Effect of perinatal consumption of low-calorie sweetener on maternal health: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Evidence regarding perinatal low-calorie (or artificial) sweetener (LCS) consumption and its effect on maternal health outcomes is limited and inconclusive. The primary outcomes of our systematic review and meta-analysis were the effect of preconception and pregnancy LCS exposure on reproductive and pregnancy outcomes. Secondary outcomes included long-term maternal health. METHODS: A systematic search of electronic databases, including PubMed, Embase, CINAHL, the Cochrane Library, Scopus, Web of Science, PsycINFO, ProQuest Health and Medical, ClinicalTrials.gov and Google Scholar, was conducted up to 20 November 2023. Primary studies, including clinical trials, cohort studies, case-control studies, which reported any LCS consumption during perinatal period and pregnancy and maternal health outcomes were eligible. A random effects model with restricted maximum likelihood estimation was used for the meta-analysis. We appraised the quality of the included studies using the National Institute of Health study quality appraisal tool and the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation tool. RESULTS: A total of 19 eligible studies with 203,706 participants were included. LCS consumption during pregnancy was associated with 11% increased risk of preterm birth (RR = 1.11, 95% CI: 1.07-1.16, I2 = 0.01%) and 42% increased risk of gestational diabetes (RR = 1.42, 95% CI: 0.98-2.04, I2 = 67.60%) compared with no consumption, however, the effect size for gestational diabetes was not precise as the 95% CI indicated that the effect estimate could range from 2% lower risk to 204% (or 2.04 times) higher risk. We found no association between LCS consumption during pregnancy and gestational weight gain (standardized mean difference (SMD) = 0.04; 95% CI: -0.17 - 0.24, I2 = 41.31%) or gestational age at birth (SMD = 0.00; 95% CI: -0.13 - 0.14, I2 = 80.13%). The effect of LCS consumption on reproductive treatment outcomes were inconsistent. CONCLUSIONS: Based on the evidence available, LCS consumption in pregnancy was associated with increased risk of preterm birth and gestational diabetes. Robust research, such as well-designed randomized trials and large prospective cohort studies, is required to confirm the causal effect of LCS consumption during perinatal period on adverse maternal health outcomes.

Color gamut characteristics of diffractive-light guides of near-eye augmented reality glasses.

We delve into the distinctive color gamut characteristics resulting from color dispersion of surface relief grating (SRG) and wavelength degeneracy of volume holographic optical element (VHOE) in a diffractive light guide. While a laser-like spectrum achieves an impressive 194% sRGB color gamut for both cases, it proves unsuitable for VHOE light guides due to limitations in breaking the field of view (FOV) of the display. Conversely, a broad-band light source, such as LEDs, offers continuous FOV but reduces the common color gamut to 50% sRGB. We then present a newly designed VHOE light guide capable of achieving the common color gamut of 130% sRGB using two multiplexed holograms of each color, closely matching the 133% sRGB achieved by an SRG light guide. This article presents the first theoretical methodology to elucidate color performance of diffractive light guides utilizing VHOEs with holographic multiplexing, affirming their suitability for crafting high-quality near-eye display.

Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.

[Corrigendum] Macrophage­secreted IL­8 induces epithelial­mesen-chymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that a possible error had been identified in the selection of images in Figs. 1 and/or 7. After having consulted their original data, the authors realized that an erroneous image appeared on p. 593, in Fig. 7F [the 'Hep­G2 / IL­8 (5 ng/ml)' data panel], where part of this figure panel was overlapping with an image on p. 589 in Fig. 1C (the 'Hep­G2 Co­cultured' data panel). After a thorough review and verification of the data by all the authors, they have confirmed that the original data presented in the paper were accurate, and the error was solely due to the selection of an incorrect image during figure arrangement. The authors confirm that this mistake in image selection did not affect the overall conclusions reported in the article. A corrected version of Fig. 7, including the correct data for the 'Hep­G2 / IL­8 (5 ng/ml)' panel in Fig. 7F, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for granting them the opportunity to publish this Corrigendum. All the authors agree to the publication of this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 46: 587­596, 2015; DOI: 10.3892/ijo.2014.2761].

Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study.

Purpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA). Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine (group ED, n=76), 0.5-µg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications. Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P <0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P<0.0001). Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.

Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.

Clinical application of CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization in thoracoscopic lung nodule resection: a single-centre retrospective study.

BACKGROUND: Today, the detection rate of lung nodules is increasing. Some of these nodules may become malignant. Thus, timely resection of potentially malignant nodules is essential. However, Identifying the location of nonsurface or soft-textured nodules during surgery is challenging. Various localization techniques have been developed to accurately identify lung nodules. Common methods include preoperative CT-guided percutaneous placement of hook wires and microcoils. Nonetheless, these procedures may cause complications such as pneumothorax and haemothorax. Other methods regarding localization of pulmonary nodules have their own drawbacks. We conducted a clinical study which was retrospective to identify a safe, accurate and suitable method for determining lung nodule localization. To evaluate the clinical value of CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization in thoracoscopic lung nodule resection. METHODS: We retrospectively collected the clinical data of 120 patients who underwent lung nodule localization and resection surgery at the Department of Thoracic Surgery, First Affiliated Hospital of Bengbu Medical College, from January 2020 to January 2022. Among them, 30 patients underwent CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization, 30 patients underwent only CT-assisted body surface localization, 30 patients underwent only intraoperative stereotactic anatomical localization, and 30 patients underwent CT-guided percutaneous microcoil localization. The success rates, complication rates, and localization times of the four lung nodule localization methods were statistically analysed. RESULTS: The success rates of CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization and CT-guided percutaneous microcoil localization were both 96.7%, which were significantly higher than the 70.0% success rate in the CT-assisted body surface localization group (P < 0.05). The complication rate in the combined group was 0%, which was significantly lower than the 60% in the microcoil localization group (P < 0.05). The localization time for the combined group was 17.73 ± 2.52 min, which was significantly less than that (27.27 ± 7.61 min) for the microcoil localization group (P < 0.05). CONCLUSIONS: CT-assisted body surface localization combined with intraoperative stereotactic anatomical localization is a safe, painless, accurate, and reliable method for lung nodule localization.

Usual Choline Intake of Australian Children 6-24 Months: Findings from the Australian Feeding Infants and Toddlers Study (OzFITS 2021).

(1) Background: Despite the important role choline plays in child development, there are no data on dietary choline intake in early childhood in Australia. (2) Aim: In this cross-sectional study, we estimated the usual total choline intake and the proportion exceeding the Adequate Intake (AI) and determined the main dietary sources of choline in infants 6-12 months (n = 286) and toddlers 12-24 months (n = 475) of age. (3) Methods: A single 24-h food record with repeats collected during the 2021 Australian Feeding Infants and Toddlers Study (OzFITS 2021) was used to estimate dietary choline intake. (4) Results: The mean choline intake was 142 ± 1.9 mg/day in infants and 181 ± 1.2 mg/day in toddlers. Only 35% of infants and 23% of toddlers exceeded the AI for choline based on Nutrient Reference Values (NRVs) for Australia and New Zealand. Breastmilk was the leading source of choline, contributing 42% and 14% of total choline intake in infants and toddlers, respectively; however, egg consumers had the highest adjusted choline intakes and probability of exceeding the AI. (5) Conclusions: Findings suggest that choline intake may be suboptimal in Australian infants and toddlers. Further research to examine the impact of low choline intake on child development is warranted.

Association of cord blood vitamin D with child neurodevelopment at 7 years of age.

AIM: The role of fetal vitamin D [25-hydroxyvitamin D (25(OH)D)], one of the nuclear steroid transcription regulators, and brain development is unclear. We previously found a weak but persistent association between cord blood 25(OH)D and child language abilities at 18 months and 4 years of age, but no association with cognition or behaviour. The aim of this study was to investigate the association between cord blood 25(OH)D and a range of neurodevelopmental outcomes in these same children at 7 years of age. METHODS: Cord blood samples from 250 Australian mother-child pairs were analysed for 25(OH)D by mass spectroscopy. Children underwent tests of cognition, language, academic abilities and executive functions with a trained assessor at 7 years of age. Caregivers completed questionnaires to rate their child's behaviour and executive functioning in the home environment. Associations between standardised 25(OH)D and outcomes were assessed using regression models, taking into account possible social and demographic confounders. RESULTS: Standardised 25(OH)D in cord blood was not associated with any test or parent-rated scores. Nor was there any association with the risk of having a poor test or parent-rated score. Likewise, cord blood 25(OH)D categorised as <25, 25-50 and >50 nmol/L was not associated with test scores or parent-rated scores. CONCLUSIONS: There was no evidence that cord blood vitamin D concentration or deficiency was associated with cognition, language, academic abilities, executive functioning or behaviour at 7 years of age.

Urinary Ferritin as a Noninvasive Means of Assessing Iron Status in Young Children.

BACKGROUND: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin concentration is the preferred biomarker for measuring iron status because it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A noninvasive means to measure iron status would be attractive to either diagnose or screen for ID in young children. OBJECTIVES: This study aimed to determine the correlation between urinary and serum ferritin concentrations in young children; to determine whether correcting urinary ferritin for creatinine and specific gravity improves the correlation; and to determine a urine ferritin cut point to predict ID. METHODS: Validation study was conducted using paired serum and urine collected from 3-y-old children (n = 142) participating in a longitudinal birth cohort study: the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive values of urinary ferritin amount in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin concentration of <12 ng/mL). RESULTS: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin [r = 0.53 (0.40-0.64)] and performed well in predicting those with ID (area under the curve: 0.85; 95% confidence interval: 0.75, 0.94). Urine ferritin <2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) owing to the low prevalence of ID in the sample (16%). CONCLUSIONS: Urine ferritin shows good diagnostic performance for ID. This noninvasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations.

Differentiating mixed epithelial and stromal tumor family from predominantly cystic renal cell carcinoma using magnetic resonance imaging-based Bosniak classification system version 2019.

PURPOSE: To differentiate mixed epithelial and stromal tumor family (MESTF) of the kidney from predominantly cystic renal cell carcinoma (RCC) using the magnetic resonance imaging (MRI)-based Bosniak classification system version 2019 (v2019). MATERIALS AND METHODS: The study included 36 consecutive patients with MESTF and 77 with predominantly cystic RCC who underwent preoperative renal MRI. One radiologist evaluated and documented the clinical and MRI characteristics (age, sex, laterality, R.E.N.A.L. Nephrometry Score [RNS], surgical approach, the signal intensity on T2-weighted imaging, restricted diffusion and enhancement features in corticomedullary phase). Blinded to clinical and pathological information, another two radiologists independently evaluated Bosniak category of all masses. Interobserver agreement based on Bosniak classification system v2019 was measured by the weighted Cohen/Conger's Kappa coefficient. Furthermore, predominantly cystic RCCs and MESTFs were divided into low (categories I, II, and IIF) and high-class (categories III, and IV) tumors. The independent sample t test (Mann-Whitney U test) or Pearson Chi-square test (Fisher's exact probability test) was utilized to compare clinical and imaging characteristics between MESTFs and predominantly cystic RCCs. The performance of the Bosniak classification system v2019 in distinguishing MESTF from predominantly cystic RCC was investigated via receiver operating characteristic curve analysis. RESULTS: MESTF and predominantly cystic RCC groups significantly differed in terms of age, lesion size, RNS, restricted diffusion, and obvious enhancement in corticomedullary phase, but not sex, laterality, surgical approach, and the signal intensity on T2WI. Interobserver agreement was substantially based on the Bosniak classification system v2019. There were 24 low-class tumors and 12 high-class tumors in the MESTF group. Meanwhile, 13 low-class tumors and 64 high-class tumors were observed in the predominantly cystic RCC group. The distribution of low- or high-class tumors significantly differed between the MESTF and predominantly cystic RCC groups. Bosniak classification system v2019 had excellent discrimination (cutoff value = category III), and an area under curve value was 0.81; accuracy, 80.5%; sensitivity, 87.0%; and specificity, 66.7%. CONCLUSION: The MRI-based Bosniak classification system v2019 can effectively distinguish MESTF from predominantly cystic RCC if category III was used as a cutoff reference.

Predictive potential of preoperative Naples prognostic score-based nomogram model for the prognosis in surgical resected thoracic esophageal squamous cell carcinoma patients: A retrospective cohort study.

The present study aimed to establish an effective prognostic nomogram model based on the Naples prognostic score (NPS) for resectable thoracic esophageal squamous cell carcinoma (ESCC). A total of 277 patients with ESCC, who underwent standard curative esophagectomy and designated as study cohort, were retrospectively analyzed. The patients were divided into different groups, including NPS 0, NPS 1, NPS 2, and NPS 3 or 4 groups, for further analysis, and the results were validated in an external cohort of 122 ESCC patients, who underwent surgery at another cancer center. In our multivariate analysis of the study cohort showed that the tumor-node-metastasis (TNM) stage, systemic inflammation score, and NPS were the independent prognostic factors for the overall survival (OS) and progression-free survival (PFS) durations. In addition, the differential grade was also an independent prognostic factor for the OS in the patients with ESCC after surgery (all P < .05). The area under the curve of receiver operator characteristics for the PFS and OS prediction with systemic inflammation score and NPS were 0.735 (95% confidence interval [CI] 0.676-0.795, P < .001) and 0.835 (95% CI 0.786-0.884, P < .001), and 0.734 (95% CI 0.675-0.793, P < .001) and 0.851 (95% CI 0.805-0.896, P < .001), respectively. The above independent predictors for OS or PFS were all selected in the nomogram model. The concordance indices (C-indices) of the nomogram models for predicting OS and PFS were 0.718 (95% CI 0.681-0.755) and 0.669 (95% CI 0.633-0.705), respectively, which were higher than that of the 7th edition of American Joint Committee on Cancer TNM staging system [C-index 0.598 (95% CI 0.558-0.638) for OS and 0.586 (95% CI 0.546-0.626) for PFS]. The calibration curves for predicting the 5-year OS or PFS showed a good agreement between the prediction by nomogram and actual observation. In the external validation cohort, the nomogram discrimination for OS was better than that of the 7th edition of TNM staging systems [C-index: 0.697 (95% CI 0.639-0.755) vs 0.644 (95% CI 0.589-0.699)]. The calibration curves showed good consistency in predicting the 5-year survival between the actual observation and nomogram predictions. The decision curve also showed a higher potential of the clinical application of predicting the 5-years OS of the proposed nomogram model as compared to that of the 7th edition of TNM staging systems. The preoperative NPS-based nomogram model had a certain potential role for predicting the prognosis of ESCC patients.

Plasma Sphingomyelins and Carnitine Esters of Infants Consuming Whole Goat or Cow Milk-Based Infant Formulas or Human Milk.

BACKGROUND: Infant formulas are typically manufactured using skimmed milk, whey proteins, and vegetable oils, which excludes milk fat globule membranes (MFGM). MFGM contains polar lipids, including sphingomyelin (SM). OBJECTIVE: The objective of this study was comparison of infant plasma SM and acylcarnitine species between infants who are breastfed or receiving infant formulas with different fat sources. METHODS: In this explorative study, we focused on SM and acylcarnitine species concentrations measured in plasma samples from the TIGGA study (ACTRN12608000047392), where infants were randomly assigned to receive either a cow milk-based infant formula (CIF) with vegetable oils only or a goat milk-based infant formula (GIF) with a goat milk fat (including MFGM) and vegetable oil mixture to the age ≥4 mo. Breastfed infants were followed as a reference group. Using tandem mass spectrometry, SM species in the study formulas and SM and acylcarnitine species in plasma samples collected at the age of 4 mo were analyzed. RESULTS: Total SM concentrations (∼42 µmol/L) and patterns of SM species were similar in both formulas. The total plasma SM concentrations were not different between the formula groups but were 15 % (CIF) and 21% (GIF) lower in the formula groups than in the breastfed group. Between the formula groups, differences in SM species were statistically significant but small. Total carnitine and major (acyl) carnitine species were not different between the groups. CONCLUSIONS: The higher total SM concentration in breastfed than in formula-fed infants might be related to a higher SM content in human milk, differences in cholesterol metabolism, dietary fatty acid intake, or other factors not yet identified. SM and acylcarnitine species composition in plasma is not closely related to the formula fatty acid composition. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12608000047392.

Effective interventions in preventing gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Lifestyle choices, metformin, and dietary supplements may prevent GDM, but the effect of intervention characteristics has not been identified. This review evaluated intervention characteristics to inform the implementation of GDM prevention interventions. METHODS: Ovid, MEDLINE/PubMed, and EMBASE databases were searched. The Template for Intervention Description and Replication (TIDieR) framework was used to examine intervention characteristics (who, what, when, where, and how). Subgroup analysis was performed by intervention characteristics. RESULTS: 116 studies involving 40,940 participants are included. Group-based physical activity interventions (RR 0.66; 95% CI 0.46, 0.95) reduce the incidence of GDM compared with individual or mixed (individual and group) delivery format (subgroup p-value = 0.04). Physical activity interventions delivered at healthcare facilities reduce the risk of GDM (RR 0.59; 95% CI 0.49, 0.72) compared with home-based interventions (subgroup p-value = 0.03). No other intervention characteristics impact the effectiveness of all other interventions. CONCLUSIONS: Dietary, physical activity, diet plus physical activity, metformin, and myoinositol interventions reduce the incidence of GDM compared with control interventions. Group and healthcare facility-based physical activity interventions show better effectiveness in preventing GDM than individual and community-based interventions. Other intervention characteristics (e.g. utilization of e-health) don't impact the effectiveness of lifestyle interventions, and thus, interventions may require consideration of the local context.

The effect of any given intervention to prevent gestational diabetes (high blood sugar levels that arise during pregnancy) may depend on the way it is delivered (how, when, what, etc). This study reviewed published literature to investigate if the effects of interventions (diet, exercise, metformin, probiotics, myoinositol) to prevent gestational diabetes differ according to the way it is being delivered (e.g., online vs in-person, by health professionals or others, etc.). Exercise delivered to group settings, or those delivered at a healthcare facility worked better to prevent gestational diabetes. Although we did not observe any differences with other delivery characteristics (e.g., online vs in-person), it does not mean they are always equally effective, it is important to consider individual situations when prescribing or developing interventions.

Genome-wide identification of JAZ gene family in sugarcane and function analysis of ScJAZ1/2 in drought stress response and flowering regulation.

The JASMONATE ZIM DOMAIN (JAZ) proteins are a key inhibitors of the jasmonic acid (JA) signaling pathway that play an important role in the regulation of plant growth and development and environmental stress responses. However, there is no systematic identification and functional analysis of JAZ gene family members in sugarcane. In this study, a total of 49 SsJAZ genes were identified from the wild sugarcane species Saccharum spontaneum genome that were unevenly distributed on 13 chromosomes. Phylogenetic analysis showed that all SsJAZ members can be divided into six groups, and most of the SsJAZ genes contained photoreactive and ABA-responsive elements. RNA-seq analysis revealed that SsJAZ1-1/2/3/4 and SsJAZ7-1 were significantly upregulated under drought stress. The transcript level of ScJAZ1 which is the homologous gene of SsJAZ1 in modern sugarcane cultivars was upregulated by JA, PEG, and abscisic acid (ABA). Moreover, ScJAZ1 can interact with three other JAZ proteins to form heterodimers. The spatial and temporal expression analysis showed that SsJAZ2-1/2/3/4 were highly expressed in different tissues and growth stages and during the day-night rhythm between 10:00 and 18:00. Overexpression of ScJAZ2 in Arabidopsis accelerated flowering through activating the expression of AtSOC1, AtFT, and AtLFY. Moreover, the transcription level of ScJAZ2 was about 30-fold in the early-flowering sugarcane variety than that of the non-flowering variety, indicating ScJAZ2 positively regulated flowering. This first systematic analysis of the JAZ gene family and function analysis of ScJAZ1/2 in sugarcane provide key candidate genes and lay the foundation for sugarcane breeding.

Revealing Novel Genes Related to Parkinson's Disease Pathogenesis and Establishing an associated Model.

Parkinson's disease (PD) represents a multifaceted neurological disorder whose genetic underpinnings warrant comprehensive investigation. This study focuses on identifying genes integral to PD pathogenesis and evaluating their diagnostic potential. Initially, we screened for differentially expressed genes (DEGs) between PD and control brain tissues within a dataset comprising larger number of specimens. Subsequently, these DEGs were subjected to weighted gene co-expression network analysis (WGCNA) to discern relevant gene modules. Notably, the yellow module exhibited a significant correlation with PD pathogenesis. Hence, we conducted a detailed examination of the yellow module genes using a cytoscope-based approach to construct a protein-protein interaction (PPI) network, which facilitated the identification of central hub genes implicated in PD pathogenesis. Employing two machine learning techniques, including XGBoost and LASSO algorithms, along with logistic regression analysis, we refined our search to three pertinent hub genes: FOXO3, HIST2H2BE, and HDAC1, all of which demonstrated a substantial association with PD pathogenesis. To corroborate our findings, we analyzed two PD blood datasets and clinical plasma samples, confirming the elevated expression levels of these genes in PD patients. The association of the genes with PD, as reflected by the area under the curve (AUC) values for FOXO3, HIST2H2BE, and HDAC1, were moderate for each gene. Collectively, this research substantiates the heightened expression of FOXO3, HIST2H2BE, and HDAC1 in both PD brain and blood samples, underscoring their pivotal contribution to the pathogenesis of PD.

Characterization of tumor microbiome and associations with prognosis in intrahepatic cholangiocarcinoma.

BACKGROUND: The tumor microbiome has been characterized in several malignancies; however, no previous studies have investigated its role in intrahepatic cholangiocarcinoma (ICC). Hence, we explored the tumor microbiome and its association with prognosis in ICC. METHODS: One hundred and twenty-one ICC tumor samples and 89 adjacent normal tissues were profiled by 16S rRNA sequencing. Microbial differences between tumor and adjacent nontumoral liver tissues were assessed. Tumor microbial composition was then evaluated to detect its association with prognosis. Finally, a risk score calculated by the tumor microbiota was accessed by the least absolute shrinkage and selector operator method (Lasso) to predict prognosis of ICC. RESULTS: The tumor microbiome displayed a greater diversity than that in adjacent nontumoral liver tissues. Tumor samples were characterized by a higher abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteriota. Higher tumor microbial α diversity was associated with lymph node metastasis and predicted shortened overall survival (OS) and recurrence-free survival (RFS). A total of 11 bacteria were selected to generate the risk score by Lasso. This score showed potential in predicting OS, and was an independent risk factor for OS. CONCLUSION: In conclusion, our study characterized the tumor microbiome and revealed its role in predicting prognosis in ICC.

Icariin ameliorates glycolytic dysfunction in Alzheimer's disease models by activating the Wnt/ß-catenin signaling pathway.

It was reported that the Wnt/ß-catenin pathway is involved in the regulation of aerobic glycolysis and that brain glycolytic dysfunction results in the development of Alzheimer's disease (AD). Icariin (ICA), an active component extracted from Epimedii Folium, has been reported to produce neuroprotective effects in multiple models of AD, but its underlying mechanism remains to be fully described. We aimed to investigate the protective effects of ICA on animal and cell models of AD and confirm whether the Wnt/ß-catenin pathway has functions in the neuroprotective function of ICA. The 3 × Tg-AD mice were treated with ICA. HT22 cells, the Aß25-35 peptide and Dickkopf-1 (DKK1) agent (a specific inhibitor of the Wnt/ß-catenin pathway) were used to further explore the underlying mechanism of ICA that produces anti-AD effects. Behavioral examination, western blotting assay, staining analysis, biochemical test, and lactate dehydrogenase (LDH) assays were applied. We first demonstrated that ICA significantly improved cognitive function and autonomous behavior, reduced neuronal damage, and reversed the protein levels and activities of glycolytic key enzymes, and expression of protein molecules of the canonical Wnt signaling pathway, in 3 × Tg-AD mice back to wild-type levels. Next, we further found that ICA increased cell viability and effectively improved the dysfunctional glycolysis in HT22 cells injured by Aß25-35. However, when canonical Wnt signaling was inhibited by DKK1, the above effects of ICA on glycolysis were abolished. In summary, ICA exerts neuroprotective effects in 3 × Tg-AD animals and AD cellular models by enhancing the function of glycolysis through activation of the Wnt/ß-catenin pathway.

ADORA3: A Key Player in the Pathogenesis of Intracranial Aneurysms and a Potential Diagnostic Biomarker.

BACKGROUND: The effects of genes on the development of intracranial aneurysms (IAs) remain to be elucidated, and reliable blood biomarkers for diagnosing IAs are yet to be established. This study aimed to identify genes associated with IAs pathogenesis and explore their diagnostic value by analyzing IAs datasets, conducting vascular smooth muscle cells (VSMC) experiments, and performing blood detection. METHODS: IAs datasets were collected and the differentially expressed genes were analyzed. The selected genes were validated in external datasets. Autophagy was induced in VSMC and the effect of selected genes was determined. The diagnostic value of selected gene on the IAs were explored using area under curve (AUC) analysis using IAs plasma samples. RESULTS: Analysis of 61 samples (32 controls and 29 IAs tissues) revealed a significant increase in expression of ADORA3 compared with normal tissues using empirical Bayes methods of "limma" package; this was further validated by two external datasets. Additionally, induction of autophagy in VSMC lead to upregulation of ADORA3. Conversely, silencing ADORA3 suppressed VSMC proliferation and autophagy. Furthermore, analysis of an IAs blood sample dataset and clinical plasma samples demonstrated increased ADORA3 expression in patients with IA compared with normal subjects. The diagnostic value of blood ADORA3 expression in IAs was moderate when analyzing clinical samples (AUC: 0.756). Combining ADORA3 with IL2RB or CCR7 further enhanced the diagnostic ability for IAs, with the AUC value over 0.83. CONCLUSIONS: High expression of ADORA3 is associated with IAs pathogenesis, likely through its promotion of VSMC autophagy. Furthermore, blood ADORA3 levels have the potential to serve as an auxiliary diagnostic biomarker for IAs.

Pericoronary adipose tissue attenuation in patients with acute aortic dissection based on coronary computed tomography angiography.

Background: Periaortic fat is associated with coronary disease. Thus, it was hypothesized that the inflammation associated with acute aortic dissection (AAD) spreads to pericoronary adipose tissue (PCAT) via thoracic periaortic fat. Pericoronary adipose tissue attenuation (PCATa) serves as a marker for inflammation of perivascular adipose tissue (PVAT). This study sought to examine PCATa in individuals diagnosed with AAD. Methods: Consecutive patients with chest pain from May 2020 to September 2022 were prospectively enrolled in this study and underwent coronary computed tomography angiography (CCTA) and/or aorta computed tomography angiography (CTA). Based on the results of the CTA, the patients were divided into the following two groups: (I) the AAD group; and (II) the non-AAD group. PCATa of the right coronary angiography (RCA), left anterior descending (LAD), and left circumflex (LCx) was quantified for each patient using semi-automated software. The PCATa values were compared between the AAD and non-AAD patients according to the atherosclerosis of the coronary arteries. Similarly, the PCATa values of the AAD patients were compared between the preoperative and postoperative steady states. Results: A total of 136 patients (42 female, 94 male; mean age: 63.3±11.9 years) were divided into the two groups according to the presence of aortic dissection on CTA. The RCAPCATa, LADPCATa, and LCxPCATa values were significantly higher in the AAD subjects than the non-AAD subjects, regardless of the presence or absence of atherosclerosis in the coronary arteries [-85.1±9.3 vs. -92.9±10.0 Hounsfield unit (HU); -83.2±7.4 vs. -89.9±9.1 HU; -77.5±8.4 vs. -85.6±7.9 HU, all P<0.001). The preoperative RCAPCATa, LADPCATa, and LCxPCATa values were higher in the AAD patients than the postoperative steady-state patients (-82.9±8.7 vs. -97.6±8.8 HU; -79.8±7.6 vs. -92.8±6.8 HU; -74.6±7.1 vs. -87.7±6.9 HU, all P<0.001). According to the multivariable logistic regression analysis, high RCAPCATa and LADPCATa values were associated with AAD regardless of the degree of stenosis [odds ratio (OR) =0.014; 95% confidence interval (CI): 0.001-0.177; P=0.001 and OR =0.010; 95% CI: 0.001-0.189; P=0.002]. Conclusions: PCATa on computed tomography was increased in patients with AAD regardless of the presence or absence of coronary artery disease (CAD). This suggests that vascular inflammation is present in AAD independent of CAD. Further research should be conducted to investigate the potential of this imaging biomarker to predict AAD and monitor patients' responses to therapies for AAD.

Genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus.

X chromosome inactivation can balance the effects of the two X chromosomes in females, and emerging evidence indicates that numerous genes on the inactivated X chromosome have the potential to evade inactivation. The mechanisms of escape include modification of DNA, RNA, histone, epitope, and various regulatory proteins, as well as the spatial structure of chromatin. The study of X chromosome inactivation escape has paved the way for investigating sex dimorphism in human diseases, particularly autoimmune diseases. It has been demonstrated that the presence of TLR7, CD40L, IRAK-1, CXCR3, and CXorf21 significantly contributes to the prevalence of SLE (systemic lupus erythematosus) in females. This article mainly reviews the molecular mechanisms underlying these genes that escape from X-chromosome inactivation and sexual dimorphism of systemic lupus erythematosus. Therefore, elucidating the molecular mechanisms underlying sexual dimorphism in SLE is not only crucial for diagnosing and treating the disease, but also holds theoretical significance in comprehensively understanding the development and regulatory mechanisms of the human immune system.