulting in the occurrence of decorrelation. In order to address the issue, a full-field deformation measurement DIC method based on improved grid-based motion statistics is proposed for large rotation angles. First, the speeded up robust features algorithm is applied to extract and match the feature point pairs between the reference image and the deformed image. Furthermore, an improved grid-based motion statistics algorithm is proposed to eliminate the wrong matching point pairs. Then, the deformation parameters of the feature point pairs obtained by the affine transformation are taken as the initial deformation value for DIC calculation. Finally, the intelligent gray-wolf optimization algorithm is used to obtain the accurate displacement field. The effectiveness of the proposed method is proved by simulation and practical experiments, and the comparative experiments show that the proposed method is faster and more robust.

The Relationship Between GNRI Changes and Bone Metabolism Parameters and the Occurrence of Osteoporosis in Elderly Male Patients with T2D.

Background: Type 2 diabetes (T2D) and osteoporosis are both diseases with a high clinical incidence. Among the population with diabetes, T2D accounts for approximately 90%. With the change in people's eating habits and lifestyles, the incidence rate is gradually increasing. Aim: We aimed to explore the relationship between the change in the Geriatric Nutritional Risk Index (GNRI) and the change in bone metabolism index parameters in elderly male patients with T2D and the occurrence of osteoporosis. Methods: A total of 290 elderly male patients with type 2 diabetes (T2D) diagnosed in North China University of Science and Technology Affiliated Hospital from October 2019 to February 2022 were selected for GNRI evaluation. Of these patients, 148 with a GNRI > 98 (the normal group) and 142 with a GNRI ≤ 98 (the risk group) were selected for the study. The levels of 1,25-hydroxyvitamin D3 [1,25 (OH) 2D3], type 1 collagen N-terminal propeptide (P1NP), serum type 1 collagen C-terminal peptide hinge (S-CTX), osteocalcin (OC) and serum bone alkaline phosphatase (BALP) in the 2 groups were detected and compared. A dual-energy bone mineral density instrument was used to detect the bone mineral density (BMD) in the 2 groups. The logistic regression model was used to analyze the relationship between the occurrence of osteoporosis and indicators such as GNRI, and the receiver operating characteristic (ROC) curve was drawn to analyze the value of GNRI in predicting osteoporosis in elderly patients with T2D. Results: The 1,25(OH)2D3 and P1NP levels in the risk group were lower than in the normal group, and the serum S-CTX and BALP levels in the risk group were higher than in the normal group; the differences were statistically significant (P <.05). The average BMD values of femoral neck, femur trochanter, Ward triangle and lumbar spine in the risk group were lower than in the normal group; the differences were statistically significant (P < .05). There were 70 patients with osteoporosis in the risk group and 9 patients with osteoporosis in the normal group. The difference in the detection rate of osteoporosis between the 2 groups was statistically significant (χ2 = 68.281; P = .000 < .05). The area under the curve (AUC) value under the ROC curve predicted by the GNRI for osteoporosis in elderly patients with T2D was 0.719, the sensitivity was 51.43% and the specificity was 97.26%. The logistic regression model showed that duration of diabetes, glycated hemoglobin A1c (HbA1c), S-CTX and BALP were independent risk factors for osteoporosis in elderly male patients with T2D (P < .05). Increased 1,25(OH)2D3, ALB and GNRI can reduce the risk for osteoporosis in elderly male patients with T2D (P < .05). Conclusion: GNRI can reflect the nutritional status of elderly male patients with T2D, which is related to some extent to osteoporosis caused by loss of bone mass.

Enantioselective effects of chiral prothioconazole and its metabolites: Oxidative stress in HepG2 cells and lysozyme activity.

Chiral pesticides may exhibit enantioselectivity in terms of bioconcentration, environmental fate, and reproductive toxicity. Here, chiral prothioconazole and its metabolites were selected to thoroughly investigate their enantioselective toxicity and mechanisms at the molecular and cellular levels. Multispectral techniques revealed that the interaction between chiral PTC/PTCD and lysozyme resulted in the formation of a complex, leading to a change in the conformation of lysozyme. Meanwhile, the effect of different conformations of PTC/PTCD on the conformation of lysozyme differed, and its metabolites were able to exert a greater effect on lysozyme compared to prothioconazole. Moreover, the S-configuration of PTCD interacted most strongly with lysozyme. This conclusion was further verified by DFT calculations and molecular docking as well. Furthermore, the oxidative stress indicators within HepG2 cells were also affected by chiral prothioconazole and its metabolites. Specifically, S-PTCD induced more substantial perturbation of the normal oxidative stress processes in HepG2 cells, and the magnitude of the perturbation varied significantly among different configurations (P > 0.05). Overall, chiral prothioconazole and its metabolites exhibit enantioselective effects on lysozyme conformation and oxidative stress processes in HepG2 cells. This work provides a scientific basis for a more comprehensive risk assessment of the environmental behaviors and effects caused by chiral pesticides, as well as for the screening of highly efficient and less biotoxic enantiomeric monomers.

Content-Seam-Preserving Multi-Alignment Network for Visual-Sensor-Based Image Stitching.

As an important representation of scenes in virtual reality and augmented reality, image stitching aims to generate a panoramic image with a natural field-of-view by stitching multiple images together, which are captured by different visual sensors. Existing deep-learning-based methods for image stitching only conduct a single deep homography to perform image alignment, which may produce inevitable alignment distortions. To address this issue, we propose a content-seam-preserving multi-alignment network (CSPM-Net) for visual-sensor-based image stitching, which could preserve the image content consistency and avoid seam distortions simultaneously. Firstly, a content-preserving deep homography estimation was designed to pre-align the input image pairs and reduce the content inconsistency. Secondly, an edge-assisted mesh warping was conducted to further align the image pairs, where the edge information is introduced to eliminate seam artifacts. Finally, in order to predict the final stitched image accurately, a content consistency loss was designed to preserve the geometric structure of overlapping regions between image pairs, and a seam smoothness loss is proposed to eliminate the edge distortions of image boundaries. Experimental results demonstrated that the proposed image-stitching method can provide favorable stitching results for visual-sensor-based images and outperform other state-of-the-art methods.

Feasibility Study on the Classification of Persimmon Trees' Components Based on Hyperspectral LiDAR.

Intelligent management of trees is essential for precise production management in orchards. Extracting components' information from individual fruit trees is critical for analyzing and understanding their general growth. This study proposes a method to classify persimmon tree components based on hyperspectral LiDAR data. We extracted nine spectral feature parameters from the colorful point cloud data and performed preliminary classification using random forest, support vector machine, and backpropagation neural network methods. However, the misclassification of edge points with spectral information reduced the accuracy of the classification. To address this, we introduced a reprogramming strategy by fusing spatial constraints with spectral information, which increased the overall classification accuracy by 6.55%. We completed a 3D reconstruction of classification results in spatial coordinates. The proposed method is sensitive to edge points and shows excellent performance for classifying persimmon tree components.

Associations between workplace violence and suicidal ideation among Chinese medical staff: a propensity score matching analysis.

Physical and mental health problems had been identified as the negative outcomes of workplace violence (WPV) against medical staff. Considering the proven associations between physical and mental health and suicidal ideation, it is reasonable to assume that WPV may associate with suicidal ideation. However, few studies were conducted to explore the relationship between WPV and their suicidal ideation against medical staff. Based on a cross-sectional design, 3, 426 medical staff working in general hospitals were interviewed in Shandong Province, China. Socio-demographic characteristics, work-related factors, psychological variables, WPV, and suicidal ideation were evaluated. Propensity score matching (PSM) was performed to explore the association between WPV and suicidal ideation. The prevalence of suicidal ideation among medical staff was 9.1% (312/3426), and 52.2% (1788/3426) of medical staff reported the WPV experience. Before PSM, we found that the association between WPV and suicidal ideation was statistically significant (aOR = 1.606, p < 0.01). After PSM, there was a statistically significant correlation between WPV and suicidal ideation (aOR = 1.525, p < 0.01). This study supported the correlations between WPV against medical staff and their suicidal ideation. The results of PSM further implied that WPV might cause suicidal ideation among medical staff. Psychological health, especially for suicidal ideation, should be paid attention for medical staff with WPV experiences.

68Ga Fibroblast Activation Protein Inhibitor PET/CT in the Detection of Metastatic Thyroid Cancer: Comparison with 18F-FDG PET/CT.

Background Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) has been proposed as a potential radiotracer for visualizing cancerous lesions, but its utility for identifying metastatic differentiated thyroid cancer (DTC) is not well established in the literature. Purpose To evaluate the clinical utility of 68Ga-FAPI PET/CT for detecting metastatic DTC and to compare the results with those of fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. Materials and Methods Participants with clinically suspected or confirmed metastatic DTC were prospectively enrolled and underwent paired 68Ga-FAPI and 18F-FDG PET/CT from May to August 2020. Histopathologic results and clinical follow-up (mean, 12 months ± 0.7 [SD]; range, 11-13 months) were used as reference standards for the final diagnosis. 18F-FDG and 68Ga-FAPI uptake was compared by using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic accuracy of the two techniques, and the influence of various clinicopathologic characteristics on 18F-FDG and 68Ga-FAPI uptake was evaluated with Mann-Whitney and Kruskal-Wallis tests. Results In total, 35 participants (median age, 44 years; IQR, 28-58 years; 18 [51%] men) were evaluated. In all 35 participants, the 68Ga-FAPI-derived maximum standardized uptake value (SUVmax) was higher than the 18F-FDG-derived SUVmax in the metastatic lateral compartment (6.0 vs 3.5; P = .001), axillary (8.5 vs 4.3; P = .01), mediastinal lymph nodes (9.1 vs 5.0; P = .001), and pulmonary metastases (1.7 vs 1.1; P = .004). 68Ga-FAPI PET/CT had a higher sensitivity than 18F-FDG PET/CT for depicting neck lesions (83% [65 of 78; 95% CI: 73, 90] vs 65% [51 of 78; 95% CI: 54, 75], P = .01) and distant metastases (79% [87 of 110; 95% CI: 71, 86] vs 59% [65 of 110; 95% CI: 50, 68], P < .001). Conclusion Gallium 68-labeled fibroblast activation protein inhibitor PET/CT was superior to fluorine 18 fluorodeoxyglucose PET/CT for depicting metastatic differentiated thyroid cancer, especially in lymph nodes and pulmonary metastases. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Somatostatin receptor imaging with [68Ga]Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma.

PURPOSE: To explore the feasibility of [68Ga]Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with non-keratinizing nasopharyngeal carcinoma (NPC) and to evaluate whether [68Ga]Ga-DOTATATE PET/CT could be used for non-invasive determination of somatostatin receptor 2 (SSTR2) expression in NPC. METHODS: This prospective study included patients with NPC who underwent [68Ga]Ga-DOTATATE PET/CT between February and May 2021. The [68Ga]Ga-DOTATATE and [18F]FDG uptakes in primary and metastatic NPC lesions were calculated and compared, and the [68Ga]Ga-DOTATATE uptake between SSTR2 score groups was analysed. RESULTS: A total of 36 participants (25 patients, initial staging; 11 patients, recurrence detection) were included; 33 patients also underwent [18F]FDG PET/CT for staging/restaging as a part of their routine diagnostic workup. [68Ga]Ga-DOTATATE PET/CT showed an intense tracer uptake in primary and metastatic NPC lesions. The radiotracer uptake was higher with [68Ga]Ga-DOTATATE than with [18F]FDG PET in primary NPC lesions (SUVmax: 12.03 vs. 10.07, P = 0.048; tumour-to-brain ratio: 36.16 vs. 0.86, P < 0.001) and regional lymph node metastases (median SUVmax: 9.11 vs. 6.12, P < 0.001) and comparable in bone and visceral metastases. Importantly, most NPC lesions showed intense SSTR2 expression (85.7%), which was strongly correlated with the [68Ga]Ga-DOTATATE uptake. The SUVmax of SSTR2-negative lesions was significantly lower than that of SSTR2-positive lesions (SUVmax: 4.95 vs. 12.61, P = 0.013). CONCLUSION: [68Ga]Ga-DOTATATE PET/CT is a promising imaging modality for detecting primary and metastatic NPC, with favourable image contrast and comparable diagnostic efficacy when compared to [18F]FDG PET/CT. An intense SSTR2 expression was observed in most NPCs, and this expression was significantly correlated with the [68Ga]Ga-DOTATATE uptake.

Positron emission tomography and computed tomography with [68Ga]Ga-fibroblast activation protein inhibitors improves tumor detection and staging in patients with pancreatic cancer.

PURPOSE: This study aimed to investigate the diagnostic performance of [68Ga]Ga-FAPI PET/CT for primary and metastatic pancreatic carcinoma lesions and compare the results with those of [18F]-fluorodeoxyglucose ([18F]FDG) PET/CT. METHODS: Patients with suspected or diagnosed pancreatic malignancy, who underwent contemporaneous [18F]FDG and [68Ga]Ga-FAPI PET/CT between June 2020 and January 2021, were retrospectively analyzed. Routine contrast-enhanced CT (CE-CT) is performed in all patients as standardized care. Findings were confirmed by histopathology or radiographic follow-up. We compared radiotracer uptake, diagnostic performance, and TNM (tumor-node-metastasis) classifications. RESULTS: We evaluated 36 participants (25/36 men; median age, 60 years), including 26 patients with pancreatic malignancies and ten patients with pancreatic benign lesions. [68Ga]Ga-FAPI PET/CT showed higher radiotracer uptake and higher sensitivity than [18F]FDG PET/CT in evaluating primary tumors (SUVmax, 21.4 vs. 4.8; sensitivity, 100% vs. 73.1%), involved lymph nodes (SUVmax, 8.6 vs. 2.7; sensitivity, 81.8% vs. 59.1%), and metastases (SUVmax, 7.9 vs. 3.5; sensitivity, 91.5% vs. 44.0%); Compared with [18F]FDG, [68Ga]Ga-FAPI PET/CT upstaged six patients' TNM staging (6/23, 26.1%) and changed two patients' clinical management (2/23, 8.7%). Compared with CE-CT, [68Ga]Ga-FAPI PET/CT upgraded TNM staging in five patients (5/23, 21.7%) and changed the therapeutic regimen in only one patient (1/23, 4.3%). Intense [68Ga]Ga-FAPI uptake was observed throughout the pancreas in 12/26 pancreatic malignancies; dual-time point [68Ga]Ga-FAPI PET/CT may differentiate pancreatitis from malignancy. CONCLUSIONS: Compared with [18F]FDG PET/CT, [68Ga]Ga-FAPI PET/CT shows higher sensitivity in detecting primary pancreatic tumors, involved lymph nodes, and metastases and is superior in terms of TNM staging. Prospective trials with larger patient population are needed to evaluate whether [68Ga]Ga-FAPI PET/CT could elicit treatment modification in pancreatic cancer when compared with standard of care imaging.