11C-CFT PET brain imaging in Parkinson's disease using a total-body PET/CT scanner.

PURPOSE: This study aimed to evaluate the feasibility of 11C-CFT PET brain imaging in Parkinson's Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice. METHODS: Thirty-two patients with Parkinson's disease (PD) performing 11C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference. RESULTS: The overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P < 0.05). However, all G300 image quality was clinically acceptable (≥ 3 points). As the scan duration reduced, the SUVmean and DAT binding of caudate nucleus and putamen decreased progressively, while there were no statistically significant variations in the SUVmean of the background among the different groups. Moreover, the changes in the lesion DAT binding (ΔDAT-binding) between the full-time reference G900 image and other reconstructed group G720 to G30 images generally increased along with the reduced scan time. CONCLUSION: Sufficient image quality and lesion conspicuity could be achieved at 600-s scan duration for 11C-CFT PET brain imaging in PD assessment using a total-body PET/CT scanner, while the image quality of G300 was acceptable to meet clinical diagnosis, contributing to improve patient compliance and throughput of PET brain imaging.

Metformin improves diabetic neuropathy by reducing inflammation through up-regulating the expression of miR-146a and suppressing oxidative stress.

PURPOSE: Diabetic neuropathy (DN) is a notable complication of diabetes mellitus. The potential involvement of miR-146a in DN regulation is presently under investigation. Metformin, a commonly prescribed medication for diabetes, is the primary therapeutic intervention. This study aimed to unveil the potential protective effects of metformin on diabetic neuropathy and explore the mechanisms underlying its action. METHOD: Six-weeks male Sprague Dawley rats (n = 40) were randomly divided into 5 groups. The rat model of diabetic neuropathy (DN) was established by administering streptozotocin (STZ). To investigate the effects on the sciatic nerve and resident Schwann cells (RSCs), metformin and miR-146a mimics were administered, and our research explored the potential underlying mechanism. RESULT: The sciatic nerve samples obtained from diabetic rats exhibited noticeable morphological damage, accompanied by decreased miR-146a expression (2.61 ± 0.11 vs 5.0 ± 0.3, p < 0.01) and increased inflammation levels (p65: 1.89 ± 0.04 vs 0.82 ± 0.05, p < 0.01; TNF-α: 0.93 ± 0.03 vs 0.33 ± 0.03, p < 0.01). Notably, the administration of metformin effectively ameliorated the structural alterations in the sciatic nerve by suppressing the inflammatory pathway (p65: 1.15 ± 0.05 vs 1.89 ± 0.04, p < 0.01; TNF-α: 0.67 ± 0.04 vs 0.93 ± 0.03, p < 0.01) and reducing oxidative stress (NO: 0.062 ± 0.004 vs 0.154 ± 0.004umol/mg, p < 0.01; SOD: 3.08 ± 0.09 vs 2.46 ± 0.09 U/mg, p < 0.01). The miR-146a mimics intervention group exhibited comparable findings. CONCLUSION: This study's findings implied that metformin can potentially mitigate diabetic neuropathy in rats through the modulation of miR-146a expression.

Genomic and Phenotypic Analysis of Salmonella enterica Bacteriophages Identifies Two Novel Phage Species.

Bacteriophages (phages) are potential alternatives to chemical antimicrobials against pathogens of public health significance. Understanding the diversity and host specificity of phages is important for developing effective phage biocontrol approaches. Here, we assessed the host range, morphology, and genetic diversity of eight Salmonella enterica phages isolated from a wastewater treatment plant. The host range analysis revealed that six out of eight phages lysed more than 81% of the 43 Salmonella enterica isolates tested. The genomic sequences of all phages were determined. Whole-genome sequencing (WGS) data revealed that phage genome sizes ranged from 41 to 114 kb, with GC contents between 39.9 and 50.0%. Two of the phages SB13 and SB28 represent new species, Epseptimavirus SB13 and genera Macdonaldcampvirus, respectively, as designated by the International Committee for the Taxonomy of Viruses (ICTV) using genome-based taxonomic classification. One phage (SB18) belonged to the Myoviridae morphotype while the remaining phages belonged to the Siphoviridae morphotype. The gene content analyses showed that none of the phages possessed virulence, toxin, antibiotic resistance, type I-VI toxin-antitoxin modules, or lysogeny genes. Three (SB3, SB15, and SB18) out of the eight phages possessed tailspike proteins. Whole-genome-based phylogeny of the eight phages with their 113 homologs revealed three clusters A, B, and C and seven subclusters (A1, A2, A3, B1, B2, C1, and C2). While cluster C1 phages were predominantly isolated from animal sources, cluster B contained phages from both wastewater and animal sources. The broad host range of these phages highlights their potential use for controlling the presence of S. enterica in foods.

Infectivity responses of Salmonella enterica to bacteriophages on maize seeds and maize sprouts.

Salmonella enterica (S. enterica) is a major foodborne pathogen leading to a large number of outbreaks and bringing food safety concerns to sprouts. The control of S. enterica on maize sprouts is important because raw maize sprouts have been gaining attention as a novel superfood. Compared to conventional chemical methods, the applications of bacteriophages are regarded as natural and organic. This study investigated the effects of a 2 h phage cocktail (SF1 and SI1, MOI 1000) soaking on reducing the populations of three Salmonella enterica strains: S. Enteritidis S5-483, S. Typhimurium S5-536, and S. Agona PARC5 on maize seeds and during the storage of maize sprouts. The results showed that the phage cocktail treatment effectively reduced populations of S. enterica strains by 1-3 log CFU/g on maize seeds and decreased population of S. Agona PACR5 by 1.16 log CFU/g on maize sprouts from 7.55 log CFU/g at day 0 of the storage period. On the other hand, the upregulations of flagella gene pefA by 1.5-folds and membrane gene lpxA by 23-folds in S. Typhimurium S5-536 indicated a differential response to the phage cocktail treatment. Conversely, stress response genes ompR, rpoS, and recA, as well as the DNA repair gene yafD, were downregulated in S. Agona PARC5. This work shows the use of bacteriophages could contribute as a part of hurdle effect to reduce S. enterica populations and is beneficial to develop strategies for controlling foodborne pathogens in the production and storage of maize sprouts.

Inactivation of Salmonella enteritidis in liquid egg yolk and egg white using bacteriophage cocktails.

Salmonella Enteritidis (SE) is a significant global cause of foodborne illness, often linked to egg contamination. This study evaluated the inhibitory effects of eight bacteriophages (phages) against three SE strains isolated from poultry environments. The most effective phages were selected to formulate different phage cocktails, to enhance the efficacy and prolong inhibition. Four phage cocktails were tested at a multiplicity of infection (MOI) of 100 in tryptic soy broth (TSB), and at MOIs of 100 and 1000 in liquid egg white (EW) and egg yolk (EY) with storage at 8 °C for up to 30 days (d). The effectiveness of the phage cocktails varied significantly among bacterial strains, yet all demonstrated significant reductions compared to the positive control in liquid culture (P < 0.05). Similarly, the tested SE strains in both EW and EY showed significant reductions with phage treatments (P < 0.005), although the effectiveness was influenced by the MOI and medium composition. Treating EY proved to be more challenging, with lower magnitudes of reduction and longer treatment durations required, compared to EW. Reductions ranged from 1 to greater than 4 log CFU/mL in EW and EY after 30 d, with consistently higher reductions achieved at MOI 1000. Phage titers decreased initially, but remained stable following SE inoculation in broth and liquid eggs at 8 °C, indicating that lysis from without mechanisms may have contributed to the inhibitory effect. Notably, phages exhibited stronger attachment to SE in EW, which can be attributed to be less viscous nature of EW compared to EY. This study demonstrated that phage applications in both EW and EY effectively reduced SE counts at 8 °C, with no regrowth during long-term storage. These findings contribute to the development of biocontrol methods that enhance food safety and reduce foodborne outbreaks associated with contaminated egg products.

Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease.

AIM: The retina and brain share similar anatomical and physiological features. Thus, retinal imaging by optical coherence tomography angiography (OCTA) might be a potential tool for the early diagnosis of diabetic cerebral small vessel disease (CSVD). In this study, we aimed to evaluate retinal vascular density (VD) in diabetic CSVD by OCTA imaging and explore the associations between retinal VD and cerebral magnetic resonance imaging (MRI) markers and cognitive function. METHODS: In total, 131 patients were enrolled, including CSVD (n = 43) and non-CSVD groups (n = 88). The VD and foveal avascular zone of the retinal capillary plexus were measured with OCTA. A brain MRI was performed. RESULTS: MRI imaging showed that in the diabetic CSVD group, white matter hyperintensities (WMHs), particularly deep WMHs (58.82%), are the most common MRI marker, followed by cerebral microbleeds in the subtentorial and cortical areas (34.78%). The CSVD group showed increases in the prevalence of cognitive dysfunction (p = .034) and depression (p = .033) and decreases in visuospatial/executive ability and delayed recall ability. In the CSVD group, VDs of the macular superficial vascular plexus (32.93 ± 7.15% vs. 36.97 ± 6.59%, p = .002), intermediate capillary plexus (20.87 ± 4.30% vs. 23.08 ± 4.30%, p = .005) and deep capillary plexus (23.54 ± 5.00% vs. 26.05 ± 4.20%, p = .003) were lower than those of the non-CSVD group. Multiple linear regression analysis showed that VD of the macular superficial vascular plexus was independently associated with cerebral microbleeds. Meanwhile, VD of the macular intermediate capillary plexus was associated with white matter lacunar infarcts after adjustment. CONCLUSIONS: Diabetic CSVDs are characterized by MRI markers, including deep WMHs and cerebral microbleeds, and showed impaired cognition with decreased visuospatial/executive ability and delayed recall ability. OCTA imaging revealed a significant decrease in retinal microvascular perfusion in diabetic CSVD, which was related to MRI markers and cognitive function. OCTA might be a valuable potential measurement for the early diagnosis of CSVD.

Urinary Endometriosis Misdiagnosed as Ureteral Malignant Tumor by PET/CT: A Case Study.

ABSTRACT: Endometriosis is a chronic inflammatory estrogen-dependent benign disease. It is defined as the endometrium growing outside the uterine cavity and the myometrium. It usually has low FDG uptake but rarely occurs in the ureters. We reported a case of a 47-year-old woman's left ureteral nodule originally misdiagnosed as a ureteral malignant tumor by PET/CT and finally pathologically confirmed as endometriosis.

Evaluation of the impact of repeated intravenous phage doses on mammalian host-phage interactions.

Phage therapy has shown great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.IMPORTANCEPhage therapy has demonstrated potential in addressing multidrug-resistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes.

Pharmacokinetics and safety evaluation of intravenously administered Pseudomonas phage PA_LZ7 in a mouse model.

IMPORTANCE: Phage therapy is gaining traction as an alternative to antibiotics due to the rise of multi-drug-resistant (MDR) bacteria. This study assessed the pharmacokinetics and safety of PA_LZ7, a phage targeting MDR Pseudomonas aeruginosa, in mice. After intravenous administration, the phage showed an exponential decay in plasma and its concentration dropped significantly within 24 h for all dosage groups. Although there was a temporary increase in certain plasma cytokines and spleen weight at higher dosages, no significant toxicity was observed. Therefore, PA_LZ7 shows potential as an effective and safe candidate for future phage therapy against MDR P. aeruginosa infections.

Reduction of Nontyphoidal Salmonella enterica in Broth and on Raw Chicken Breast by a Broad-spectrum Bacteriophage Cocktail.

Globally, nontyphoidal Salmonella (NTS) causes approximately 150 million foodborne illnesses annually; many of which are linked to poultry products. Thus, improving food safety interventions in the poultry sector can reduce foodborne illness associated with prevalent NTS serotypes. Bacteriophages (phages) have shown promise as food-safe alternatives to current antimicrobial practices. However, challenges such as limited host range, bactericidal effectiveness in practical production settings, and the risk of developing host resistance remain as barriers for the widespread use of phages in commercial poultry operations. A broad-spectrum three-phage cocktail was evaluated against S. enterica subsp. enterica serotypes Enteritidis, Typhimurium, and Kentucky. The impact of multiplicity of infection (MOI) on NTS growth was assessed in broth at 22°C for 18 hours (h). Then, phage cocktail efficacy was evaluated on raw chicken breast samples inoculated with the NTS cocktail and stored at 10°C or 22°C for 0, 1, and 5 days or 0, 4, 8, and 16 h, respectively. Most probable number (MPN) calculations were performed for NTS counts on chicken after phage treatment and storage at 10°C to account for samples with NTS counts below the detection limit. In general, a higher MOI corresponded to reduced NTS growth; however, residual nutrition in growth media and initial NTS contamination level affected samples treated with the phage cocktail at identical MOIs. On chicken, phage cocktail treatment significantly reduced NTS counts at 10°C and 22°C. After storage at 10°C for 5 days, NTS counts were reduced by >3.2 log compared to the control. After storage at 22°C for 16 h, NTS counts were reduced by >1.7 log compared to the control. Overall, the phage cocktail was effective at reducing a diverse set of prominent NTS strains in broth and on raw chicken breast, highlighting its potential for commercialization and use alongside other hurdles in poultry production.

Pretreatment radiomic biomarker for immunotherapy responder prediction in stage IB-IV NSCLC (LCDigital-IO Study): a multicenter retrospective study.

BACKGROUND: The predictive efficacy of current biomarker of immune checkpoint inhibitors (ICIs) is not sufficient. This study investigated the causality between radiomic biomarkers and immunotherapy response status in patients with stage IB-IV non-small cell lung cancer (NSCLC), including its biological context for ICIs treatment response prediction. METHODS: CT images from 319 patients with pretreatment NSCLC receiving immunotherapy between January 2015 and November 2021 were retrospectively collected and composed a discovery (n=214), independent validation (n=54), and external test cohort (n=51). A set of 851 features was extracted from tumorous and peritumoral volumes of interest (VOIs). The reference standard is the durable clinical benefit (DCB, sustained disease control for more than 6 months assessed via radiological evaluation). The predictive value of combined radiomic signature (CRS) for pathological response was subsequently assessed in another cohort of 98 patients with resectable NSCLC receiving ICIs preoperatively. The association between radiomic features and tumor immune landscape on the online data set (n=60) was also examined. A model combining clinical predictor and radiomic signatures was constructed to improve performance further. RESULTS: CRS discriminated DCB and non-DCB patients well in the training and validation cohorts with an area under the curve (AUC) of 0.82, 95% CI: 0.75 to 0.88, and 0.75, 95% CI: 0.64 to 0.87, respectively. In this study, the predictive value of CRS was better than programmed cell death ligand-1 (PD-L1) expression (AUC of PD-L1 subset: 0.59, 95% CI: 0.50 to 0.69) or clinical model (AUC: 0.66, 95% CI: 0.51 to 0.81). After combining the clinical signature with CRS, the predictive performance improved further with an AUC of 0.837, 0.790 and 0.781 in training, validation and D2 cohorts, respectively. When predicting pathological response, CRS divided patients into a major pathological response (MPR) and non-MPR group (AUC: 0.76, 95% CI: 0.67 to 0.81). Moreover, CRS showed a promising stratification ability on overall survival (HR: 0.49, 95% CI: 0.27 to 0.89; p=0.020) and progression-free survival (HR: 0.43, 95% CI: 0.26 to 0.74; p=0.002). CONCLUSION: By analyzing both tumorous and peritumoral regions of CT images in a radiomic strategy, we developed a non-invasive biomarker for distinguishing responders of ICIs therapy and stratifying their survival outcome efficiently, which may support the clinical decisions on the use of ICIs in advanced as well as patients with resectable NSCLC.

Insights into tissue-specific anthocyanin accumulation in Japanese plum (Prunus salicina L.) fruits: A comparative study of three cultivars.

In the present study, three matured Japanese plum cultivars with different colored peel and flesh were selected to mine the key transcription factors regulating anthocyanin formation in tissues. Results showed that PsMYB10 was correlated with structural genes C4H, F3H, and ANS. PsMYB6 could positively regulate C4H (r = 0.732) and accumulated anthocyanins in Sanhua plum's flesh. Sanhua plum has the highest phenolic and anthocyanin contents (10.24 ± 0.37 gallic acid equivalent mg g-1 dry weight (DW) and 68.95 ± 1.03 µg g-1 DW), resulting itself superior biological activity as 367.1 ± 42.9 Trolox equivalent mg g-1 DW in oxygen radical absorbance capacity value and 72.79 ± 4.34 quercetin equivalent mg g-1 DW in cellular antioxidant activity value. The present work provides new insights into the regulatory mechanism of tissue-specific anthocyanin biosynthesis, confirming the pivotal role of anthocyanins in the biological activity of plums, providing essential support for the development of horticultural products enriched with anthocyanins.

Future self-continuity and depression among college students: The role of presence of meaning and perceived social support.

INTRODUCTION: Future self-continuity has been shown to have a protective effect against depression. This study aims to investigate the longitudinal relationship between future self-continuity and depression among college students, and to explore the mediating role of the presence of meaning and the moderating role of perceived social support. METHODS: We conducted two studies in China in 2022 and 2023. Study 1 was a longitudinal cross-lagged study that examined the relationship between future self-continuity and depression among 173 participants (49.13% females, Mage = 19.39, SD = 1.63). Study 2 was a cross-sectional study that explored the mediating role of the presence of meaning and the moderating role of perceived social support among 426 participants (48.59% females, Mage = 19.30, SD = 1.60). RESULTS: Study 1 showed that future self-continuity (T1) could significantly predict depression (T2), but depression (T1) could not predict future self-continuity (T2). Study 2 showed that after controlling for gender, the presence of meaning mediated the relationship between future self-continuity and depression, whereas perceived social support moderated the first half of the mediated model's pathway and the direct pathway. CONCLUSIONS: These findings suggest that enhancing the future self-continuity of college students and increasing the level of presence of meaning are effective measures for alleviating depression. Meanwhile, educators and families are called upon to provide more social support to college students.

The Effect of Oral Iron Supplementation on Gut Microbial Composition: a Secondary Analysis of a Double-Blind, Randomized Controlled Trial among Cambodian Women of Reproductive Age.

The World Health Organization recommends untargeted iron supplementation for women of reproductive age (WRA) in countries where anemia prevalence is greater than 40%, such as Cambodia. Iron supplements, however, often have poor bioavailability, so the majority remains unabsorbed in the colon. The gut houses many iron-dependent bacterial enteropathogens; thus, providing iron to individuals may be more harmful than helpful. We examined the effects of two oral iron supplements with differing bioavailability on the gut microbiomes in Cambodian WRA. This study is a secondary analysis of a double-blind, randomized controlled trial of oral iron supplementation in Cambodian WRA. For 12 weeks, participants received ferrous sulfate, ferrous bisglycinate, or placebo. Participants provided stool samples at baseline and 12 weeks. A subset of stool samples (n = 172), representing the three groups, were randomly selected for gut microbial analysis by 16S rRNA gene sequencing and targeted real-time PCR (qPCR). At baseline, 1% of women had iron-deficiency anemia. The most abundant gut phyla were Bacteroidota (45.7%) and Firmicutes (42.1%). Iron supplementation did not alter gut microbial diversity. Ferrous bisglycinate increased the relative abundance of Enterobacteriaceae, and there was a trend towards an increase in the relative abundance of Escherichia-Shigella. qPCR detected an increase in the enteropathogenic Escherichia coli (EPEC) virulence gene, bfpA, in the group that received ferrous sulfate. Thus, iron supplementation did not affect overall gut bacterial diversity in predominantly iron-replete Cambodian WRA, however, evidence does suggest an increase in relative abundance within the broad family Enterobacteriaceae associated with ferrous bisglycinate use. IMPORTANCE To the best of our knowledge, this is the first published study to characterize the effects of oral iron supplementation on the gut microbiomes of Cambodian WRA. Our study found that iron supplementation with ferrous bisglycinate increases the relative abundance of Enterobacteriaceae, which is a family of bacteria that includes many Gram-negative enteric pathogens like Salmonella, Shigella, and Escherichia coli. Using qPCR for additional analysis, we were able to detect genes associated with enteropathogenic E. coli, a type of diarrheagenic E. coli known to be present around the world, including water systems in Cambodia. The current WHO guidelines recommend blanket (untargeted) iron supplementation for Cambodian WRA despite a lack of studies in this population examining iron's effect on the gut microbiome. This study can facilitate future research that may inform evidence-based global practice and policy.

Circ_0003028 enhances the proliferation and glycolytic capacity and suppresses apoptosis in non-small cell lung cancer cells via the miR-1305/miR-1322-SLC5A1 axis.

Background: Circular RNA (circRNA), a unique RNA molecule with a circular structure, is relevant to the process of non-small cell lung cancer (NSCLC). However, the role and possible mechanisms of circ_0003028 in NSCLC are not completely clear. Here, we investigated the role of circ_0003028 in NSCLC progression. Methods: We first confirmed the stability and head-to-tail junction sequences of circ_000302. Circ_0003028 expression was identified with quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC tissues, and the survival probability and prognosis were analyzed using Kaplan-Meier survival and receiver operating characteristic (ROC) analyses. Functionally, the proliferation, apoptosis, and glycolytic capacity were examined using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, a flow cytometer, commercial kits [glucose, lactate, and adenosine triphosphate (ATP)], and a Seahorse XF extracellular flux analyzer. Moreover, the potential microRNAs (miRNAs) of circ_0003028 were predicted and identified, and the target gene of miRNA (miR)-1322 and miR-1305 were also screened using DIANA-microT and TargetScan. Results: We first determined the head-to-tail junction sequences of circ_0003028 and its stability. Circ_0003028 was also confirmed to be upregulated in NSCLC tissues. Meanwhile, circ_0003028 had poor overall survival and high diagnostic potential in NSCLC patients. Furthermore, we found that overexpression of circ_0003028 could increase the proliferation and glycolytic capacity and restrain the apoptosis of NSCLC cells, and circ_0003028 silencing played the opposite role to circ_0003028 overexpression. Moreover, circ_0003028 might regulate miR-1305 and miR-1322, which might further regulate solute carrier family 5 member 1 (SLC5A1). Conclusions: Circ_0003028 could accelerate the malignant behaviors and glycolytic capacity of NSCLC cells via a mechanism that may be related to miR-1305 or the miR-1322/SLC5A1 axis. Therefore, the findings of the current study provide a preliminary theoretical basis for NSCLC therapy and diagnosis.

Microbiome and Physicochemical Features Associated with Differential Listeria monocytogenes Growth in Soft, Surface-Ripened Cheeses.

Soft-ripened cheeses (SRCs) are at a higher risk for the growth of the foodborne pathogen Listeria monocytogenes due to favorable moisture content and pH compared to other cheeses. L. monocytogenes growth is not consistent across SRCs, however, and may be affected by physicochemical and/or microbiome characteristics of the cheeses. Therefore, the purpose of this study was to investigate how the physicochemical and microbiome profiles of SRCs may affect L. monocytogenes growth. Forty-three SRCs produced from raw (n = 12) or pasteurized (n = 31) milk were inoculated with L. monocytogenes (103 CFU/g), and the pathogen growth was monitored over 12 days at 8°C. In parallel, the pH, water activity (aw), microbial plate counts, and organic acid content of cheeses were measured, and the taxonomic profiles of the cheese microbiomes were measured using 16S rRNA gene targeted amplicon sequencing and shotgun metagenomic sequencing. L. monocytogenes growth differed significantly between cheeses (analysis of variance [ANOVA]; P < 0.001), with increases ranging from 0 to 5.4 log CFU (mean of 2.5 ± 1.2 log CFU), and was negatively correlated with aw. Raw milk cheeses showed significantly lower L. monocytogenes growth than pasteurized-milk cheeses (t test; P = 0.008), possibly due to an increase in microbial competition. L. monocytogenes growth in cheeses was positively correlated with the relative abundance of Streptococcus thermophilus (Spearman correlation; P < 0.0001) and negatively correlated with the relative abundances of Brevibacterium aurantiacum (Spearman correlation; P = 0.0002) and two Lactococcus spp. (Spearman correlation; P < 0.01). These results suggest that the cheese microbiome may influence the food safety in SRCs. IMPORTANCE Previous studies have identified differences in L. monocytogenes growth between SRCs, but no clear mechanism has yet been elucidated. To the best of our knowledge, this is the first study to collect a wide range of SRCs from retail sources and attempt to identify key factors associated with pathogen growth. A key finding in this research was the positive correlation between the relative abundance of S. thermophilus and the growth of L. monocytogenes. The inclusion of S. thermophilus as a starter culture is more common in industrialized SRC production, suggesting that industrial production of SRC may increase the risk of L. monocytogenes growth. Overall, the results of this study further our understanding of the impact of aw and the cheese microbiome on the growth of L. monocytogenes in SRCs, hopefully leading toward the development of SRC starter/ripening cultures that can prevent L. monocytogenes growth.

Artificial intelligence-based computer-aided diagnosis system supports diagnosis of lymph node metastasis in esophageal squamous cell carcinoma: A multicenter study.

Background: This study aimed to develop an artificial intelligence-based computer-aided diagnosis system (AI-CAD) emulating the diagnostic logic of radiologists for lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) patients, which contributed to clinical treatment decision-making. Methods: A total of 689 ESCC patients with PET/CT images were enrolled from three hospitals and divided into a training cohort and two external validation cohorts. 452 CT images from three publicly available datasets were also included for pretraining the model. Anatomic information from CT images was first obtained automatically using a U-Net-based multi-organ segmentation model, and metabolic information from PET images was subsequently extracted using a gradient-based approach. AI-CAD was developed in the training cohort and externally validated in two validation cohorts. Results: The AI-CAD achieved an accuracy of 0.744 for predicting pathological LNM in the external cohort and a good agreement with a human expert in two external validation cohorts (kappa = 0.674 and 0.587, p < 0.001). With the aid of AI-CAD, the human expert's diagnostic performance for LNM was significantly improved (accuracy [95% confidence interval]: 0.712 [0.669-0.758] vs. 0.833 [0.797-0.865], specificity [95% confidence interval]: 0.697 [0.636-0.753] vs. 0.891 [0.851-0.928]; p < 0.001) among patients underwent lymphadenectomy in the external validation cohorts. Conclusions: The AI-CAD could aid in preoperative diagnosis of LNM in ESCC patients and thereby support clinical treatment decision-making.

Lysine-Derived Maillard Reaction Products Inhibit the Growth of Salmonella enterica Serotype Typhimurium.

An emerging consumer trend to purchase minimally heated and ready-to-eat food products may result in processing methods that do not effectively reduce pathogenic populations. Crude Maillard reaction products (MRPs) are naturally generated compounds that have been shown to display antimicrobial effects against pathogens. Crude MRPs were generated from reducing sugars (fructose (Fru), glucose (Glc), ribose (Rib) or xylose (Xyl)) with lysine and the melanoidin equivalence was measured using an absorbance of 420 nm (Ab420). The relative antimicrobial activity of each MRP was measured by examining both the length of lag phase and maximum growth rate. MRPs were found to significantly shorten the lag phase and decrease the maximum growth rate of S. Typhimurium (p < 0.05). Glucose-lysine MRP (GL MRP) was determined to have the highest relative melanoidin (1.690 ± 0.048 at Ab420) and its efficacy against S. Typhimurium populations was measured at 37 °C and at pH 7.0 and estimated on xylose lysine deoxycholate (XLD) agar. GL MRP significantly reduced S. Typhimurium populations by >1 log CFU/mL at 8 and 24 h after inoculation (p < 0.05). GL MRPs also further decreased S. Typhimurium populations significantly under thermal stress condition (55 °C) compared to optimal (37 °C) by ~1 log CFU/mL (p < 0.05). Overall, GL MRP demonstrated effective antimicrobial activity against S. Typhimurium at 37 °C and 55 °C.

l-Tryptophan synergistically increased carotenoid accumulation with blue light in maize (Zea mays L.) sprouts.

In the present study, l-tryptophan was applied in combination with blue light to modulate carotenoid biosynthesis in maize sprouts. The profiles of carotenoids, chlorophylls, and relative genes in carotenoid biosynthesis and light signaling pathways were studied. l-tryptophan and blue light both promoted the accumulation of carotenoids, and their combination further increased carotenoid content by 120%. l-tryptophan exerted auxin-like effects and stimulated PSY expression in blue light exposure maize sprouts, resulting in increased α- and ß- carotenes. l-tryptophan could also play a photoprotective role through the xanthophyll cycle under blue light. In addition, CRY in the light signaling pathway was critical for carotenoid biosynthesis. These findings provide new insights into the regulation of carotenoid biosynthesis and l-tryptophan could be used in conjunction with blue light to fortify carotenoids in maize sprouts.