Biofluorescence imaging-guided spatial metabolic tracing: In vivo tracking of metabolic activity in circulating tumor cell-mediated multi-organ metastases.

Circulating tumor cells (CTC) are considered metastatic precursors that are shed from the primary or metastatic deposits and navigate the bloodstream before undergoing extravasation to establish distant metastases. Metabolic reprogramming appears to be a hallmark of metastatic progression, yet current methods for evaluating metabolic heterogeneity within organ-specific metastases in vivo are limited. To overcome this challenge, we present Biofluorescence Imaging-Guided Spatial Metabolic Tracing (BIGSMT), a novel approach integrating in vivo biofluorescence imaging, stable isotope tracing, stain-free laser capture microdissection, and liquid chromatography-mass spectrometry. This innovative technology obviates the need for staining or intricate sample preparation, mitigating metabolite loss, and substantially enhances detection sensitivity and accuracy through chemical derivatization of polar metabolites in central carbon pathways. Application of BIGSMT to a preclinical CTC-mediated metastasis mouse model revealed significant heterogeneity in the in vivo carbon flux from glucose into glycolysis and the tricarboxylic acid (TCA) cycle across distinct metastatic sites. Our analysis indicates that carbon predominantly enters the TCA cycle through the enzymatic reaction catalyzed by pyruvate dehydrogenase. Thus, our spatially resolved BIGSMT technology provides fresh insights into the metabolic heterogeneity and evolution during melanoma CTC-mediated metastatic progression and points to novel therapeutic opportunities.

Humoral immunity and safety of respiratory virus vaccines in systemic lupus erythematosus population: a meta-analysis based on twenty-five observational studies.

BACKGROUND: Systemic lupus erythematosus (SLE), an extensive autoimmune disorder, compromises viral resistance and alters immune responses post respiratory virus vaccines. This study aims to assess immune response levels and safety in SLE patients following respiratory virus vaccines. METHODS: Extensive searches, until 1 March 2024, were conducted using PubMed, EMBASE, and Cochrane Library. Outcomes, encompassing seroconversion rate (SCR), antibody and IgG titers, neutralizing antibodies, anti-spike antibodies, anti-receptor binding domain (RBD) IgG, and adverse events, were appraised. RESULTS: Sixteen articles, comprising 25 observational studies, were included. SLE patients exhibited lower SCR (OR = 0.42, 95%CI: 0.26 to 0.69), antibody titers (SMD=-2.84, 95%CI: -3.36 to -1.61), and neutralizing antibodies (OR = 0.27, 95%CI: 0.13 to 0.56) compared to the healthy population post respiratory virus vaccines. Notably, differences were statistically insignificant for anti-RBD IgG (OR = 1.75, 95%CI: 0.10 to 29.42), IgG titers (SMD=-2.54, 95%CI: -5.57 to -0.49), anti-spike antibodies (OR = 0.35, 95%CI: 0.08 to 1.53), injection site discomfort (OR = 1.03, 95%CI: 0.52 to 2.06), fatigue (OR = 1.23, 95%CI: 0.74 to 2.03), fever (OR = 1.02, 95%CI: 0.64 to 1.63), localized reactions (OR = 0.69, 95%CI: 0.37 to 1.30), systemic reactions (OR = 1.00, 95%CI: 0.59 to 1.69), allergic reactions (OR = 5.11, 95%CI: 0.24 to 107.10), self-reported vaccination-related adverse events (OR = 1.61, 95%CI: 0.56 to 4.63), and disease flares after vaccination (OR = 1.00, 95%CI: 0.14 to 7.28). CONCLUSION: Despite the reduced immune response and host protection in SLE patients post-Corona Virus Disease 2019 (COVID-19) and influenza vaccines compared to the healthy population, safety profiles are comparable. Therefore, it is recommended that SLE patients receive COVID-19 and influenza viral vaccines to fortify their resistance.

Ene-Reductase-Catalyzed Aromatization of Simple Cyclohexanones to Phenols.

Direct aromatization of cyclohexanones to synthesize substituted phenols represents a significant challenge in modern synthetic chemistry. Herein, we describe a novel ene-reductase (TsER) catalytic system that converts substituted cyclohexanones into the corresponding phenols. This process involves the successive dehydrogenation of two saturated carbon-carbon bonds within the six-membered ring of cyclohexanones and utilizes molecular oxygen to drive the reaction cycle. It demonstrates a versatile and efficient approach for the synthesis of substituted phenols, providing a valuable complement to existing chemical methodologies.

Nonparametric second-order estimation for spatiotemporal point patterns.

Many existing methodologies for analyzing spatiotemporal point patterns are developed based on the assumption of stationarity in both space and time for the second-order intensity or pair correlation. In practice, however, such an assumption often lacks validity or proves to be unrealistic. In this paper, we propose a novel and flexible nonparametric approach for estimating the second-order characteristics of spatiotemporal point processes, accommodating non-stationary temporal correlations. Our proposed method employs kernel smoothing and effectively accounts for spatial and temporal correlations differently. Under a spatially increasing-domain asymptotic framework, we establish consistency of the proposed estimators, which can be constructed using different first-order intensity estimators to enhance practicality. Simulation results reveal that our method, in comparison with existing approaches, significantly improves statistical efficiency. An application to a COVID-19 dataset further illustrates the flexibility and interpretability of our procedure.

Psychotherapeutic and pharmacological agents for post-traumatic stress disorder with sleep disorder: network meta-analysis.

OBJECTIVE: The current guidelines and canonical norms of diagnosis or treatment for Post-traumatic stress disorder (PTSD) with sleep disorder are still conflicting and have not yet reached a consensus. This study aimed to unravel the most effective countermeasures between two categories (psychotherapy and pharmacotherapy) put forward by the National Institute for Health and Clinical Excellence (NICE) and World Federation of Societies of Biological Psychiatry (WFSBP) respectively to treat PTSD individuals co-exist with sleep disorders. METHODS: Four databases, including PubMed, EMBASE, Cochrane Library, and APA PsyNet, were searched from inception to February 02, 2023. RESULTS: Twenty articles with 24 Randomized controlled trials (RCTs) and a total number of 1,647 participants were included. As demonstrated in the network meta-analysis comparison results, CBT-I (standardized mean differences (SMD) = -1.51,95% confidence interval (CI):-2.55 to -0.47), CBT-I plus IRT (SMD = -1.71, 95%CI:-3.39, -0.03), prazosin (SMD = -0.87,95%CI:-1.59 to -0.16) and hydroxyzine (SMD = -1.06, 95%CI: -1.94 to -0.19) significantly reduced PTSD symptoms compared with placebo. In contrast to placebo, CBT-I (SMD = -5.61,95%CI:-8.82 to -2.40) significantly improved sleep quality. For nightmare severity, IRT (SMD =-0.65, 95%CI:-1.00 to -0.31), prazosin (SMD = -1.20,95%CI:-1.72 to -0.67) and hydroxyzine (SMD = -0.98,95%CI:-1.58 to -0.37) significantly reduced nightmare severity in comparison with placebo. CONCLUSIONS: This study suggested that under most circumstances, psychotherapy namely CBT-I had a favorable profile, but pharmacotherapy with prazosin was effective in managing nightmare severity. The sole avail of CBT-I was recommended to improving sleep quality while CBT-I and CBT-I plus IRT showed excellent management of PTSD symptom severity. Exposure to CBT-I isrecommended for depression. The relevant clinical guidelines for the management of individuals with PTSD and sleep disorders may regard this as a reference. PROSPERO: CRD42023415240.

The carrier function and inhibition effect on benign prostatic hyperplasia of a glucan from Epimedium brevicornu Maxim.

Epimedium, a traditional Chinese medicine commonly used as a dietary supplement, contains polysaccharides and flavonoids as its main bioactive ingredients. In this study, a neutral homogeneous polysaccharide (EPSN-1) was isolated from Epimedium brevicornu Maxim. EPSN-1 was identified as a glucan with a backbone of →4)-α-D-Glcp-(1→, branched units comprised α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Glcp-(1→6)-ß-D-Glcp-(1→ and α-D-Glcp-(1→ connected to the C6 position of backbone. The conformation of EPSN-1 in aqueous solution indicated its potential to form nanoparticles. This paper aims to investigate the carrier and pharmacodynamic activity of EPSN-1. The findings demonstrated that, on the one hand, EPSN-1, as a functional ingredient, may load Icariin (ICA) through non-covalent interactions, improving its biopharmaceutical properties such as solubility and stability, thereby improving its intestinal absorption. Additionally, as an effective ingredient, EPSN-1 could help maintain the balance of the intestinal environment by increasing the abundance of Parabacteroides, Lachnospiraceae UGG-001, Anaeroplasma, and Eubacterium xylanophilum group, while decreasing the abundance of Allobaculum, Blautia, and Adlercreutzia. Overall, this dual action of EPSN-1 sheds light on the potential applications of natural polysaccharides, highlighting their dual role as carriers and contributors to biological activity.

Lower class competence stereotypes of the upper class increase class conflict: mediation by intergroup envy and moderation by upward social mobility belief.

Background: With increasing gaps between the rich and poor, potential risk factors for class conflict have attracted increasing attention from researchers. Although cognitive factors are known to be significant predictors of class-conflict behavior, limited attention has been paid to competence stereotypes of the upper class. When considering economic inequality, people pay more attention to competence stereotypes of the upper class, which may have adverse effects. This study aimed to investigate the relationship between competence stereotypes held by the lower class about the upper class and class conflict, and to test the mediating role of intergroup envy in this relationship and the moderating role of upward social mobility belief. Methods: Data were collected from a convenience sample from a comprehensive university in China. Based on scores on subjective and objective class scales, 284 lower-class college students (103 males and 181 females) aged 18-24 were selected to participate (both their subjective and objective scores were lower than 3 points). Their endorsement of upper-class competence stereotypes, intergroup envy, upward social mobility beliefs, and class conflict were measured using a well-validated self-report questionnaire. Results: The main data were analyzed using correlation analysis, the SPSS macro PROCESS (Model 7), and simple slope analysis. The results show a significant positive correlation between competence stereotypes held by lower-class college students toward the higher class and class conflict, and this connection was mediated by intergroup envy. Moreover, the indirect effect of intergroup envy on this link was moderated by upward social mobility beliefs; this effect was stronger for college students with lower upward social mobility beliefs. Conclusion: This study broadens our understanding of how and when competence stereotypes among the lower class concerning the upper class are related to class conflict. Researchers and policymakers should pay special attention to competence stereotypes of the upper class, especially intergroup envy and class conflict among lower-class individuals with lower levels of upward social mobility beliefs.

Defective interferon signaling in the circulating monocytes of type 2 diabetic mice.

Type 2 diabetes mellitus (T2DM) is associated with poor outcome after stroke. Peripheral monocytes play a critical role in the secondary injury and recovery of damaged brain tissue after stroke, but the underlying mechanisms are largely unclear. To investigate transcriptome changes and molecular networks across monocyte subsets in response to T2DM and stroke, we performed single-cell RNA-sequencing (scRNAseq) from peripheral blood mononuclear cells and bulk RNA-sequencing from blood monocytes from four groups of adult mice, consisting of T2DM model db/db and normoglycemic control db/+ mice with or without ischemic stroke. Via scRNAseq we found that T2DM expands the monocyte population at the expense of lymphocytes, which was validated by flow cytometry. Among the monocytes, T2DM also disproportionally increased the inflammatory subsets with Ly6C+ and negative MHC class II expression (MO.6C+II-). Conversely, monocytes from control mice without stroke are enriched with steady-state classical monocyte subset of MO.6C+II+ but with the least percentage of MO.6C+II- subtype. Apart from enhancing inflammation and coagulation, enrichment analysis from both scRNAseq and bulk RNAseq revealed that T2DM specifically suppressed type-1 and type-2 interferon signaling pathways crucial for antigen presentation and the induction of ischemia tolerance. Preconditioning by lipopolysaccharide conferred neuroprotection against ischemic brain injury in db/+ but not in db/db mice and coincided with a lesser induction of brain Interferon-regulatory-factor-3 in the brains of the latter mice. Our results suggest that the increased diversity and altered transcriptome in the monocytes of T2DM mice underlie the worse stroke outcome by exacerbating secondary injury and potentiating stroke-induced immunosuppression. Significance Statement: The mechanisms involved in the detrimental diabetic effect on stroke are largely unclear. We show here, for the first time, that peripheral monocytes have disproportionally altered the subsets and changed transcriptome under diabetes and/or stroke conditions. Moreover, genes in the IFN-related signaling pathways are suppressed in the diabetic monocytes, which underscores the immunosuppression and impaired ischemic tolerance under the T2DM condition. Our data raise a possibility that malfunctioned monocytes may systemically and focally affect the host, leading to the poor outcome of diabetes in the setting of stroke. The results yield important clues to molecular mechanisms involved in the detrimental diabetic effect on stroke outcome.

Time-Series MR Images Identifying Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Using a Deep Learning Approach.

BACKGROUND: Pathological complete response (pCR) is an essential criterion for adjusting follow-up treatment plans for patients with breast cancer (BC). The value of the visual geometry group and long short-term memory (VGG-LSTM) network using time-series dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for pCR identification in BC is unclear. PURPOSE: To identify pCR to neoadjuvant chemotherapy (NAC) using deep learning (DL) models based on the VGG-LSTM network. STUDY TYPE: Retrospective. POPULATION: Center A: 235 patients (47.7 ± 10.0 years) were divided 7:3 into training (n = 164) and validation set (n = 71). Center B: 150 patients (48.5 ± 10.4 years) were used as test set. FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted spin-echo sequence imaging, and gradient echo DCE sequence imaging. ASSESSMENT: Patients underwent MRI examinations at three sequential time points: pretreatment, after three cycles of treatment, and prior to surgery, with tumor regions of interest manually delineated. Histopathology was the gold standard. We used VGG-LSTM network to establish seven DL models using time-series DCE-MR images: pre-NAC images (t0 model), early NAC images (t1 model), post-NAC images (t2 model), pre-NAC and early NAC images (t0 + t1 model), pre-NAC and post-NAC images (t0 + t2 model), pre-NAC, early NAC and post-NAC images (t0 + t1 + t2 model), and the optimal model combined with the clinical features and imaging features (combined model). The models were trained and optimized on the training and validation set, and tested on the test set. STATISTICAL TESTS: The DeLong, Student's t-test, Mann-Whitney U, Chi-squared, Fisher's exact, Hosmer-Lemeshow tests, decision curve analysis, and receiver operating characteristics analysis were performed. P < 0.05 was considered significant. RESULTS: Compared with the other six models, the combined model achieved the best performance in the test set yielding an AUC of 0.927. DATA CONCLUSION: The combined model that used time-series DCE-MR images, clinical features and imaging features shows promise for identifying pCR in BC. TECHNICAL EFFICACY: Stage 4.

Direct Synthesis of α-Ketoamides via Copper-Catalyzed Reductive Amidation of Nitroarenes with α-Oxocarboxylic Acids.

Nitroarenes are known for their stability, low toxicity, easy availability, and cost-effectiveness, making them one of the most fundamental chemical feedstocks. The direct utilization of nitroarenes as nitrogen sources in amidation reactions offers significant advantages over using arylamines. Herein, we disclose a streamlined method for constructing α-ketoamides through the direct coupling of nitroarenes with α-oxocarboxylic acids. This transformation obviates the need for preparing, isolating, and purifying arylamines, leading to improved efficiency, cost-effectiveness, and time savings.

PresRecST: a novel herbal prescription recommendation algorithm for real-world patients with integration of syndrome differentiation and treatment planning.

OBJECTIVES: Herbal prescription recommendation (HPR) is a hot topic and challenging issue in field of clinical decision support of traditional Chinese medicine (TCM). However, almost all previous HPR methods have not adhered to the clinical principles of syndrome differentiation and treatment planning of TCM, which has resulted in suboptimal performance and difficulties in application to real-world clinical scenarios. MATERIALS AND METHODS: We emphasize the synergy among diagnosis and treatment procedure in real-world TCM clinical settings to propose the PresRecST model, which effectively combines the key components of symptom collection, syndrome differentiation, treatment method determination, and herb recommendation. This model integrates a self-curated TCM knowledge graph to learn the high-quality representations of TCM biomedical entities and performs 3 stages of clinical predictions to meet the principle of systematic sequential procedure of TCM decision making. RESULTS: To address the limitations of previous datasets, we constructed the TCM-Lung dataset, which is suitable for the simultaneous training of the syndrome differentiation, treatment method determination, and herb recommendation. Overall experimental results on 2 datasets demonstrate that the proposed PresRecST outperforms the state-of-the-art algorithm by significant improvements (eg, improvements of P@5 by 4.70%, P@10 by 5.37%, P@20 by 3.08% compared with the best baseline). DISCUSSION: The workflow of PresRecST effectively integrates the embedding vectors of the knowledge graph for progressive recommendation tasks, and it closely aligns with the actual diagnostic and treatment procedures followed by TCM doctors. A series of ablation experiments and case study show the availability and interpretability of PresRecST, indicating the proposed PresRecST can be beneficial for assisting the diagnosis and treatment in real-world TCM clinical settings. CONCLUSION: Our technology can be applied in a progressive recommendation scenario, providing recommendations for related items in a progressive manner, which can assist in providing more reliable diagnoses and herbal therapies for TCM clinical task.

Highly Robust Room-Temperature Interfacial Ferromagnetism in Ultrathin Co2Si Nanoplates.

The reduced dimensionality and interfacial effects in magnetic nanostructures open the feasibility to tailor magnetic ordering. Here, we report the synthesis of ultrathin metallic Co2Si nanoplates with a total thickness that is tunable to 2.2 nm. The interfacial magnetism coupled with the highly anisotropic nanoplate geometry leads to strong perpendicular magnetic anisotropy and robust hard ferromagnetism at room temperature, with a Curie temperature (TC) exceeding 950 K and a coercive field (HC) > 4.0 T at 3 K and 8750 Oe at 300 K. Theoretical calculations suggest that ferromagnetism originates from symmetry breaking and undercoordinated Co atoms at the Co2Si and SiO2 interface. With protection by the self-limiting intrinsic oxide, the interfacial ferromagnetism of the Co2Si nanoplates exhibits excellent environmental stability. The controllable growth of ambient stable Co2Si nanoplates as 2D hard ferromagnets could open exciting opportunities for fundamental studies and applications in Si-based spintronic devices.

Mitochondrial dysfunction and therapeutic perspectives in osteoporosis.

Osteoporosis (OP) is a systemic skeletal disorder characterized by reduced bone mass and structural deterioration of bone tissue, resulting in heightened vulnerability to fractures due to increased bone fragility. This condition primarily arises from an imbalance between the processes of bone resorption and formation. Mitochondrial dysfunction has been reported to potentially constitute one of the most crucial mechanisms influencing the pathogenesis of osteoporosis. In essence, mitochondria play a crucial role in maintaining the delicate equilibrium between bone formation and resorption, thereby ensuring optimal skeletal health. Nevertheless, disruption of this delicate balance can arise as a consequence of mitochondrial dysfunction. In dysfunctional mitochondria, the mitochondrial electron transport chain (ETC) becomes uncoupled, resulting in reduced ATP synthesis and increased generation of reactive oxygen species (ROS). Reinforcement of mitochondrial dysfunction is further exacerbated by the accumulation of aberrant mitochondria. In this review, we investigated and analyzed the correlation between mitochondrial dysfunction, encompassing mitochondrial DNA (mtDNA) alterations, oxidative phosphorylation (OXPHOS) impairment, mitophagy dysregulation, defects in mitochondrial biogenesis and dynamics, as well as excessive ROS accumulation, with regards to OP (Figure 1). Furthermore, we explore prospective strategies currently available for modulating mitochondria to ameliorate osteoporosis. Undoubtedly, certain therapeutic strategies still require further investigation to ensure their safety and efficacy as clinical treatments. However, from a mitochondrial perspective, the potential for establishing effective and safe therapeutic approaches for osteoporosis appears promising.

Low Temperature Synthesis of 2D p-Type α-In2Te3 with Fast and Broadband Photodetection.

2D A 2 III B 3 VI ${\mathrm{A}}_2^{{\mathrm{III}}}{\mathrm{B}}_3^{{\mathrm{VI}}}$ compounds (A = Al, Ga, In, and B = S, Se, and Te) with intrinsic structural defects offer significant opportunities for high-performance and functional devices. However, obtaining 2D atomic-thin nanoplates with non-layered structure on SiO2/Si substrate at low temperatures is rare, which hinders the study of their properties and applications at atomic-thin thickness limits. In this study, the synthesis of ultrathin, non-layered α-In2Te3 nanoplates is demonstrated using a BiOCl-assisted chemical vapor deposition method at a temperature below 350 °C on SiO2/Si substrate. Comprehensive characterization results confirm the high-quality single crystal is the low-temperature cubic phase α-In2Te3 , possessing a noncentrosymmetric defected ZnS structure with good second harmonic generation. Moreover, α-In2Te3 is revealed to be a p-type semiconductor with a direct and narrow bandgap value of 0.76 eV. The field effect transistor exhibits a high mobility of 18 cm2 V-1 s-1, and the photodetector demonstrates stable photoswitching behavior within a broadband photoresponse from 405 to 1064 nm, with a satisfactory response time of τrise = 1 ms. Notably, the α-In2Te3 nanoplates exhibit good stability against ambient environments. Together, these findings establish α-In2Te3 nanoplates as promising candidates for next-generation high-performance photonics and electronics.

Molecular Symmetry of Small-Molecule Passivating Agents Improves Crystal Quality of Perovskite Solar Cells.

Direct interaction with the defect sites of perovskite, functional groups have become the focal point of attention as passivating agents. However, the molecular parent nucleus determines the overall physical properties of the molecule, including the push-pull electronic characteristics of the functional groups, which poses significant challenges in terms of selectivity. Here, we discovered that the binary acid structure based on thiophene as the parent nucleus, due to changes in molecular symmetry, caused significant changes in the molecular dipole moment, resulting in significant changes in the passivation effects on under-coordinated Pb2+ in perovskite solar cells. For the axially symmetric thiophen-2,5-dicarboxylic acid (TPDC), the high dipole moment formed a concentrated surface negative potential on the carboxyl group, showing significant superiority over the centrally symmetric thieno[3,2-b] thiophene-2,5-dicarboxylic acid (TTDC) in forming high-quality perovskite crystals, suppressing charge recombination, enhancing effective charge transport, and raising internal electric fields. The power conversion efficiencies of the fully printable mesoscopic perovskite solar cells based on TPDC and TTDC were 17.15 % and 14.79 %, respectively, exhibiting important research value in the field of small molecule passivation mechanism research.

Metagenomic analysis of oral and intestinal microbiome of patients during the initial stage of orthodontic treatment.

INTRODUCTION: This prospective study analyzed changes in the oral and intestinal microbiomes in patients before and after fixed orthodontic treatment, elucidating the impacts of fixed orthodontic treatment on patient health and metabolism. METHODS: Metagenomic analysis was conducted on stool, dental plaque, and saliva samples from 10 fixed orthodontic patients. All the samples were sequenced with Illumina NovaSeq 6000 with a paired-end sequencing length of 150 bp. Identification of taxa in metagenomes and functional annotation of genes of the microbiota were performed using the data after quality control. Clinical periodontal parameters, including the gingiva index, plaque index, and pocket probing depth, were examined at each time point in triplicates. Patients also received a table to record their oral hygiene habits of brushing, flossing, and dessert consumption frequency over 1 month. RESULTS: The brushing and flossing times per day of patients were significantly increased after treatment compared with baseline. The number of times a patient ate dessert daily was also fewer after treatment than at baseline. In addition, the plaque index decreased significantly, whereas the pH value of saliva, gingiva index, and pocket probing depth did not change. No significant differences were observed between the participants before and after orthodontic treatment regarding alpha-diversity analysis of the gut, dental plaque, or saliva microbiota. However, on closer analysis, periodontal disease-associated bacteria levels in the oral cavity remain elevated. Alterations in gut microbiota were also observed after orthodontic treatment. CONCLUSIONS: The richness and diversity of the microbiome did not change significantly during the initial stage of fixed orthodontic treatment. However, the levels of periodontal disease-associated bacteria increased.

Citrin deficiency due to SLC25A13 exon deletion in a Chinese infant: A case report.

INTRODUCTION: Citrin is a calcium-bound aspartate-glutamate carrier protein encoded by the gene SLC25A13, mutations of which can cause citrin deficiency, an autosomal recessive disorder. The manifestations of citrin deficiency include neonatal intrahepatic choledeposits caused by citrin deficiency (NICCD: OMIM#605814), intermediate growth disorders and dyslipidemia caused by citrin deficiency, and citrullinemia type II (OMIM#603471) in adults. NICCD is a classical metabolic disorder that causes cholestasis in newborns. PATIENT CONCERN AND CLINICAL FINDINGS: Here, we present the case of a 2-month-old male patient treated in our hospital on March 20, 2023, due to "postnatal skin xanthochromia and transaminases higher than normal values". Since birth, the child's skin had yellowed all over the body, and his condition did not improve after multiple medical treatments. DIAGNOSIS/INTERVENTION/OUTCOMES: The child underwent full exome gene testing at the age of 2 months and 13 days, and the results indicated heterozygous deletion of exon 3 of the SLC25A13 gene, while genetic testing of the parents revealed no gene mutations. The variant was preliminarily judged as being pathogenic according to the ACMG guidelines, and the patient was diagnosed with "citrin deficiency". Skin yellowing eventually subsided, and liver function returned to normal without special treatment. CONCLUSIONS: Here, we report a rare case of citrin deficiency caused by a heterozygous deletion of the SLC25A13 gene. This case increases the clinical phenotypic profile of NICCD, suggesting that clinicians must be vigilant regarding such genetic metabolic diseases in the clinic for early diagnosis and treatment. NICCD should always be considered in the differential diagnosis of neonatal cholestasis.

Effect of insulin levels and plasma fasting glucose on refractive status in the United States population aged 12-19 years.

Purpose: The causes of myopia are varied, and both genetic and environmental influences play an essential role. The prevalence of myopia is increasing among adolescents and is expected to be more than one-third the global population by 2050. Some animal studies suggest that hyperinsulinemia may be a cause of myopia. In this context, the purpose of this paper is to investigate the potential effects of insulin levels and plasma fasting glucose on the refractive status of adolescents. Methods: Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. Weighted multivariable linear regression models were used to assess the effect of insulin levels, plasma fasting glucose on refractive status. We used a smooth curve fit to reveal the nonlinear relationship between the variables. Results: In the multivariate regression model, as insulin levels increased, there was a shift towards myopia in refractive status (ß = -0.013, 95% CI: -0.023 to -0.004). This correlation was also evident in the male adolescent subgroup (ß = -0.021, 95% CI: -0.035 to -0.007). Similar findings indicated that in Mexican Americans, there was a myopic shift in refractive status as insulin levels increased (ß = -0.018, 95% CI: -0.033 to -0.002). However, grouping by differences in insulin measurement showed no significant correlation in Mexican-Americans. At the same time, there was no significant correlation between plasma fasting glucose and refractive status (ß = -0.041, 95% CI: -0.174 to 0.091). Conclusion: The present cross-sectional study demonstrated that higher insulin levels may promote the development of myopia in adolescents, but there may be variations across gender and ethnicity. More basic research is needed to reveal the mechanistic reasons for the association.

Type-2 Diabetes Alters Hippocampal Neural Oscillations and Disrupts Synchrony between the Hippocampus and Cortex.

Type 2 diabetes mellitus (T2DM) increases the risk of neurological diseases, yet how brain oscillations change as age and T2DM interact is not well characterized. To delineate the age and diabetic effect on neurophysiology, we recorded local field potentials with multichannel electrodes spanning the somatosensory cortex and hippocampus (HPC) under urethane anesthesia in diabetic and normoglycemic control mice, at 200 and 400 days of age. We analyzed the signal power of brain oscillations, brain state, sharp wave associate ripples (SPW-Rs), and functional connectivity between the cortex and HPC. We found that while both age and T2DM were correlated with a breakdown in long-range functional connectivity and reduced neurogenesis in the dentate gyrus and subventricular zone, T2DM further slowed brain oscillations and reduced theta-gamma coupling. Age and T2DM also prolonged the duration of SPW-Rs and increased gamma power during SPW-R phase. Our results have identified potential electrophysiological substrates of hippocampal changes associated with T2DM and age. The perturbed brain oscillation features and diminished neurogenesis may underlie T2DM-accelerated cognitive impairment.