Human population history at the crossroads of East and Southeast Asia since 11,000 years ago.

Past human genetic diversity and migration between southern China and Southeast Asia have not been well characterized, in part due to poor preservation of ancient DNA in hot and humid regions. We sequenced 31 ancient genomes from southern China (Guangxi and Fujian), including two ∼12,000- to 10,000-year-old individuals representing the oldest humans sequenced from southern China. We discovered a deeply diverged East Asian ancestry in the Guangxi region that persisted until at least 6,000 years ago. We found that ∼9,000- to 6,000-year-old Guangxi populations were a mixture of local ancestry, southern ancestry previously sampled in Fujian, and deep Asian ancestry related to Southeast Asian Hòabìnhian hunter-gatherers, showing broad admixture in the region predating the appearance of farming. Historical Guangxi populations dating to ∼1,500 to 500 years ago are closely related to Tai-Kadai and Hmong-Mien speakers. Our results show heavy interactions among three distinct ancestries at the crossroads of East and Southeast Asia.

Middle and Late Pleistocene Denisovan subsistence at Baishiya Karst Cave.

Genetic and fragmented palaeoanthropological data suggest that Denisovans were once widely distributed across eastern Eurasia1-3. Despite limited archaeological evidence, this indicates that Denisovans were capable of adapting to a highly diverse range of environments. Here we integrate zooarchaeological and proteomic analyses of the late Middle to Late Pleistocene faunal assemblage from Baishiya Karst Cave on the Tibetan Plateau, where a Denisovan mandible and Denisovan sedimentary mitochondrial DNA were found3,4. Using zooarchaeology by mass spectrometry, we identify a new hominin rib specimen that dates to approximately 48-32 thousand years ago (layer 3). Shotgun proteomic analysis taxonomically assigns this specimen to the Denisovan lineage, extending their presence at Baishiya Karst Cave well into the Late Pleistocene. Throughout the stratigraphic sequence, the faunal assemblage is dominated by Caprinae, together with megaherbivores, carnivores, small mammals and birds. The high proportion of anthropogenic modifications on the bone surfaces suggests that Denisovans were the primary agent of faunal accumulation. The chaîne opératoire of carcass processing indicates that animal taxa were exploited for their meat, marrow and hides, while bone was also used as raw material for the production of tools. Our results shed light on the behaviour of Denisovans and their adaptations to the diverse and fluctuating environments of the late Middle and Late Pleistocene of eastern Eurasia.

ETHYLENE RESPONSE FACTOR 070 inhibits flowering in Pak-choi by indirectly impairing BcLEAFY expression.

APETALA2/ethylene responsive factors respond to ethylene and participate in many biological and physiological processes, such as plant morphogenesis, stress resistance, and hormone signal transduction. Ethylene responsive factor 070 (BcERF070) is important in flowering. However, the underlying molecular mechanisms of BcERF070 in floral transition in response to ethylene signaling have not been fully characterized. Herein, we explored the function of BcERF070 in Pak-choi [Brassica campestris (syn. Brassica rapa) ssp. chinensis]. Ethylene treatment induced BcERF070 expression and delayed flowering in Pak-choi. Silencing of BcERF070 induced flowering in Pak-choi. BcERF070 interacted with major latex protein-like 328 (BcMLP328), which forms a complex with helix-loop-helix protein 30 (BcbHLH30) to enhance the transcriptional activity of BcbHLH30 on LEAFY (BcLFY), ultimately promoting flowering. However, BcERF070 impaired the BcMLP328-BcbHLH30 complex activation of LEAFY (BcLFY), ultimately inhibiting flowering in Pak-choi. BcERF070 directly promoted the expression of the flowering inhibitor gene B-box 29 (BcBBX29) and delayed flowering by reducing FLOWERING LOCUS T (BcFT) expression. These results suggest that BcERF070 mediates ethylene-reduced flowering by impairing the BcMLP328-BcbHLH30 complex activation of BcLFY and by directly promoting the gene expression of the flowering inhibition factor BcBBX29 to repress BcFT expression. The findings contribute to understanding the molecular mechanisms underlying floral transition in response to ethylene in plants.

Exploration of Novel Meso-C═N-BODIPY-Based AIE Fluorescent Rotors with Large Stokes Shifts for Organelle-Viscosity Imaging.

The research on fluorescent rotors for viscosity has attracted extensive interest to better comprehend the close relationships of microviscosity variations with related diseases. Although scientists have made great efforts, fluorescent probes for cellular viscosity with both aggregation-induced emissions (AIEs) and large Stokes shifts to improve sensing properties have rarely been reported. Herein, we first report four new meso-C═N-substituted BODIPY-based rotors with large Stokes shifts, investigate their viscosity/AIE characteristics, and perform cellular imaging of the viscosity in subcellular organelles. Interestingly, the meso-C═N-phenyl group-substituted probe 6 showed an obvious 594 nm fluorescence enhancement in glycerol and a moderate 650 nm red AIE emission in water. Further, on attaching CF3 to the phenyl group, a similar phenomenon was observed for 7 with red-shifted emissions, attributed to the introduction of a phenyl group, which plays a key role in the red AIE emissions and large Stokes shifts. Comparatively, for phenyl-group-free probes, both the meso-C═N-trifluoroethyl group and thiazole-substituted probes (8 and 9) exhibited good viscosity-responsive properties, while no AIE was observed due to the absence of phenyl groups. For cellular experiments, 6 and 9 showed good lysosomal and mitochondrial targeting properties, respectively, and were further successfully used for imaging viscosity through the preincubation of monensin and lipopolysaccharide (LPS), indicating that C═N polar groups potentially work as rotatable moieties and organelle-targeting groups, and the targeting difference might be ascribed to increased charges of thiazole. Therefore, in this study, we investigated the structural relationships of four meso-C═N BODIPY-based rotors with respect to their viscosity/AIE characteristics, subcellular-targeting ability, and cellular imaging for viscosity, potentially serving as AIE fluorescent probes with large Stokes shifts for subcellular viscosity imaging.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Optimization of the synthesis of BET BD2 selective inhibitor XY153.

XY153 is a promising BET BD2 inhibitor with an IC50 value of 0.79 nM against BRD4 BD2. It shows 354-fold selectivity over BRD4-BD1 and 6-fold selectivity over other BET BD2 domains. However, the reported synthesis route of XY153 and its derivatives are extremely poor-yielding. After the synthesis of three key fragments, XY153 can only be obtained with a yield of 1.3 % in the original four-step reaction. In this study, we reported a three-step alternative route in the synthesis process of XY153. The reaction conditions for this route were thoroughly investigated and optimized, resulting in a significantly improved yield of 61.5 %. This efficient synthesis route establishes a robust chemical foundation for the rapid synthesis of XY153 derivatives as BET BD2 inhibitors in the near future.

Risk stratification for 1- to 2-cm gastric gastrointestinal stromal tumors: visual assessment of CT and EUS high-risk features versus CT radiomics analysis.

OBJECTIVES: To investigate the ability of CT and endoscopic sonography (EUS) in predicting the malignant risk of 1-2-cm gastric gastrointestinal stromal tumors (gGISTs) and to clarify whether radiomics could be applied for risk stratification. METHODS: A total of 151 pathologically confirmed 1-2-cm gGISTs from seven institutions were identified by contrast-enhanced CT scans between January 2010 and March 2021. A detailed description of EUS morphological features was available for 73 gGISTs. The association between EUS or CT high-risk features and pathological malignant potential was evaluated. gGISTs were randomly divided into three groups to build the radiomics model, including 74 in the training cohort, 37 in validation cohort, and 40 in testing cohort. The ROIs covering the whole tumor volume were delineated on the CT images of the portal venous phase. The Pearson test and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature selection, and the ROC curves were used to evaluate the model performance. RESULTS: The presence of EUS- and CT-based morphological high-risk features, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not differ between very-low and intermediate risk 1-2-cm gGISTs (p > 0.05). The radiomics model consisting of five radiomics features showed favorable performance in discrimination of malignant 1-2-cm gGISTs, with the AUC of the training, validation, and testing cohort as 0.866, 0.812, and 0.766, respectively. CONCLUSIONS: Instead of CT- and EUS-based morphological high-risk features, the CT radiomics model could potentially be applied for preoperative risk stratification of 1-2-cm gGISTs. KEY POINTS: • The presence of EUS- and CT-based morphological high-risk factors, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not correlate with the pathological malignant potential of 1-2-cm gGISTs. • The CT radiomics model could potentially be applied for preoperative risk stratification of 1-2-cm gGISTs.

Exploring causal mechanisms and essential factors in the prevention and control of chlamydia in Guangdong, Southern China: a study protocol.

BACKGROUND: Chlamydia Trachomatis (CT) is among the most prevalent sexually transmitted diseases (STDs) globally. According to the World Health Organization, more than 131 million people get infected with CT annually. CT is usually transmitted via sexual contact or perinatal exposure and can result in severe long-term complications. In developing nations, particularly, the prevention and control of CT is challenging. Hence, this study will explore the feedback mechanisms of chlamydia prevention and control, as well as identify the essential factors affecting the control and prevention of this infection in China. METHODS: Our study will employ a mixed-methods research design that encompasses both qualitative and quantitative methods. Firstly, we will develop a causal loop diagram (CLD) based on the literature review and optimize it via in-depth interviews with stakeholders. Additionally, we will utilize a quantitative method called MICMAC(Impact Matrix Cross-Reference Multiplication Applied to a Classification tool) to obtain consensus among different stakeholders and pinpoint the key information. Next, the CLD will be transformed into a system dynamics model (SDM) to evaluate the feedback mechanisms within the CLD. The causality in the CLD will be modeled using mathematical equations, which facilitate the transformation into an SDM. As such, we will be able to analyze the dynamic behavior of the system and its response to different decisions. DISCUSSION: Our study offers a systematic perspective on the control and prevention of chlamydia infection through system dynamics modeling, examining the dynamic properties and background factors of the system. The creation of the CLD affords stakeholders the chance to comprehend the functionality of their relationships and improve cooperation. Consequently, by evaluating the outcomes of these simulations, it will be possible to analyze and determine potential interventions and their effects on chlamydia infections. This modeling approach can help us gain insight into the dynamic characteristics of the system, evaluate the potential outcomes of different decisions, and design control strategies to either stabilize the system or adjust its behavior.

Improving eye care quality through brief verbal intervention on optometry service provider by using unannounced standardized patient with refractive error: study protocol for a randomized controlled trial.

BACKGROUND: Improper refractive correction can be harmful to eye health, aggravating the burden of vision impairment. During most optometry clinical consultations, practitioner-patient interactions play a key role. Maybe it is feasible for patients themselves to do something to get high-quality optometry. But the present empirical research on the quality improvement of eye care needs to be strengthened. The study aims to test the effect of the brief verbal intervention (BVI) through patients on the quality of optometry service. METHODS: This study will take unannounced standardized patient (USP) with refractive error as the core research tool, both in measurement and intervention. The USP case and the checklist will be developed through a standard protocol and assessed for validity and reliability before its full use. USP will be trained to provide standardized responses during optical visits and receive baseline refraction by the skilled study optometrist who will be recruited within each site. A multi-arm parallel-group randomized trial will be used, with one common control and three intervention groups. The study will be performed in four cities, Guangzhou and three cities in Inner Mongolia, China. A total of 480 optometry service providers (OSPs) will be stratified and randomly selected and divided into four groups. The common control group will receive USP usual visits (without intervention), and three intervention groups will separately receive USP visits with three kinds of BVI on the patient side. A detailed outcome evaluation will include the optometry accuracy, optometry process, patient satisfaction, cost information and service time. Descriptive analysis will be performed for the survey results, and the difference in outcomes between interventions and control providers will be compared and statistically tested using generalized linear models (GLMs). DISCUSSION: This research will help policymakers understand the current situation and influencing factors of refractive error care quality, and then implement precise policies; at the same time, explore short and easy interventions for patients to improve the quality of optometry service. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200062819. Registered on August 19, 2022.

Diagnostic performance of gadoxetic acid-enhanced abbreviated magnetic resonance imaging protocol in small hepatocellular carcinoma (≤2 cm) in high-risk patients.

BACKGROUND: Biannual Ultrasound showed insufficient sensitivity in detecting small or early-stage hepatocellular carcinoma (HCC). Abbreviated magnetic resonance imaging (A-MRI) protocols with fewer sequences demonstrated higher HCC detection sensitivity than ultrasound with acceptable cost and examination time. PURPOSE: To compare the diagnostic performance of gadoxetic acid-enhanced A-MRI with a full sequence MRI (F-MRI) protocol for small HCC (≤2 cm) in cirrhotic or hepatitis B virus-infected high-risk patients. MATERIAL AND METHODS: Two hundred and four consecutive patients with 166 pathologically confirmed small HCC who underwent preoperative gadoxetic acid-enhanced MRI were retrospectively included. A-MRI set comprised T1-weighted hepatobiliary phase imaging, T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient mapping. Two independent radiologists blinded to clinical data assessed the A-MRI set and F-MRI set. Per-patient HCC and per-lesion HCC diagnostic performance were compared. RESULTS: Per-patient HCC detection sensitivity of A-MRI set was 93.8% and 91.2% for observer 1 and observer 2, and, for the F-MRI set, the per-patient HCC detection sensitivity was 96.6% and 95.2%, respectively. There was no significant difference in per-patient sensitivity, specificity and per-lesion HCC detection sensitivity between the two imaging sets for both readers. (P = 0.06-0.25) The A-MRI set showed higher sensitivity on HCC without arterial phase hyperenhancement, and the F-MRI set demonstrated with higher sensitivity on HCC with arterial phase hyperenhancement (P < 0.05). CONCLUSION: A-MRI using diagnostic criteria including hypointensity on hepatobiliary phase plus mild to moderate hyperintensity on T2-weighted imaging or restricted diffusion demonstrated comparable sensitivity and specificity for small HCC compared to the F-MRI protocol in high-risk patients.

BcMYB111 Responds to BcCBF2 and Induces Flavonol Biosynthesis to Enhance Tolerance under Cold Stress in Non-Heading Chinese Cabbage.

Flavonols have been shown to respond to a variety of abiotic stresses in plants, including cold stress. Higher total flavonoid content was found in non-heading Chinese cabbage (NHCC, Brassica campestris (syn. Brassica rapa) ssp. chinensis) after cold stress. A non-targeted metabolome analysis showed a significant increase in flavonol content, including that of quercetin and kaempferol. Here, we found that an R2R3-MYB transcription factor, BcMYB111, may play a role in this process. BcMYB111 was up-regulated in response to cold treatment, with an accompanying accumulation of flavonols. Then, it was found that BcMYB111 could regulate the synthesis of flavonols by directly binding to the promoters of BcF3H and BcFLS1. In the transgenic hairy roots of NHCC or stable transgenic Arabidopsis, overexpression of BcMYB111 increased flavonol synthesis and accumulation, while these were reduced in virus-induced gene silencing lines in NHCC. After cold stress, the higher proline content and lower malondialdehyde (MDA) content showed that there was less damage in transgenic Arabidopsis than in the wild-type (WT). The BcMYB111 transgenic lines performed better in terms of antioxidant capacity because of their lower H2O2 content and higher superoxide dismutase (SOD) and peroxidase (POD) enzyme activities. In addition, a key cold signaling gene, BcCBF2, could specifically bind to the DRE element and activate the expression of BcMYB111 in vitro and in vivo. The results suggested that BcMYB111 played a positive role in enhancing the flavonol synthesis and cold tolerance of NHCC. Taken together, these findings reveal that cold stress induces the accumulation of flavonols to increase tolerance via the pathway of BcCBF2-BcMYB111-BcF3H/BcFLS1 in NHCC.

Microvascular invasion of small hepatocellular carcinoma can be preoperatively predicted by the 3D quantification of MRI.

OBJECTIVES: To explore the importance of three-dimensional (3D) quantitative analysis during gadoxetic acid-enhanced magnetic resonance imaging (MRI) of microvascular invasion (MVI) and early recurrence (< 2 years) after surgery of single hepatocellular carcinoma (HCC) ≤ 3 cm. METHODS: Two hundred fourteen patients with pathologically confirmed HCC (training cohort: n = 169; validation cohort: n = 45) were included retrospectively. The 3D quantitative parameters (volume, sphericity, and compacity) and conventional MRI features were analyzed. The significant predictors for MVI were identified using univariate and multivariate logistic regression analyses. Nomograms were constructed from the prediction model, and the relationship between the significant predictors and early recurrence rates was evaluated using the Kaplan-Meier method. RESULTS: Tumor sphericity (odds ratio [OR] = 0.000; p < 0.001), non-smooth tumor margin (OR = 3.353; p = 0.015), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 14.067; p = 0.003) were independent significant factors for MVI. When these three factors were combined, the diagnostic specificity of the training and validation cohorts was 97.0 (128/132) and 87.9 (29/33), respectively. The nomogram based on the predictive model performed satisfactorily in the training (C-index: 0.885) and validation (C-index: 0.869) cohorts. Early recurrence rates of patients with two or three significant factors were significantly higher than those with none in the training (29.1% vs. 10.2%, p = 0.007) and validation (36.4% vs. 6.7%, p = 0.037) cohorts. CONCLUSIONS: Lower sphericity combined with non-smooth tumor margin and peritumoral hypointensity on HBP are potential predictive factors for MVI and associated with early recurrence after surgery of HCC ≤ 3 cm. KEY POINTS: • Lower sphericity, non-smooth tumor margin, and peritumoral hypointensity on HBP were important indicators of the occurrence of MVI in HCC. • The combinational model prepared from these findings satisfactorily predicted MVI, and the presence of these predictors was associated with an early recurrence rate after surgical resection in HCC patients. • This model could help clinicians in the preoperative management of small HCC ≤ 3 cm.

Investigate the metabolic profile and potential active compounds of Fructus Corni in the treatment of heart failure by applying ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry and network pharmacology.

Fructus Corni has been reported to contain a wide variety of pharmacological effects and previous studies had revealed that Fructus Corni might protect the cardiac indices. However, the all-encompassing metabolic profile of Fructus Corni has not been well illuminated. In this research, high-sensitivity ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry method was adopted to identify the metabolic profile after oral administration of Fructus Corni extract, especially the metabolic characterization of serum and heart, for which the targets and signaling pathways about heart failure were hunted through compound-target-disease-pathway intersection network. Ultimately, 37 ingredients were identified in Fructus Corni extract, and 22 prototypes and 134 metabolites that were identified in serum, heart, feces, and urine were tentatively characterized, which contained iridoids, flavonoids, tannins, organic acids, and others. Additionally, 10 putative key compounds including four prototypes and six phase I metabolites were screened by network pharmacology and molecular docking, among which, secoxyloganin (P7), loganin (P14), cornuside III (P17) and cornuside (P20) were the absorbed compounds to represent the potential active ingredients of Fructus Corni engaged in heart failure condition. In general, this method provided the combined strategy to preliminarily settle the complex of Fructus Corni's metabolic profiling and anti-heart failure pharmacologic activities.

Identifying a Three-Gene Signature and Associated Drugs for Hepatitis B Virus-Related Hepatocellular Carcinoma Using Comprehensive Bioinformatics Analysis.

Liver cancer is one of the most common cancer forms and a significant contributor to global cancer-associated mortality. Hepatitis B virus (HBV) infection contributes enormously to HCC development and progression. Despite this, the molecular basis of liver tumorigenesis is not clear. This work focused on identifying the relevant genetic markers and available drugs for treating HBV-related HCC. Differentially expressed genes (DEGs) from HBV-related HCC samples and corresponding healthy samples were identified from GSE62232 and GSE121248 datasets from the GEO2R repository (Gene Expression Omnibus). The Venn diagram software screened the overlapping DEGs between these two datasets. The DEGs were functionally assessed using protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses by different bioinformatic methods, and hub genes were screened. Hub genes and related drugs were verified by the GEPIA2 (Gene Expression Profiling Interactive Analysis) web server and the Quartata Web online platform. Overall, 116 DEGs (88 up-regulated and 28 down-regulated) related to signal transduction and metabolic pathways were identified. The nine significant target hub genes were TOP2A, RRM2, DTL, ECT2, ASPM, ANLN, BUB1B, CCNB1, and CDK1. Moreover, one screened drug, Fostamatinib, was targeted to CDK1. Our study identified three genes and associated drugs as probable targets for studying HBV-related HCC.

Predictive Modeling of Morbidity and Mortality in Patients Hospitalized With COVID-19 and its Clinical Implications: Algorithm Development and Interpretation.

BACKGROUND: The COVID-19 pandemic began in early 2021 and placed significant strains on health care systems worldwide. There remains a compelling need to analyze factors that are predictive for patients at elevated risk of morbidity and mortality. OBJECTIVE: The goal of this retrospective study of patients who tested positive with COVID-19 and were treated at NYU (New York University) Langone Health was to identify clinical markers predictive of disease severity in order to assist in clinical decision triage and to provide additional biological insights into disease progression. METHODS: The clinical activity of 3740 patients at NYU Langone Hospital was obtained between January and August 2020; patient data were deidentified. Models were trained on clinical data during different parts of their hospital stay to predict three clinical outcomes: deceased, ventilated, or admitted to the intensive care unit (ICU). RESULTS: The XGBoost (eXtreme Gradient Boosting) model that was trained on clinical data from the final 24 hours excelled at predicting mortality (area under the curve [AUC]=0.92; specificity=86%; and sensitivity=85%). Respiration rate was the most important feature, followed by SpO2 (peripheral oxygen saturation) and being aged 75 years and over. Performance of this model to predict the deceased outcome extended 5 days prior, with AUC=0.81, specificity=70%, and sensitivity=75%. When only using clinical data from the first 24 hours, AUCs of 0.79, 0.80, and 0.77 were obtained for deceased, ventilated, or ICU-admitted outcomes, respectively. Although respiration rate and SpO2 levels offered the highest feature importance, other canonical markers, including diabetic history, age, and temperature, offered minimal gain. When lab values were incorporated, prediction of mortality benefited the most from blood urea nitrogen and lactate dehydrogenase (LDH). Features that were predictive of morbidity included LDH, calcium, glucose, and C-reactive protein. CONCLUSIONS: Together, this work summarizes efforts to systematically examine the importance of a wide range of features across different endpoint outcomes and at different hospitalization time points.

Feasibility of One-Day PET/CT Scanning Protocol with 68Ga-DOTA-FAPI-04 and 18F-FDG for the Detection of Ovarian Cancer Recurrence and Metastasis.

Objective: The objective of this study was to investigate the feasibility of 1-d 68Ga-DOTA-FAPI-04 and 18F-FDG (2-deoxy-2[18F]fluoro-d-glucose) positron emission tomography/computed tomography (PET/CT) for detecting ovarian cancer recurrence and metastasis. Materials and Methods: Fifty-two patients who underwent 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT were divided into 1- and 2-d groups. Image acquisition, injection time, and total waiting time were compared. For the 68Ga-DOTA-FAPI-04 PET/CT scans, low-dose CT scans and low injection dosages were employed, and total radiation dose was assessed for both protocols. The comparative analysis included assessment of patient-based detection rates and lesion-based diagnostic efficacy. Results: The total waiting time was significantly shorter in the 1-d group than in the 2-d group (p = 0.000). The radiation doses stemming from internal radiation and external radiation between the groups showed no differences (p = 0.151 vs. 0.716). In the patient-based analysis, the detection rates for local recurrence, peritoneal, lymph node, and other metastases were not significantly different in both protocols (p ∈ [0.351, 1.000]). For the lesion-based analysis, no differences were noted in terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (p ∈ [0.371, 1.000]). Conclusions: The 1-d PET/CT protocol reduced waiting time and exhibited equivalent detectability compared with the 2-d protocol, suggesting its clinical value.

Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma with extranodal involvement.

PURPOSE: The objective of this investigation is to explore the capability of baseline 18F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI). METHODS: 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index). RESULTS: 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan--Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05). CONCLUSIONS: The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI.

Comparison of 68 Ga-FAPI-04 PET/CT with 18 F-FDG PET/CT for diagnosis and staging of gastric and colorectal cancer.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of 68 Ga-FAPI-04 PET/computed tomography (CT) for the diagnosis of primary and metastatic gastric cancer and colorectal cancer lesions as compared with 18 F-FDG PET/CT. MATERIALS AND METHODS: Fifty-nine patients who underwent both 18 F-FDG and 68 Ga-FAPI-04 for initial staging or restaging were enrolled. Histopathological findings and clinical imaging follow-up were used as the reference standard. The diagnostic performance and TNM staging of the two tracers were calculated and compared. The maximum standardized uptake value (SUV max ), tumour-to-mediastinal blood pool ratio (TBR) (lesions SUV max /ascending aorta SUV mean ), and tumour-to-normal liver parenchyma ratio (TLR) (lesions SUV max /liver SUV mean ) of primary and metastatic lesions between two imaging modalities were measured and compared using the Wilcoxon signed-rank test and paired t -test. RESULTS: The two imaging agents are comparable for the detection of primary tumors. The sensitivity of 68 Ga-FAPI-04 PET/CT was higher than that of 18 F-FDG PET/CT for detecting lymph node metastases, peritoneal metastases, liver metastases, and bone metastases. In the patient-based analysis, the TLR for all lesions was significantly higher with 68 Ga-FAPI-04 PET/CT than with 18 F-FDG PET/CT (all P  < 0.05). The accuracy (92.2 vs. 70.3%, P  = 0.002) and sensitivity of 68 Ga-FAPI-04 were significantly higher than that of 18 F-FDG (78.6 vs. 71.4%, P  = 0.011) in determining the lymph node status. 68 Ga-FAPI-04 has a higher accuracy in staging ( P  = 0.041), which is mainly due to the ability of distant metastases detection. CONCLUSION: 68 Ga-FAPI-04 PET/CT may be superior in evaluating the diagnostic efficiency and staging accuracy of gastric and colorectal cancer.

Human Biodistribution and Radiation Dosimetry of the Targeting Fibroblast Growth Factor Receptor 1-Positive Tumors Tracer [68Ga]Ga-DOTA-FGFR1-Peptide.

Objective: [68Ga]Ga-DOTA-FGFR1-peptide is a novel positron emission tomography (PET) radiotracer targeting fibroblast growth factor receptor 1 (FGFR1). This study aimed to evaluate the safety, biodistribution, radiation dosimetry, and imaging potential of [68Ga]Ga-DOTA-FGFR1-peptide. Methods: The FGFR1-targeting peptide DOTA-(PEG2)-KAEWKSLGEEAWHSK was synthesized by manual solid-phase peptide synthesis and high-performance liquid chromatography purification, and labeled with 68Ga with DOTA as chelating agent. We recruited 14 participants and calculated the radiation dose of 4 of these pathologically confirmed nontumor subjects using OLINDA/EXM 2.2.0 software. At the same time, the imaging potential in 10 of these lung cancer patients was evaluated. Results: The biodistribution of [68Ga]Ga-DOTA-FGFR1-peptide in 4 subjects showed the highest uptake in the bladder and kidney. Dosimetry analysis indicated that the bladder wall received the highest effective dose (3.73E-02 mSv/MBq), followed by the lungs (2.36E-03 mSv/MBq) and red bone marrow (2.09E-03 mSv/MBq). No normal organs were found to have excess specific absorbed doses. The average systemic effective dose was 4.97E-02 mSv/MBq. The primary and metastatic tumor lesions were clearly visible on PET/computed tomography (CT) images in 10 patients. Conclusion: Our results indicate that [68Ga]Ga-DOTA-FGFR1-peptide has a good dosimetry profile and can be used safely in humans, and it has significant potential value for clinical PET/CT imaging.

Therapeutic potential of ADSC-EV-derived lncRNA DLEU2: A novel molecular pathway in alleviating sepsis-induced lung injury via the miR-106a-5p/LXN axis.

This study investigates the molecular mechanisms by which extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSCs) promote M2 polarization of macrophages and thus reduce lung injury caused by sepsis. High-throughput sequencing was used to identify differentially expressed genes related to long non-coding RNA (lncRNA) in ADSC-derived EVs (ADSC-EVs) in sepsis lung tissue. Weighted gene co-expression network analysis (WGCNA) was employed to predict the downstream target genes of the lncRNA DLEU2. The RNAInter database predicted miRNAs that interact with DLEU2 and LXN. Functional and pathway enrichment analyses were performed using GO and KEGG analysis. A mouse model of sepsis was established, and treatment with a placebo or ADSC-EVs was administered, followed by RT-qPCR analysis. ADSC-EVs were isolated and identified. In vitro cell experiments were conducted using the mouse lung epithelial cell line MLE-12, mouse macrophage cell line RAW264.7, and mouse lung epithelial cell line (LEPC). ADSC-EVs were co-cultured with RAW264.7 and MLE-12/LEPC cells to study the regulatory mechanism of the lncRNA DLEU2. Cell viability, proliferation, and apoptosis of lung injury cells were assessed using CCK-8, EdU, and flow cytometry. ELISA was used to measure the levels of inflammatory cytokines in the sepsis mouse model, flow cytometry was performed to determine the number of M1 and M2 macrophages, lung tissue pathology was evaluated by H&E staining, and immunohistochemistry was conducted to examine the expression of proliferation- and apoptosis-related proteins. High-throughput sequencing and bioinformatics analysis revealed enrichment of the lncRNA DLEU2 in ADSC-EVs in sepsis lung tissue. Animal and in vitro cell experiments showed increased expression of the lncRNA DLEU2 in sepsis lung tissue after treatment with ADSC-EVs. Furthermore, ADSC-EVs were found to transfer the lncRNA DLEU2 to macrophages, promoting M2 polarization, reducing inflammation response in lung injury cells, and enhancing their viability, proliferation, and apoptosis inhibition. Further functional experiments indicated that lncRNA DLEU2 promotes M2 polarization of macrophages by regulating miR-106a-5p/LXN, thereby enhancing the viability and proliferation of lung injury cells and inhibiting apoptosis. Overexpression of miR-106a-5p could reverse the biological effects of ADSC-EVs-DLEU2 on MLE-12 and LEPC in vitro cell models. Lastly, in vivo animal experiments confirmed that ADSC-EVs-DLEU2 promotes high expression of LXN by inhibiting the expression of miR-106a-5p, further facilitating M2 macrophage polarization and reducing lung edema, thus alleviating sepsis-induced lung injury. lncRNA DLEU2 in ADSC-EVs may promote M2 polarization of macrophages and enhance the viability and proliferation of lung injury cells while inhibiting inflammation and apoptosis reactions, thus ameliorating sepsis-induced lung injury in a mechanism involving the regulation of the miR-106a-5p/LXN axis.