Quasi-critical dynamics in large-scale social systems regulated by sudden events.

How do heterogeneous individual behaviors arise in response to sudden events and how do they shape large-scale social dynamics? Based on a five-year naturalistic observation of individual purchasing behaviors, we extract the long-term consumption dynamics of diverse commodities from approximately 2.2 million purchase orders. We subdivide the consumption dynamics into trend, seasonal, and random components and analyze them using a renormalization group. We discover that the coronavirus pandemic, a sudden event acting on the social system, regulates the scaling and criticality of consumption dynamics. On a large time scale, the long-term dynamics of the system, regardless of arising from trend, seasonal, or random individual behaviors, is pushed toward a quasi-critical region between independent (i.e., the consumption behaviors of different commodities are irrelevant) and correlated (i.e., the consumption behaviors of different commodities are interrelated) phases as the pandemic erupts. On a small time scale, short-term consumption dynamics exhibits more diverse responses to the pandemic. While the trend and random behaviors of individuals are driven to quasi-criticality and exhibit scale-invariance as the pandemic breaks out, seasonal behaviors are more robust against regulations. Overall, these discoveries provide insights into how quasi-critical macroscopic dynamics emerges in heterogeneous social systems to enhance system reactivity to sudden events while there may exist specific system components maintaining robustness as a reflection of system stability.

Enzymatic characterization and dominant sites of foot-and-mouth disease virus 2C protein.

Foot-and-mouth disease virus (FMDV) 2C protein is a conserved non-structural protein and crucial for replication of the virus. In this study, FMDV 2C protein was prepared and the enzymatic activities were investigated in detail. The protein could digest ssDNA or ssRNA into a small fragment at about 10 nt, indicating that the protein has nuclease activity. But it did not show digestion to blunt-end dsDNA or dsRNA. The nuclease activity of 2C protein could be inhibited in 2 mM Zn2+ or Ca2+ while enhanced by Mg2+ or Mn2+. FMDV 2C protein exhibited unwinding activity to all the three kinds of dsDNA and dsRNA (5' protruded, 3' protruded, and blunt-end). The unwinding velocity to 5' protruded dsRNA was higher than to the blunt-end dsRNA. 2C protein only showed unwinding activity in high concentration of Mg2+, but no unwinding activity in physiological concentrations of Mg2+ and Ca2+, as well as in cell lysate. The 2C protein could catalyze two structured ssRNA to form double strand, thus it was proved to have RNA chaperone activity. The Mg2+ and ATP in different concentrations did not show promotion to the RNA chaperone activity. Finally, six mutant proteins (K116A, D160A, D170A, N207A, R226A, and F316A) were constructed and the enzymatic activities were analyzed. All the six mutations reduced the ATPase activity, D170A and F361A could inactivate the nuclease activity, while the N207A and F316A could inactivate the helicase activity. Our study provides a comprehensive understanding of the enzymatic activities of FMDV 2C protein.

Formononetin Alleviates Ischemic Acute Kidney Injury by Regulating Macrophage Polarization through KLF6/STAT3 Pathway.

Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-[Formula: see text], and IL-1[Formula: see text]) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula: see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.

Extraction of phenolic compounds from Moringa oleifera Lam. leaves with ultrasonic-assisted deep eutectic solvents.

Background: In this study, deep eutectic solvents (DESs) combined with ultrasound-assisted extraction (UAE) were used to extract bioactive compounds from the leaves of Moringa oleifera Lam. Methods: The FT-IR method was used to analyze the structural characteristics of the DESs, and the extraction efficiencies of the DESs for total phenolic content (TPC) and total flavonoid content (TFC) were evaluated. The stability of the extracts under high temperature and UV radiation was assessed, and their antioxidant activity was investigated after undergoing in vitro simulated digestion. Results: The results show that the seven DESs extracted more TPC and TFC than did the 70% ethanol (36.27 ± 1.58 mg GAE/g, 23.09 ± 1.47 mg RT/g), and the extraction process of UAE-DES was optimized by selecting choline chloride: citric acid as the DES solvent, which has the highest extraction of TPC (86.92 ± 1.34 mg GAE/g) and TFC (49.73 ± 0.85 mg RT/g). The stability results indicated that the DES phenolic extracts were less stable when exposed to high temperature and UV radiation, indicating that DES extracts have better bioactivity. Moreover, after in vitro simulated digestion, the DES extract shows a higher DPPH free radical scavenging capacity (12.79 ± 3.88 mmol Trolox/g of DES extracts, 6.99 ± 4.02 mmol Trolox/g of ethanol extracts) and ferric ion reducing antioxidant power (62.61 ± 1.71 mmol Trolox/g of DES extracts, 55.07 ± 1.66 mmol Trolox/g of ethanol extracts) than ethanol extracts. Conclusion: This study confirmed that DESs are a new and environmentally friendly solvent that can be used for the extraction of phenolic compounds.

The relationship between system inflammation response index and coronary heart disease: a cross-sectional study (NHANES 2007-2016).

Background: Coronary heart disease (CHD) is one of the common chronic diseases in clinical practice, often accompanied by inflammatory reactions. In recent years, the system inflammation response index (SIRI) has aroused researchers' interest as a novel inflammatory biomarker. This study aims to explore the relationship between the SIRI and CHD through the National Health and Nutrition Examination Survey (NHANES) database. Methods: We conducted a cross-sectional study and analyzed participants aged 40 and above with complete data from the NHANES survey years 2007-2016. Logistic regression analysis was used in this study to explore the relationship between the risk of CHD and SIRI. Stratified subgroup analysis was conducted based on age, gender, race, education level, body mass index (BMI), smoking status, drinking, hypertension, diabetes and angina pectoris to evaluate the relationship between SIRI and CHD in different populations. Additionally, restricted cubic spline (RCS) analysis was employed to investigate whether there is a nonlinear association between SIRI and CHD. Results: A total of 6374 eligible participants were included, among whom 387 were diagnosed with CHD. The SIRI levels in the CHD group were significantly higher than those in the non-CHD group. After adjusting for potential confounders, an elevated SIRI level was associated with an increased risk of CHD, with an odds ratio of 1.12, 95% CI: (1.03, 1.22), P = 0.008. Subgroup analysis results indicated a significant interaction between SIRI and CHD among genders (P for interaction <0.05), especially in females. In contrast, no significant interaction was observed among age, race, education level, BMI, smoking status, drinking, hypertension, diabetes and angina pectoris (P for interaction >0.05). The RCS analysis showed a significant linear relationship between SIRI and CHD (P for non-linearity >0.05), with an inflection point at 2.86. Conclusion: Our study indicates that an elevated system inflammation response index is associated with a higher risk of CHD. Particularly among women.

Network model with internal complexity bridges artificial intelligence and neuroscience.

Artificial intelligence (AI) researchers currently believe that the main approach to building more general model problems is the big AI model, where existing neural networks are becoming deeper, larger and wider. We term this the big model with external complexity approach. In this work we argue that there is another approach called small model with internal complexity, which can be used to find a suitable path of incorporating rich properties into neurons to construct larger and more efficient AI models. We uncover that one has to increase the scale of the network externally to stimulate the same dynamical properties. To illustrate this, we build a Hodgkin-Huxley (HH) network with rich internal complexity, where each neuron is an HH model, and prove that the dynamical properties and performance of the HH network can be equivalent to a bigger leaky integrate-and-fire (LIF) network, where each neuron is a LIF neuron with simple internal complexity.

Impact of Physiological Characteristics on Chylomicron Pathway-Mediated Absorption of Nanocrystals in the Pediatric Population.

Nanocrystals exhibit significant advantages in improving the oral bioavailability of poorly soluble drugs. However, the complicated absorption properties of nanocrystals and the differences in physiological characteristics between children and adults limit pediatric applications of nanocrystals. To elucidate the absorption differences and the underlying mechanisms between children and adults, the pharmacokinetics and tissue distribution of aprepitant crystals with different particle sizes (NC200, NC500, and MC2.5) in rats and mice at different ages were studied, and their absorption mechanisms were investigated in Caco-2 cells, mice, and rats. It was found that childhood animals demonstrated higher bioavailability compared with adolescent and adult animals, which was related to higher bile salt concentration and accelerated drug dissolution in the intestine of childhood animals. The majority of nanocrystals were dissolved and formed micelles under the influence of bile salts. Compared with intact nanocrystals, the bile salt micelle-associated aprepitant was absorbed through the chylomicron pathway, wherein Apo B assisted in the reassembling of the aprepitant micelles after endocytosis. Higher bile salt concentration and Apo B expression in the intestines of childhood animals are both responsible for the higher chylomicron transport pathways. Elucidation of the chylomicron pathway in the varied absorption of nanocrystals among children, adolescents, and adults provides strong theoretical guidance for promoting the rational and safe use of nanocrystals in pediatric populations.

Structure, rheology and stability of walnut oleogels with different carboxylation degree of cellulose nanofiber.

The effects of carboxylation degree (0.3-2.4 mmol/g) of cellulose nanofiber (CNF) on the microstructure and mechanical properties of edible walnut oleogels were comprehensively examined. The oleogels were well prepared by emulsion-templated approach for potential substitute of conventional saturated or trans-fats in food products. The results demonstrated that the oil-binding capacity (OBC) and textural strength of oleogels enhanced with the increase of CNF carboxyl content, while the structural strength (G' in rheological measurement) and the resistance to shear thinning was first decreased and then increased. It possibly reflected the competition on the dominant structuring mechanism by hydrogen bonding from cellulose hydroxyl groups and electrostatic interactions from -COONa function. With the combined mechanism, oleogel with low structural strength and relatively high OBC (CNF carboxyl content of 1.2 mmol/g, OBC >83 %, G' ≈ 7 × 104 Pa and firmness of 0.30 N) and oleogel with enough structural rigidity and high OBC (CNF carboxyl content of 1.8 mmol/g, OBC >89 %, G' of up to 1.7 × 105 Pa, and firmness of up to 0.66 N) were both fabricated. This reveals the feasibility of regulating oleogel structure and textual properties by using CNF as the unique oleogelator and simply changing its surface carboxyl function.

Childhood Adiposity and Risk of Major Clinical Heart Diseases in Adulthood: A Mendelian Randomization Study.

BACKGROUND: The causal relationship between childhood adiposity and adult risk of heart diseases has not been clearly demonstrated. This study aims to ascertain whether genetically predicted childhood body mass index (BMI) and childhood obesity are causally associated with adult coronary heart disease, myocardial infarction, heart failure, atrial fibrillation, hypertrophic cardiomyopathy, and pulmonary heart disease. METHODS AND RESULTS: To investigate the causative relationships and underlying mechanisms between childhood adiposity and adult heart diseases, 3 main methods of Mendelian randomization were used: 2-sample Mendelian randomization, multivariable Mendelian randomization with controlling for several cardiometabolic risk variables, and mediation analysis. Every 1-SD rise in genetically predicted childhood body mass index was associated with 24% (odds ratio [OR], 1.24 [95% CI, 1.12-1.37]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), and 27% (OR, 1.27 [95% CI, 1.04-1.49]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. Every 1-unit increase in log-odds in childhood obesity was associated with 11% (OR, 1.11 [95% CI, 1.06-1.16]), 14% (OR, 1.14 [95% CI, 1.04-1.23]), 10% (OR, 1.10 [95% CI, 1.03-1.18]), and 20% (OR, 1.20 [95% CI, 1.08-1.32]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. The link between childhood adiposity and adult heart diseases was found to be mediated by high-density lipoprotein cholesterol, triglyceride, hypertension, and type 2 diabetes. CONCLUSIONS: Our findings support the causal relationships between childhood adiposity and risk of adult coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation. Blood lipids, hypertension, and type 2 diabetes are factors that mediate the aforementioned associations.

A simplex path integral and a simplex renormalization group for high-order interactions.

Modern theories of phase transitions and scale invariance are rooted in path integral formulation and renormalization groups (RGs). Despite the applicability of these approaches in simple systems with only pairwise interactions, they are less effective in complex systems with undecomposable high-order interactions (i.e. interactions among arbitrary sets of units). To precisely characterize the universality of high-order interacting systems, we propose a simplex path integral and a simplex RG (SRG) as the generalizations of classic approaches to arbitrary high-order and heterogeneous interactions. We first formalize the trajectories of units governed by high-order interactions to define path integrals on corresponding simplices based on a high-order propagator. Then, we develop a method to integrate out short-range high-order interactions in the momentum space, accompanied by a coarse graining procedure functioning on the simplex structure generated by high-order interactions. The proposed SRG, equipped with a divide-and-conquer framework, can deal with the absence of ergodicity arising from the sparse distribution of high-order interactions and can renormalize a system with intertwined high-order interactions at thep-order according to its properties at theq-order (p⩽q). The associated scaling relation and its corollaries provide support to differentiate among scale-invariant, weakly scale-invariant, and scale-dependent systems across different orders. We validate our theory in multi-order scale-invariance verification, topological invariance discovery, organizational structure identification, and information bottleneck analysis. These experiments demonstrate the capability of our theory to identify intrinsic statistical and topological properties of high-order interacting systems during system reduction.

Equisetin protects from atherosclerosis in vivo by binding to STAT3 and inhibiting its activity.

Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.

A highly sensitive and colorimetric fluorescent probe for visualizing hydroxylamine in immune cells.

BACKGROUND: Hydroxylamine (HA) is vital industrial raw material and pharmaceutical intermediate. In addition, HA is an important cellular metabolite, which is intermediate in the formation of nitric oxide and nitroxide. However, excessive amounts of HA are toxic to both animals and plants. Conventional methods for the detection of HA are cumbersome and complicated. The detection of HA with fluorescent probes is convenient and sensitive. There are few probes available for the detection of hydroxylamine. Therefore, a fluorescent probe for the sensitive and selective detection of HA was developed in this work. RESULTS: A coumarin derivative SWJT-22 was synthesized as a colorimetric fluorescent probe to detect hydroxylamine (HA), with high sensitivity and selectivity. The detection limit of the probe to HA was 0.15 µM, which was lower than most probes of HA. Upon the addition of HA to aqueous solution containing SWJT-22, the color of the solution changed from orange to yellow, and the fluorescence color also changed from orange to green. The reaction mechanism of SWJT-22 to HA was confirmed by 1H NMR titrations, mass spectrometry and round bottom flask experiments. Moreover, SWJT-22 had been fabricated into portable test strips for the detection of HA. SWJT-22 had been successfully used in cellular imaging and could detect both endogenous and exogenous HA in HeLa cells and RAW 264.7 cells. SIGNIFICANCE: Due to the physiological role of hydroxylamine in organisms, it is crucial to detect hydroxylamine selectively and sensitively. This work provided a convenient tool for the detection of hydroxylamine, not only to detect endogenous and exogenous HA in cells, but also made into portable test strips. The HA fluorescent probe SWJT-22 is expected to promote the study of HA in physiological processes.

The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease often accompanied by low-grade inflammation. Recently, the neutrophil-to-lymphocyte ratio (NLR) has garnered researchers' interest as an emerging inflammation biomarker. This study aimed to comprehensively explore the relationship between NLR and T2DM using the National Health and Nutrition Examination Survey (NHANES) database. METHOD: We employed a cross-sectional study design to analyze data from five NHANES cycles from 2007 to 2016, excluding individuals with incomplete data. This study utilized a weighted logistic regression model, subgroup analyses, and restricted cubic spline (RCS) analysis to assess the potential relationship between NLR and T2DM. RESULTS: A total of 9903 participants were eligible for the analysis, of which 1280 were diagnosed with T2DM. The T2DM group exhibited significantly higher NLR levels than the non-T2DM group. After adjusting for potential confounders, elevated NLR levels were associated with an increased risk of developing T2DM, indicated by an odds ratio (OR) of 1.14, 95% CI: (1.05,1.24), P = 0.003. The results of the subgroup analyses revealed a significant interaction effect between NLR and T2DM concerning race and hypertension (P for interaction < 0.05). In contrast, no significant interactions were found for age, sex, education level, body mass index (BMI), smoking status, recreational activities, and alcohol drinker (P for interaction > 0.05). RCS analysis showed a significant non-linear relationship between NLR and T2DM, with an inflection point at 2.27 (all P for non-linearity < 0.05). CONCLUSION: Our study indicates that an elevated neutrophil-to-lymphocyte ratio is associated with a higher risk of T2DM.

Degradation of emerging contaminants in synthetic hydrolyzed urine by UV/peracetic acid: Free radical chemistry, and toxicity analysis.

The ecological impact of emerging contaminants (ECs) in aquatic environments has raised concerns, particularly with regards to urine as a significant source of such contaminants in wastewater. The current investigation used the UV/Peracetic Acid (UV/PAA) processes, an innovative advanced oxidation technology, to effectively separate two emerging pollutants from urine at its source, namely, ciprofloxacin (CIP) and bisphenol A(BPA). The research findings demonstrate that the presence of the majority of characteristic ions has minimal impact on the degradation of ECs. However, in synthetic hydrolyzed urine, only NH4+ inhibits the degradation of two types of ECs, with a more pronounced effect observed on CIP degradation compared to BPA.The impact of halogen ions, specifically Cl- and I-, on the degradation of CIP in synthetic hydrolyzed urine was a complex phenomenon. When these two halogen ions are present individually, the generation of reactive halogen species (RHS) within the system enhances the degradation of CIP. However, when both types of ions coexist, the formation of diatomic radical species partially inhibits degradation. In terms of BPA degradation, while the production of reactive chlorine species (RCS) to some extent hinders the reaction rate, the generation of reactive iodine species (RIS) promotes the overall process. CIP undergoes fragmentation of the piperazine and quinoline rings, decarboxylation, defluorination reactions, as well as substitution reactions, leading to the formation of products with simplified structures. The degradation of BPA occurs gradually through hydroxyl and halogen substitution as well as isopropyl cleavage. The preliminary toxicity analysis confirmed that the presence of halogen ions in urine resulted in the formation of halogenated products in two types of ECs, albeit with an overall reduction in toxicity. The UV/PAA processes was considered to be an effective and relatively safe approach for the separation of ECs in urine.

Peritoneal fluid indocyanine green test for diagnosis of gut leakage in anastomotic leakage rats and colorectal surgery patients.

BACKGROUND: Application of indocyanine green (ICG) fluorescence has led to new developments in gastrointestinal surgery. However, little is known about the use of ICG for the diagnosis of postoperative gut leakage (GL). In addition, there is a lack of rapid and intuitive methods to definitively diagnose postoperative GL. AIM: To investigate the effect of ICG in the diagnosis of anastomotic leakage in a surgical rat GL model and evaluate its diagnostic value in colorectal surgery patients. METHODS: Sixteen rats were divided into two groups: GL group (n = 8) and sham group (n = 8). Approximately 0.5 mL of ICG (2.5 mg/mL) was intravenously injected postoperatively. The peritoneal fluid was collected for the fluorescence test at 24 and 48 h. Six patients with rectal cancer who had undergone laparoscopic rectal cancer resection plus enterostomies were injected with 10 mL of ICG (2.5 mg/mL) on postoperative day 1. Their ostomy fluids were collected 24 h after ICG injection to identify the possibility of the ICG excreting from the peripheral veins to the enterostomy stoma. Participants who had undergone colectomy or rectal cancer resection were enrolled in the diagnostic test. The peritoneal fluids from drainage were collected 24 h after ICG injection. The ICG fluorescence test was conducted using OptoMedic endoscopy along with a near-infrared fluorescent imaging system. RESULTS: The peritoneal fluids from the GL group showed ICG-dependent green fluorescence in contrast to the sham group. Six samples of ostomy fluids showed green fluorescence, indicating the possibility of ICG excreting from the peripheral veins to the enterostomy stoma in patients. The peritoneal fluid ICG test exhibited a sensitivity of 100% and a specificity of 83.3% for the diagnosis of GL. The positive predictive value was 71.4%, while the negative predictive value was 100%. The likelihood ratios were 6.0 for a positive test result and 0 for a negative result. CONCLUSION: The postoperative ICG test in a drainage tube is a valuable and simple technique for the diagnosis of GL. Hence, it should be employed in clinical settings in patients with suspected GL.

Defined synthetic microbial communities colonize and benefit field-grown sorghum.

The rhizosphere constitutes a dynamic interface between plant hosts and their associated microbial communities. Despite the acknowledged potential for enhancing plant fitness by manipulating the rhizosphere, the engineering of the rhizosphere microbiome through inoculation has posed significant challenges. These challenges are thought to arise from the competitive microbial ecosystem where introduced microbes must survive, and the absence of adaptation to the specific metabolic and environmental demands of the rhizosphere. Here, we engineered a synthetic rhizosphere community (SRC1) with the anticipation that it would exhibit a selective advantage in colonizing the host Sorghum bicolor, thereby potentially fostering its growth. SRC1 was assembled from bacterial isolates identified either for their potential role in community cohesion through network analysis or for their ability to benefit from host-specific exudate compounds. The growth performance of SRC1 was assessed in vitro on solid media, in planta under gnotobiotic laboratory conditions, and in the field. Our findings reveal that SRC1 cohesion is most robust when cultivated in the presence of the plant host under laboratory conditions, with lineages being lost from the community when grown either in vitro or in a native field setting. We establish that SRC1 effectively promotes the growth of both above- and below-ground plant phenotypes in both laboratory and native field contexts. Furthermore, in laboratory conditions, these growth enhancements correlate with the transcriptional dampening of lignin biosynthesis in the host. Collectively, these results underscore the potential utility of synthetic microbial communities for modulating crop performance in controlled and native environments alike.

[Analysis of a child with developmental disorder and epilepsy due to a homozygous variant of SLC25A12 gene].

OBJECTIVE: To explore the genetic basis for a child featuring global developmental delay and epilepsy. METHODS: A child who had presented at Guangzhou Women and Children's Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c.115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+PM3_Supporting+PP3_Moderate+PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product. CONCLUSION: The homozygous c.115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.

A retrospective analysis of lymph node dissection in Siewert II adenocarcinoma of the esophagogastric junction.

BACKGROUND: Analyze the pattern of lymph node metastasis in Siewert II adenocarcinoma of the esophagogastric junction (AEG) and provide a basis for the principles of surgical access. METHODS: The clinical data of 112 Siewert type II AEG patients admitted to the Fifth Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from 2020 to 2022 were retrospectively collected. The probability of lymph node metastasis in each site and the clearance rate of lymph nodes in each site by different surgical approaches were analyzed. RESULTS: The lymph node metastasis rates in the middle and upper mediastinum group, the lower mediastinum group, the upper perigastric + supra pancreatic group, and the lower perigastric + hepatoduodenal group were 0.0%, 5.4%, 61.6%, and 17.1%, (P < 0.001). The number of lymph nodes cleared in the middle and upper mediastinum group was 0.00, 0.00, 4.00 in the transabdominal approach (TA), left thoracic approach (LT), and Ivor-Lewis (IL) group, (P < 0.001); The number of lymph nodes cleared in the lower mediastinal group was 0.00, 2.00, 2.00, (P < 0.001); The number of lymph node dissection in the perigastric + hepatoduodenal group was 3.00, 0.00, and 8.00, (P < 0.001). The overall complication rates were 25.7%, 12.5%, and 36.4%, (P = 0.058). CONCLUSION: Siewert II AEG has the highest rate of lymph node metastasis in the upper perigastric + supra-pancreatic region, followed by the lower perigastric + hepatoduodenal, lower mediastinal, middle, and upper mediastinal regions. Ivor-Lewis can be used for both thoracic and abdominal lymph node dissection and does not increase the incidence of postoperative complications.

Fast-Responsive HClO-Activated Near-Infrared Fluorescent Probe for In Vivo Diagnosis of Inflammatory Bowel Disease and Ex Vivo Optical Fecal Analysis.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease, whose etiology is intimately related to the overproduction of hypochlorous acid (HClO). Optical monitoring of HClO in the living body favors real-time diagnosis of inflammatory diseases. However, HClO-activated near-infrared (NIR) fluorescent probes with rapid response and high inflammatory cell uptake are still lacking. Herein, we report an activatable acceptor-π-acceptor (A-π-A)-type NIR fluorescent probe (Cy-DM) bearing two d-mannosamine groups for the sensitive detection of HClO in early IBD and stool testing. Once reacted with HClO, nonfluorescent Cy-DM could be turned on within 2 s by generating a donor-π-acceptor (D-π-A) structure due to the enhanced intramolecular charge transfer mechanism, showing intense NIR fluorescence emission at 700 nm and a large Stokes shift of 115 nm. Moreover, it was able to sensitively and selectively image exogenous and endogenous HClO in the lysosomes of living cells with a detection limit of 0.84 µM. More importantly, because of the d-mannosamine modification, Cy-DM was efficiently taken up by inflammatory cells in the intestine after intravenous administration, allowing noninvasive visualization of endogenous HClO in a lipopolysaccharide-induced IBD mouse model with a high fluorescence contrast of 6.8/1. In addition, water-soluble Cy-DM has also been successfully applied in ex vivo optical fecal analysis, exhibiting a 3.4-fold higher fluorescence intensity in the feces excreted by IBD mice. We believe that Cy-DM is promising as an invaluable tool for rapid diagnosis of HClO-related diseases as well as stool testing.

Immunogenicity and safety of a self-assembling ZIKV nanoparticle vaccine in mice.

Zika virus (ZIKV) is a mosquito-borne flavivirus that highly susceptibly causes Guillain-Barré syndrome and microcephaly in newborns. Vaccination is one of the most effective measures for preventing infectious diseases. However, there is currently no approved vaccine to prevent ZIKV infection. Here, we developed nanoparticle (NP) vaccines by covalently conjugating self-assembled 24-subunit ferritin to the envelope structural protein subunit of ZIKV to achieve antigen polyaggregation. The immunogenicityof the NP vaccine was evaluated in mice. Compared to monomer vaccines, the NP vaccine achieved effective antigen presentation, promoted the differentiation of follicular T helper cells in lymph nodes, and induced significantly greater antigen-specific humoral and cellular immune responses. Moreover, the NP vaccine enhanced high-affinity antigen-specific IgG antibody levels, increased secretion of the cytokines IL-4 and IFN-γ by splenocytes, significantly activated T/B lymphocytes, and improved the generation of memory T/B cells. In addition, no significant adverse reactions occurred when NP vaccine was combined with adjuvants. Overall, ferritin-based NP vaccines are safe and effective ZIKV vaccine candidates.