Biology of Callistethus plagiicollis (Coleoptera: Scarabaeoidea: Rutelinae) and comparative morphology of its larvae.

Larvae of the beetle subfamily Rutelinae are poorly described in the literature. Notably, the morphology of the larvae of Callistethus plagiicollis Fairmaire has not previously been analyzed. Here, we report for the first time that these larvae feed on the tubers and roots of Gastrodia elata Blume, an important traditional Chinese herbal medicine, which causes a reduction in the yield and economic value of G. elata. We employed scanning electron microscopy and light microscopy to investigate the morphology and occurrence regularity of egg, larvae, pupae, and adult specimens of C. plagiicollis collected from the G. elata planting base in Guizhou Province, China, with a focus on the ultrastructure of mature larvae. The results revealed one generation of C. plagiicollis per year in the study area and three instar stages of larvae. Mature larvae were identified by the following characteristics: raster without palidia with a large number of hamate setae, antennal apex containing seven sensilla basiconica, larval haptomerum containing eight sensilla styloconica and four enlarged heli, and seven longitudinally arranged stridulatory teeth on the stipes of the maxilla. The combination of scanning electron and light microscopy effectively revealed the difference between membranous and sclerotized structures, ensuring accurate identification of C. plagiicollis larvae. By determining the feeding characteristics and occurrence regularity of C. plagiicollis, this study has implications for improved pest management in G. elata crops. RESEARCH HIGHLIGHTS: We identified C. plagiicollis as a new pest of G. elata, a traditional Chinese medicine Scanning electron and light microscopy were combined to analyze the morphology of the mature larvae of C. plagiicollis for the first time We determined the feeding characteristics and occurrence regularity of C. plagiicollis, which can be used to develop effective pest management strategies.

Application of a nomogram from coagulation-related biomarkers and C1q and total bile acids in distinguishing advanced and early-stage lung cancer.

BACKGROUND: This study aimed to establish a nomogram to distinguish advanced- and early-stage lung cancer based on coagulation-related biomarkers and liver-related biomarkers. METHODS: A total of 306 patients with lung cancer and 172 patients with benign pulmonary disease were enrolled. Subgroup analyses based on histologic type, clinical stage, and neoplasm metastasis status were carried out and multivariable logistic regression analysis was applied. Furthermore, a nomogram model was developed and validated with bootstrap resampling. RESULTS: The concentrations of complement C1q, fibrinogen, and D-dimers, fibronectin, inorganic phosphate, and prealbumin were significantly changed in lung cancer patients compared to benign pulmonary disease patients. Multiple regression analysis based on subgroup analysis of clinical stage showed that compared with early-stage lung cancer, female (P < 0.001), asymptomatic admission (P = 0.001), and total bile acids (P = 0.011) were negatively related to advanced lung cancer, while C1q (P = 0.038), fibrinogen (P < 0.001), and D-dimers (P = 0.001) were positively related. A nomogram model based on gender, symptom, and the levels of total bile acids, C1q, fibrinogen, and D-dimers was constructed for distinguishing advanced lung cancer and early-stage lung cancer, with an area under the receiver operating characteristic curve of 0.919. The calibration curve for this nomogram revealed good predictive accuracy (P-Hosmer-Lemeshow = 0.697) between the predicted probability and the actual probability. CONCLUSIONS: We developed a nomogram based on gender, symptom, and the levels of fibrinogen, D-dimers, total bile acids, and C1q that can individually distinguish early- and advanced-stage lung cancer.

First report of the complete mitochondrial genome of 3 beetles (Coleoptera: Scarabaeidae) harming Gastrodia elata (Asparagales: Orchidaceae).

Gastrodia elata Blume, a valuable traditional Chinese medicine with significant clinical and nutritional importance, is a fungal heterotrophic orchid. We present the first report of the mitochondrial genome structure and characteristics of 3 Scarabaeidae pests affecting G. elata: Sophrops peronosporus Gu & Zhang, Anomala rufiventris Kollar & Redtenbacher, and Callistethus plagiicollis Fairmaire. Each mitogenome contained 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and a control region, with no gene rearrangements observed. All 21 tRNAs, except trnS1 that lacks a dihydrouridine, had a stable cloverleaf secondary structure. Maximum likelihood and Bayesian inference analyses based on the 13 PCGs produced 2 topologically similar phylogenetic trees, both of with high nodal support. Larvae of these Scarabaeidae pests cause substantial damage by gnawing on the tubers and roots of G. elata, leading to reduced yield and compromised quality. These findings contribute to phylogenetic studies of Scarabaeidae, expand knowledge of G. elata pests, and offer valuable reference materials for their identification and control.

Alteration of serum bile acids in non-small cell lung cancer identified by a validated LC-MS/MS method.

BACKGROUND: Bile acids (BA) are important metabolites and serve as signaling molecules, which are involve in multiple cancer-related signaling pathways. METHODS: A validated LC-MS/MS approach was applied in a case-control study with 220 non-small cell lung cancer (NSCLC) patients and 244 matched healthy controls. The concentrations of seven common types of BAs in serum were determined and compared. Subgroup analyses based on demographic factor, lifestyle, pathologic types and tumor stage were conducted. Machine learning analysis was performed for NSCLC classification. RESULTS: Serum levels of primary BAs, including cholic acid (CA), taurocholic acid (TCA) and glycocholic acid (GCA), were upregulated, while lithocholic acid (LCA), a type of secondary BA, was downregulated in NSCLC patients compared with healthy controls in overall analysis. Higher level of chenodeoxycholic acid (CDCA) and lower level of ursodeoxycholic acid (UDCA) were observed in female, elder, overweight patients, as well as patients without alcohol use in comparison with controls. CDCA and CA levels were higher only in lung adenocarcinoma (LUAD), and UDCA and DCA levels were lower only in squamous cell carcinoma (LUSC), while the concentrations of TCA, GCA, and LCA were altered prevalently in LUAD and LUSC patients. For discrimination of NSCLC from healthy people, the area under the receiver operating characteristics (ROC) curve of the models through support vector machine (SVM) approach was 0.91 (95% CI 0.88-0.94) in the training set and 0.84 (95% CI 0.78-0.91) in the validation set, respectively. CONCLUSIONS: Serum BAs were altered in NSCLC patients compared with controls, among which primary BAs were elevated and secondary BAs were decreased. Moreover, distinct patterns of BA alterations were revealed between LUAD patients and LUSC patients.

The Value of Targeting CXCR4 With 68Ga-Pentixafor PET/CT for Subtyping Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) is one of the leading causes of secondary hypertension, and its diagnostic subtyping consistently presents a clinical challenge. OBJECTIVE: This study aimed to investigate the potential of 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) in PA classification and its applicability in guiding the development of clinical treatment plans by increasing the sample size. METHODS: We prospectively enrolled 120 patients with either PA or nonfunctional adenoma (NFA) for analysis. All patients underwent 68Ga-Pentixafor PET/CT. Of these, 11 patients underwent adrenal venous sampling (AVS), 77 underwent adrenalectomy, 76 received pathological diagnoses, and 71 underwent immunohistochemical detection of aldosterone synthase (CYP11B2). Immunohistochemistry for C-X-C chemokine receptor 4 (CXCR4) was performed in 62 cases. Follow-up was conducted for all patients. RESULTS: Among the 120 patients, 66 were diagnosed with aldosterone-producing adenoma (APA), 33 with idiopathic hyperaldosteronism (IHA), and 21 with NFA. For APA patients, the sensitivity, specificity, and accuracy of visual analysis using 68Ga-Pentixafor PET/CT were 92.40%, 94.40%, and 93.33%, respectively. Furthermore, for APA patients with a nodule greater than 1 cm in diameter, when the maximum standard uptake value was 7.3 or greater, the specificity was 100%; and for APA patients with a nodule less than 1 cm in diameter, 68Ga-Pentixafor PET/CT also exhibited high sensitivity. AVS was successfully performed in 5 patients. Among the 5 patients, the concordance rate between the AVS and 68Ga-Pentixafor PET/CT for PA subtyping was 60%. In the 77 patients who underwent adrenalectomy, 61 PET/CT scans displayed positive lesions, all of which benefited from the surgery. Additionally, the concordance rate between 68Ga-Pentixafor PET/CT imaging and CYP11B2 was 81.69%. CONCLUSION: 68Ga-Pentixafor PET/CT is a reliable and noninvasive functional imaging technique that demonstrates high accuracy in classifying PA and provides valuable guidance for clinical treatment decision-making.

Neural Stem Cell-Derived Exosomes Improve Neurological Function in Rats with Cerebral Ischemia-Reperfusion Injury by Regulating Microglia-Mediated Inflammatory Response.

Purpose: To investigate the effect of neural stem cell-derived exosomes (NSC-Exos) on neural function after rat cerebral ischemia-reperfusion injury by regulating microglia-mediated inflammatory response. Methods: SD rats were randomly divided into Sham group, IRI group, PBS group and NSC-Exos group. Each group was divided into 1d, 3d, 7d and 14d subgroups. In the Sham group, only cervical vessels were isolated without blockage. MCAO model was constructed in the other three groups by blocking middle cerebral artery with thread embolism. PBS group and NSC-Exos group were, respectively, injected into the lateral ventricle of PBS and Exos. Neurobehavioral deficit scores were performed for each subgroup at relative time points, then brains were taken for TTC staining, parietal cortex histopathology and microglia-mediated inflammatory response-related factors were detected. Results: Compared with Sham group, neurological defect score and infarction volume in both the IRI and PBS groups were significantly increased. The exploration target quadrant time and escape latency time of maze test were increased. The number of CD86+/Iba1+ double-positive cells increased, while CD206+/Iba1+ double-positive cells decreased. The expressions of IL-6 and CD86 in parietal cortex were increased, while the expressions of Arg1 and CD206 were decreased. Compared with the IRI group and PBS group, neurological defect score and infarction volume in NSC-Exos group were decreased. The exploration target quadrant time and escape latency time of water maze test were decreased. The number of CD206+/Iba1+ double-positive cells increased, while CD86+/Iba1+ double-positive cells decreased. The expressions of Arg1 and CD206 in parietal cortex were increased, while the expressions of IL-6 and CD86 were decreased. Conclusion: NSC-Exos can promote the polarization of microglia, that is, inhibit the polarization of M1 and promote polarization of M2, reduce microglia-mediated neuroinflammation, suggesting that NSC-Exos may be a strategy for the treatment of microglia-mediated neuroinflammation after ischemic brain injury.

Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2.

The pancreatic stellate cells (PSCs) play an important role in the development of pancreatic cancer (PC) through mechanisms that remain unclear. Exosomes secreted from PSCs act as mediators for communication in PC. This study aimed to explore the role of PSC-derived exosomal small RNAs derived from tRNAs (tDRs) in PC cells. Exosomes from PSCs were extracted and used to detect their effects on PC cell proliferation, migration and invasion. Exosomal tDRs profiling was performed to identify PSC-derived exosomal tDRs. ISH and qRT-PCR were used to examine the tRF-19-PNR8YPJZ levels and clinical value in clinical samples. The biological function of exosomal tRF-19-PNR8YPJZ was determined using the CCK-8, clone formation, wound healing and transwell assays, subcutaneous tumour formation and lung metastatic models. The relationship between the selected exosomal tRF-19-PNR8YPJZ and AXIN2 was determined by RNA sequencing, luciferase reporter assay. PSC-derived exosomes promoted the proliferation, migration, and invasion of PC cells. Novel and abundant tDRs are found to be differentially expressed in PANC-1 cells after treatment with PSC-derived exosomes, such as tRF-19-PNR8YPJZ. PC tissue samples showed markedly higher levels of tRF-19-PNR8YPJZ than normal controls. Patients with PC exhibiting high tRF-19-PNR8YPJZ expression had a highly lymph node invasion, metastasis, perineural invasion, advanced clinical stage and poor overall survival. Exosomal tRF-19-PNR8YPJZ from PSCs targeted AXIN2 in PC cells and decreased its expression, thus activating the Wnt pathway and promoting proliferation and metastasis. Exosomal tRF-19-PNR8YPJZ from PSCs promoted proliferation and metastasis in PC cells via AXIN2.

Development of two immunochromatographic test strips based on signal amplification and selenium nanoparticles for the rapid detection of T-2 mycotoxin.

Conventional immunochromatographic test strips (ICSs) based on gold nanoparticle (AuNP) probes offer limited sensitivity. Here, AuNPs were separately labeled with monoclonal or secondary antibodies (MAb or SAb). In addition, spherical, homogeneously dispersed, and stable selenium nanoparticles (SeNPs) were also synthesized. By optimizing the preparation parameters, two ICSs based on the dual AuNP signal amplification (Duo-ICS) or SeNPs (Se-ICS) were developed for the rapid detection of T-2 mycotoxin. The detection sensitivities of the Duo-ICS and Se-ICS assays for T-2 were 1 ng/mL and 0.25 ng/mL, respectively, which were 3-fold and 15-fold more sensitive, respectively, than a conventional ICS. Furthermore, the ICSs were applied in the detection of T-2 in cereals, which requires higher sensitivity. Our findings indicate that both ICS systems can be used for rapid, sensitive, and specific detection of T-2 toxin in cereals and potentially other sample types.

Synaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by SV2A Positron Emission Tomography.

BACKGROUND: Severe reduced synaptic density was observed in spinocerebellar ataxia (SCA) in postmortem neuropathology, but in vivo assessment of synaptic loss remains challenging. OBJECTIVE SPINOCEREBELLAR ATAXIA TYPE 3: The objective of this study was to assess in vivo synaptic loss and its clinical correlates in spinocerebellar ataxia type 3 (SCA3) patients by synaptic vesicle glycoprotein 2A (SV2A)-positron emission tomography (PET) imaging. METHODS: We recruited 74 SCA3 individuals including preataxic and ataxic stages and divided into two cohorts. All participants received SV2A-PET imaging using 18 F-SynVesT-1 for synaptic density assessment. Specifically, cohort 1 received standard PET procedure and quantified neurofilament light chain (NfL), and cohort 2 received simplified PET procedure for exploratory purpose. Bivariate correlation was performed between synaptic loss and clinical as well as genetic assessments. RESULTS: In cohort 1, significant reductions of synaptic density were observed in cerebellum and brainstem in SCA3 ataxia stage compared to preataxic stage and controls. Vermis was found significantly involved in preataxic stage compared to controls. Receiver operating characteristic (ROC) curves highlighted SV2A of vermis, pons, and medulla differentiating preataxic stage from ataxic stage, and SV2A combined with NfL improved the performance. Synaptic density was significantly negatively correlated with disease severity in cerebellum and brainstem (International Co-operative Ataxia Rating Scale: ρ ranging from -0.467 to -0.667, P ≤ 0.002; Scale of Assessment and Rating of Ataxia: ρ ranging from -0.465 to -0.586, P ≤ 0.002). SV2A reduction tendency of cerebellum and brainstem identified in cohort 1 was observed in cohort 2 with simplified PET procedure. CONCLUSIONS: We first identified in vivo synaptic loss was related to disease severity of SCA3, suggesting SV2A PET could be a promising clinical biomarker for disease progression of SCA3. © 2023 International Parkinson and Movement Disorder Society.

Molecular superglue-mediated higher-order assembly of TRAIL variants with superior apoptosis induction and antitumor activity.

Prompting higher-order death receptor (DR) clustering by increasing the valency of DR agonist is efficient to induce apoptosis of tumor cells. As an attractive DR agonist with superior biosafety, the trimeric tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts limited antitumor effect in patients, which is predominantly attributed to its low DR clustering ability and short serum half-life. Previous antibody scaffolds-based engineering strategies to increase the valency and/or prolong the serum half-life of TRAIL improve apoptosis induction, however, often produce large proteins with poor tumor penetration. Covalent protein ligation mediated by small molecular superglues such as SpyTag/SpyCatcher might be a novel strategy to assemble higher-order TRAIL variants. Upon fusion to TRAIL promotor, SpyTag/SpyCatcher molecular superglue preferentially ligated two trimeric TRAIL to produce a hexameric TRAIL variant, HexaTR, exhibiting a significantly increased apoptosis induction. In addition, an albumin-binding HexaTR, ABD-HexaTR, with a prolonged serum half-life by binding to endogenous albumin was also produced using the same strategy. Compared to the trimeric TRAIL, the hexameric HexaTR and ABD-HexaTR showed 20-50 times greater in vivo antitumor effect, resulting in eradication of several types of large (150-300 mm3) tumor xenografts. Combination with bortezomib carried by liposome further improved the antitumor effects of the hexavalent HexaTR and ABD-HexaTR in refractory cancer. Our results indicate that the superglue-mediated higher-order assembly is promising to improve the DR clustering and proapoptotic signaling of TRAIL, showing great advantages in constructing the next generation of DR agonists for cancer therapy.

Three-fluorescence sensor for minute-time scale low-cost analysis of urinary oxalate in urolithiasis metabolic assessment.

Since oxalate plays an important role in the metabolic assessment of urolithiasis, there is need for convenient and efficient methods for oxalate detection. Herein, we report a three-signal fluorescence strategy for oxalate analysis based on the ability of oxalate to reduce Cu2+ to Cu+, and the ability of pyrophosphate-cerium coordination polymeric networks (PPi-Ce CPNs), cadmium telluride quantum dots (CdTe QDs), and N-Methyl Mesoporphyrin (NMM) to selectively detect Cu2+ and Cu+. The detection range was 100 nM to 1 mM, the turnaround time was 6 min, while the limits of detections for PPi-Ce CPNs, QDs and NMM as reporters were 25 nM, 10 nM and 40 nM, respectively. Visual detection of oxalate relied on color change in the solution, which could be observed using the naked eye. The fluorescent system was used for oxalate analysis in 44 urine samples (32 calcium oxalate stone patients, 12 controls without urolithiasis), and the results were consistent with clinical diagnosis and imaging data. Moreover, the visual system was used to analyze 8 urine samples (4 patients and 4 controls), and showed good consistency with clinical diagnosis and computed tomography imaging results. These findings suggest that the method has potential application for the metabolic assessment of urolithiasis.

Serum untargeted metabolomics reveal metabolic alteration of non-small cell lung cancer and refine disease detection.

This study was performed to characterize the metabolic alteration of non-small-cell lung cancer (NSCLC) and discover blood-based metabolic biomarkers relevant to lung cancer detection. An untargeted metabolomics-based approach was applied in a case-control study with 193 NSCLC patients and 243 healthy controls. Serum metabolomics were determined by using an ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. We screened differential metabolites based on univariate and multivariate analysis, followed by identification of the metabolites and related pathways. For NSCLC detection, machine learning was employed to develop and validate the model based on the altered serum metabolite features. The serum metabolic pattern of NSCLC was definitely different from the healthy condition. In total, 278 altered features were found in the serum of NSCLC patients comparing with healthy people. About one-fifth of the abundant differential features were identified successfully. The altered metabolites were enriched in metabolic pathways such as phenylalanine metabolism, linoleic acid metabolism, and biosynthesis of bile acids. We demonstrated a panel of 10 metabolic biomarkers which representing excellent discriminating capability for NSCLC discrimination, with a combined area under the curve (AUC) in the validation set of 0.95 (95% CI: 0.91-0.98). Moreover, this model showed a desirable performance for the detection of NSCLC at an early stage (AUC = 0.95, 95% CI: 0.92-0.97). Our study offers a perspective on NSCLC metabolic alteration. The finding of the biomarkers might shed light on the clinical detection of lung cancer, especially for those cancers in an early stage in Chinese population.

Engineering Trichoderma reesei for the hyperproduction of cellulose induced protein 1 (Cip1) on a sophorose-containing inducer to efficiently saccharify alkali-pretreated corn stover.

Trichoderma reesei was induced to produce cellulase by a combination of glucose and ß-disaccharide; however, lower levels of auxiliary proteins for degrading lignocellulosic biomass were detected by iTRAQ analysis compared with cellulose as an inducer, especially cellulose induced protein 1 (CIP1). In this study, A pdc1 promoter-driven overexpression of the endogenous Trcip1 gene was observed in T. reesei Rut C30, and the Trcip1 transcription levels of the two transformants, T. reesei OE-cip1-1 and OE-cip1-2, demonstrated 31.2- and 164.6-fold increases, respectively, but there was no significant change in cellobiohydrolase, endoglucanase and filter paper activity at 48 h. The crude enzyme was then used to hydrolyze corn stover. For T. reesei OE-cip1-1 and OE-cip1-2, the hydrolysis efficiency increased by 25.0 and 28.6% with a solid loading of 5% at 2 h, respectively. Simultaneously, 85.5 and 85.2 g/L glucose were released using a cellulase cocktail at high solid loading (20%), and these glucose release rates were significantly greater than that of T. reesei Rut C30 cellulase (77.4 g/L) at 120 h. Furthermore, scanning electron microscopy (SEM) and X-ray diffraction (XRD) showed that the enhanced hydrolysis efficiency was primarily triggered by the decrease in the crystallinity of lignocellulose, and the fiber structure had varying degrees of loosening and disintegration.

Reduced levels of serum EPA and DHA identified in patients with non-small-cell lung cancer using a new rapid validated LC-MS/MS method.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to play roles in various diseases, yet there is little data on their changes in patients with non-small-cell lung cancer (NSCLC). A simple LC-MS/MS method for EPA and DHA determination is critical to exploring EPA and DHA level changes in NSCLC patients. METHODS: 25 µL of serum was mixed with 25 µL of internal standard working solution, and then 450 µL of acetonitrile for protein precipitation. After vortex and centrifugation, the supernatant was directly used for LC-MS/MS analysis. The method was well validated with linearity, precision, recovery, and matrix effect. The concentrations of EPA and DHA in serum samples from 211 NSCLC patients and 227 healthy controls were determined by this LC-MS/MS method. RESULTS: Good separation and reliable quantification of EPA and DHA in serum samples were achieved by our method. Compared with healthy controls, serum EPA and DHA were significantly reduced in both adenocarcinoma and squamous cell carcinoma patients. The concentrations of EPA and DHA showed a progressive decrease in healthy controls, early- and advanced-stage NSCLC patients. CONCLUSIONS: This study identified significant reductions in serum EPA and DHA in NSCLC patients through the development of an LC-MS/MS method.

Dietary fish and omega-3 polyunsaturated fatty acids intake and cancer survival: A systematic review and meta-analysis.

Fish and omega-3 polyunsaturated fatty acids (PUFA) have been suggested to play a role in improving cancer prognosis. However, results from epidemiological studies remain inconsistent. Here we assess the association between dietary fish and/or omega-3 PUFAs intake and cancer prognosis with meta-analysis of observational studies. A systematic search of related publications was performed using PubMed and Web of Science databases. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted and then pooled using a random-effect model. Potential linear and non-linear dose-response relationships were explored using generalized least squares estimation and restricted cubic splines. As a result, 21 cohort studies were included in our analysis. Compared to the lowest category, the highest category of fish intake was associated with a significant lower mortality in patients with ovarian cancer (n = 1, HR = 0.74, 95% CI: 0.57-0.95) and overall cancer (n = 12, HR = 0.87, 95% CI: 0.81-0.94). Marine omega-3 PUFAs intake rather than total omega-3 PUFAs intake showed significant protective effects on survival of overall cancer (n = 8, HR = 0.81, 95% CI: 0.71-0.94), in particular prostate cancer (n = 2, HR = 0.62, 95% CI: 0.46-0.82). Dose-response meta-analysis indicated a nonlinear and a linear relationship between fish intake, as well as marine omega-3 PUFAs intake, and overall cancer survival, respectively. In conclusion, our analysis demonstrated a protective effect of dietary fish and marine omega-3 PUFAs consumption on cancer survival.

Testosterone and soluble ST2 as mortality predictive biomarkers in male patients with sepsis-induced cardiomyopathy.

Sepsis-induced cardiomyopathy (SIC) is characterized by high mortality and poor outcomes. This study aimed to explore the relationship between testosterone and soluble ST2 (sST2) and all-cause mortality in patients with SIC. Clinical data from SIC patients at Renmin Hospital of Wuhan University from January 2021 and March 2023 were reviewed. Serum testosterone and sST2 were measured at admission. Kaplan-Meier analysis and receiver operative characteristic curve (ROC) were used to estimate the predictive values of testosterone and sST2 on 28 days and 90 days mortality of SIC. A total of 327 male subjects with SIC were enrolled in this study. During the 28 days and 90 days follow-up, 87 (26.6%) and 103 deaths (31.5%) occurred, respectively. Kaplan-Meier analysis showed significantly higher 28 days and 90 days survival in patients with higher testosterone and decreased sST2 levels (p < 0.001). Testosterone, sST2, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were significantly associated with 28 days and 90 days mortality (p < 0.05). Partial correlation analysis showed strong positive correlation between testosterone and left ventricular ejection fraction (LVEF) (p < 0.001), and negative correlation between testosterone and sST2 (p < 0.001), high-sensitivity troponin I (hs-TnI) levels (p < 0.001) and smoke history (p < 0.01). The concentrations of sST2 were positively related with E/e' ratio (p < 0.001), and negatively correlated with TAPSE (p < 0.001). The combination of testosterone and sST2 enhanced the prediction of both 28 days [area under the ROC curve (AUC), 0.805] and 90 days mortality (AUC, 0.833). Early serum testosterone and sST2 levels could predict mortality of SIC independently and jointly. Further research is needed to determine the utility of biochemical markers in identifying high-risk patients with SIC.

Artificially Sweetened Beverage Consumption and Cancer Risk: A Comprehensive Dose-Response Meta-Analysis of Prospective Studies.

The impact of artificially sweetened beverages (ASBs), alternatives to sugar-sweetened beverages, on cancer incidence remains controversial. We conducted a meta-analysis of prospective studies to assess the association of daily ASB intake with cancer risk. A systematic search was performed between January 1967 and September 2022. Risk ratios (RR) or hazard ratios (HR) were extracted and pooled. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used for the assessment of the certainty of evidence. The study was registered at PROSPERO (CRD42022312171). Overall, 14 articles with 17 cohorts were included. There was no significant association between daily ASB consumption and risk of overall cancer (highest versus lowest category: n = 17, RR = 1.03, 95% CI: 0.96-1.11, p = 0.407). For site-specific cancer analysis, the risk of non-lymphoid leukemia was elevated with high ASB intake (n = 3, RR = 1.35, 95% CI: 1.03-1.77, p = 0.030), while risk of colorectal cancer was decreased (n = 3, RR = 0.78, 95% CI: 0.62-0.99, p = 0.037). Dose-response analysis indicated a positive linear association between ASB intake and the risk of leukemia (p-linear = 0.027). The risk increased by 15% per one serving (355 mL) daily ASB intake increment (RR = 1.15, 95% CI: 1.02-1.30). In conclusion, ASB consumption might be positively associated with the risk of leukemia and negatively associated with the risk of colorectal cancer.

Changes in serum amino acid levels in non-small cell lung cancer: a case-control study in Chinese population.

Background: Previous studies have shown the alteration of amino acid (AA) profile in patients with non-small cell lung cancer (NSCLC). However, there is little data regarding AA profile in NSCLC in Chinese population. The aim of this study was to evaluate AA profile in Chinese NSCLC patients, explore its utility in sample classification and further discuss its related metabolic pathways. Methods: The concentrations of 22 AAs in serum samples from 200 patients with NSCLC and 202 healthy controls were determined by liquid chromatography-tandem mass spectrometer (LC-MS/MS). AA levels in different tumor stages and histological types were also discussed. The performance of AA panel in classifying the cases and controls was evaluated in the training data set and validation data set based on the receiver operating characteristic (ROC) curve, and the important metabolic pathways were identified. Results: The concentrations of tryptophan (Trp), phenylalanine (Phe), isoleucine (Ile), glycine (Gly), serine (Ser), aspartic acid (Asp), asparagine (Asn), cystein (Cys), glutamic acid (Glu), ornithine (Orn) and citrulline (Cit) were significantly altered in NSCLC patients compared with controls (all P-FDR < 0.05). Among these, four AAs including Asp, Cys, Glu and Orn were substantially up-regulated in NSCLC patients (FC ≥ 1.2). AA levels were significantly altered in patients with late-stage NSCLC, but not in those with early-stage when comparing with healthy controls. In terms of histological type, these AAs were altered in both adenocarcinoma and squamous cell carcinoma. For discrimination of NSCLC from controls, the area under the ROC curve (AUC) was 0.80 (95% CI [0.74-0.85]) in the training data set and 0.79 (95%CI [0.71-0.87]) in the validation data set. The AUCs for early-stage and late-stage NSCLC were 0.75 (95% CI [0.68-0.81]) and 0.86 (95% CI [0.82-0.91]), respectively. Moreover, the model showed a better performance in the classification of squamous cell carcinoma (AUC = 0.90, 95% CI [0.85-0.95]) than adenocarcinoma (AUC = 0.77, 95% CI [0.71-0.82]) from controls. Three important metabolic pathways were involved in the alteration of AA profile, including Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism; and Arg biosynthesis. Conclusions: The levels of several AAs in serum were altered in Chinese NSCLC patients. These altered AAs may be utilized to classify the cases from the controls. Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism and Arg biosynthesis pathways may play roles in metabolism of the NSCLC patient.

The Potential Prognostic Value of Dual-Imaging PET Parameters Based on 18F-FDG and 18F-OC for Neuroendocrine Neoplasms.

Background: To identify parameters based on dual-imaging 18F-AlF-NOTA-octreotide (18F-OC) and 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) for predicting the prognosis of neuroendocrine neoplasms (NENs). Materials and Methods: Sixty-six patients (age: mean ± standard deviation (SD): 51.8 ± 11.8 years) who underwent both 18F-OC and 18F-FDG PET/CT imaging were enrolled in our retrospective study. The following PET parameters were measured: the maximum standardized uptake value (SUVmax) and the volumetric parameters-18F-OC SSR-derived tumor volume (TV) and somatostatin receptor expression (SRE, TV multiplied by the mean standardized uptake value (SUVmean)) and the 18F-FDG-derived multiple tumor volume (MTV) and tumor lesion glycolysis (TLG). The NETPET grade based on dual-imaging PET images was assessed. Progression-free survival (PFS) was set as an endpoint. Univariate and multivariate survival analyses were performed for PET parameters and clinical tumor data. Results: In the univariate survival analyses of clinical information, PFS was significantly associated with age (>45.5 vs ≤45.5, years, P < 0.034) and the presence of bone metastases (P = 0.04). Higher values for the 18F-FDG and 18F-OC volumetric parameters and the NETPET grade were adverse factors for PFS according to the dual-imaging PET parameters. In the multivariate survival analysis, the NETPET grade and SRE were predictors of PFS in NEN patients. Conclusion: The NETPET grade is a potential noninvasive prognostic biomarker for NENs.

Cortical abnormalities of synaptic vesicle protein 2A in focal cortical dysplasia type II identified in vivo with 18F-SynVesT-1 positron emission tomography imaging.

PURPOSE: The loss of synaptic vesicle glycoprotein 2A (SV2A) is well established as the major correlate of epileptogenesis in focal cortical dysplasia type II (FCD II), but this has not been directly tested in vivo. In this positron emission tomography (PET) study with the new tracer 18F-SynVesT-1, we evaluated SV2A abnormalities in patients with FCD II and compared the pattern to 18F-fluorodeoxyglucose (18F-FDG). METHODS: Sixteen patients with proven FCD II and 16 healthy controls were recruited. All FCD II patients underwent magnetic resonance imaging (MRI) and static PET imaging with both 18F-SynVesT-1 and 18F-FDG, while the controls underwent MRI and PET with only 18F-SynVesT-1. Visual assessment of PET images was undertaken. The standardized uptake values (SUVs) of 18F-SynVesT-1 were computed for regions of interest (ROIs), along with SUV ratio (SUVr) between ROI and centrum semiovale (white matter). Asymmetry indices (AIs) were analyzed between the lesion and the contralateral hemisphere for intersubject comparisons. RESULTS: Lesions in the brains of FCD II patients had significantly reduced 18F-SynVesT-1 uptake compared with contralateral regions, and brains of the controls. 18F-SynVesT-1 PET indicated low lesion uptake in 14 patients (87.5%), corresponding to hypometabolism detected by 18F-FDG PET, with higher accuracy for lesion localization than MRI (43.8%) (P < 0.05). AI analyses demonstrated that in the lesions, SUVr for each of the radiotracers were not significantly different (P > 0.05), and 18F-SynVesT-1 SUVr correlated with that of 18F-FDG across subjects (R2 = 0.41, P = 0.008). Subsequent visual ratings indicated that 18F-SynVesT-1 uptake had a more restricted pattern of reduction than 18F-FDG uptake in FCD II lesions (P < 0.05). CONCLUSION: SV2A PET with 18F-SynVesT-1 shows a higher accuracy for the localization of FCD II lesions than MRI and a more restricted pattern of abnormality than 18F-FDG PET.