A pseudo-targeted metabolomics for discovery of potential biomarkers of cardiac hypertrophy in rats.

Cardiac hypertrophy (CH) is one of the stages in the occurrence and development of severe cardiovascular diseases, and exploring its biomarkers is beneficial for delaying the progression of severe cardiovascular diseases. In this research, we established a comprehensive and highly efficient pseudotargeted metabolomics method, which demonstrated a superior capacity to identify differential metabolites when compared to traditionaluntargeted metabolomics. The intra/inter-day precision and reproducibility results proved the method is reliable and precise. The established method was then applied to seek the potential differentiated metabolic biomarkers of cardiac hypertrophy (CH) rats, and oxylipins, phosphorylcholine (PC), lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), Krebs cycle intermediates, carnitines, amino acids, and bile acids were disclosed to be the possible differentiate components. Their metabolic pathway analysis revealed that the potential metabolic alterations in CH rats were mainly associated with phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, citrate cycle, glyoxylate and dicarboxylate metabolism, and tyrosine metabolism. In sum, this research provided a comprehensiveand reliable LC-MS/MS MRM platform for pseudo-targeted metabolomics investigation of disease condition, and some interesting potential biomarkers were disclosed for CH, which merit further exploration in the future.

A domain knowledge-based interpretable deep learning system for improving clinical breast ultrasound diagnosis.

BACKGROUND: Though deep learning has consistently demonstrated advantages in the automatic interpretation of breast ultrasound images, its black-box nature hinders potential interactions with radiologists, posing obstacles for clinical deployment. METHODS: We proposed a domain knowledge-based interpretable deep learning system for improving breast cancer risk prediction via paired multimodal ultrasound images. The deep learning system was developed on 4320 multimodal breast ultrasound images of 1440 biopsy-confirmed lesions from 1348 prospectively enrolled patients across two hospitals between August 2019 and December 2022. The lesions were allocated to 70% training cohort, 10% validation cohort, and 20% test cohort based on case recruitment date. RESULTS: Here, we show that the interpretable deep learning system can predict breast cancer risk as accurately as experienced radiologists, with an area under the receiver operating characteristic curve of 0.902 (95% confidence interval = 0.882 - 0.921), sensitivity of 75.2%, and specificity of 91.8% on the test cohort. With the aid of the deep learning system, particularly its inherent explainable features, junior radiologists tend to achieve better clinical outcomes, while senior radiologists experience increased confidence levels. Multimodal ultrasound images augmented with domain knowledge-based reasoning cues enable an effective human-machine collaboration at a high level of prediction performance. CONCLUSIONS: Such a clinically applicable deep learning system may be incorporated into future breast cancer screening and support assisted or second-read workflows.

Breast cancer is one of the most common cancers, and finding it early can greatly improve patients' chances of survival and recovery. We create a tool based on artificial intelligence (AI)­whereby computer software learns to perform tasks that normally require human thinking­called MUP-Net. MUP-Net can analyze medical images to predict a patient's risk of having breast cancer. To make this AI tool usable in clinical practice, we enabled doctors to see the reasoning behind the AI's predictions by visualizing the key image features it analyzed. We showed that our AI tool not only makes doctors more confident in their diagnosis but also helps them make better decisions, especially for less experienced doctors. With further testing, our AI tool may help clinicians to diagnose breast cancer more accurately and quickly, potentially improving patient outcomes.

Down-regulation of O-GlcNAcylation alleviates insulin signaling pathway impairment following arsenic exposure via suppressing the AMPK/mTOR-autophagy pathway.

Impairment of the insulin signaling pathway is a key contributor to insulin resistance under arsenic exposure. Specifically, O-GlcNAcylation, an important post-translational modification, plays a crucial role in insulin resistance. Nevertheless, the concrete effect and mechanism of O-GlcNAcylation in arsenic-induced impairment of the insulin signaling pathway remain elusive. Herein, C57BL/6 mice were continuously fed arsenic-containing food, with a total arsenic concentration of 30 mg/kg. We observed that the IRS/Akt/GSK-3ß insulin signaling pathway was impaired, and autophagy was activated in mouse livers and HepG2 cells exposed to arsenic. Additionally, O-GlcNAcylation expression in mouse livers and HepG2 cells was elevated, and the key O-GlcNAcylation homeostasis enzyme, O-GlcNAc transferase (OGT), was upregulated. In vitro, non-targeted metabolomic analysis showed that metabolic disorder was induced, and inhibition of O-GlcNAcylation restored the metabolic profile of HepG2 cells exposed to arsenic. In addition, we found that the compromised insulin signaling pathway was dependent on AMPK activation. Inhibition of AMPK mitigated autophagy activation and impairment of insulin signaling pathway under arsenic exposure. Furthermore, down-regulation of O-GlcNAcylation inhibited AMPK activation, thereby suppressing autophagy activation, and improving the impaired insulin signaling pathway. Collectively, our findings indicate that arsenic can impair the insulin signaling pathway by regulating O-GlcNAcylation homeostasis. Importantly, O-GlcNAcylation inhibition alleviated the impaired insulin signaling pathway by suppressing the AMPK/mTOR-autophagy pathway. This indicates that regulating O-GlcNAcylation may be a potential intervention for the impaired insulin signaling pathway induced by arsenic.

Diagnosis and management of intraspinal tuberculoma with osseous involvement: a case report.

Introduction and importance: Intraspinal tuberculoma is rare and challenging situation, which results in serious neurological dysfunctions. Case presentation: This case report shows an intraspinal tuberculoma with osseous involvement in a 31-year-old male patient with subacute progressing neurologic deficit. His medical history included tuberculosis of pulmonary and intestinal 8 years previously, at which time he had been treated with intestinal obstruction operation and antituberculosis treatment. A quadruple antituberculosis treatment was carried out after admission; however, his neurological condition was steadily worsening. He underwent debulking of mass for decompression and pathological analysis revealed intraspinal tuberculoma. The patient was prescribed a 12-month course of antituberculosis therapy, and a good clinical outcome was obtained subsequently. Clinical discussion: This case was treated by microsurgical resection and antituberculosis therapy, and the outcome was favourable. Conclusion: Intraspinal tuberculoma should be considered when an intraspinal mass is found with a history of tuberculosis, it can be effectively diagnosed by MRI and treated by the combination of medical and surgical treatments.

Interfacial modulation of hollow ZnS-SnS2 microboxs by Ti3C2Tx MXene to construct three-dimensional hybrid anodes for lithium-ion batteries with ultra high stability at low temperature.

Metal sulfides exhibit obvious volume expansion due to the inherent poor conductivity and large temperature fluctuations, leading to reduced storage capacity. Herein, an electrostatic self-assembly strategy was proposed to fabricate a three-dimensional (3D) polyaniline (PANI) encapsulated hollow ZnS-SnS2 (H-ZSS) heterojunction confined on Ti3C2Tx MXene nanosheets (H-ZnS-SnS2@MXene@PANI, denoted as H-ZSSMP), which exhibits remarkable reversible capacity and cyclic stability (520.3 mAh/g at 2 A/g after 1000 cycles) at room temperature. Additionally, specific capacity can stabilized at 362.5 mAh/g for 250 cycles at -20 °C. A full cell with the configuration of H-ZSSMP//lithium iron phosphate (LiFePO4) can retain a satisfactory reversible capacity of 424.7 mAh/g after 100 cycles at 0.1 C. Theory calculations confirm heterogeneous interface can accelerate the transfer of ions through the interfacial regulation effect of MXene on H-ZSS. Our work provides a simple strategy to improve the capacity and stability of lithium-ion batteries (LIBs), as well as the new applications of MXene and bimetallic sulfides as anode materials, which will facilitate the development of MXene based composites for energy storage.

Continuous microalgal culture module and method of culturing microalgae containing macular pigment.

This study established and investigated continuous macular pigment (MP) production with a lutein (L):zeaxanthin (Z) ratio of 4-5:1 by an MP-rich Chlorella sp. CN6 mutant strain in a continuous microalgal culture module. Chlorella sp. CN6 was cultured in a four-stage module for 10 days. The microalgal culture volume increased to 200 L in the first stage (6 days). Biomass productivity increased to 0.931 g/L/day with continuous indoor white light irradiation during the second stage (3 days). MP content effectively increased to 8.29 mg/g upon continuous, indoor white light and blue light-emitting diode irradiation in the third stage (1 day), and the microalgal biomass and MP concentrations were 8.88 g/L and 73.6 mg/L in the fourth stage, respectively. Using a two-step MP extraction process, 80 % of the MP was recovered with a high purity of 93 %, and its L:Z ratio was 4-5:1.

Establishing national reference materials for genetic testing of cytochrome P450.

OBJECTIVES: Reference materials for in-vitro diagnostic reagents play a critical role in determining the quality of reagents and ensuring the accuracy of clinical test results. This study aimed to establish a national reference material (NRM) for detecting cytochrome P450 (CYP) genes related to drug metabolism by screening databases on the Chinese population to identify CYP gene polymorphism characteristics. METHODS: To prepare the NRM, we used DNA extracted from healthy human immortalized B lymphoblastoid cell lines as the raw material. Samples of these cell lines were obtained from the Chinese Population PGx Gene Polymorphism Biobank. Further, we used Sanger sequencing, next-generation sequencing, and commercial assay kits to validate the polymorphic genotypes. RESULTS: Among the CYP superfamily genes, we confirmed 24 riboswitch loci related to drug metabolism, with evidence levels of 1A, 2A, 3, and 4. We confirmed the polymorphic loci and validated their genotypes using various sequencing techniques. Our results were consistent with the polymorphism information of samples obtained from the biobank, thus demonstrating high precision and stability of the established NRM. CONCLUSION: An NRM (360 056-202 201) for CYP genetic testing covering 24 loci related to drug metabolism was established and approved to assess in-vitro diagnostic reagents containing CYP family gene polymorphisms and perform clinical inter-room quality evaluations.

Identification, diversity, and evolution analysis of Commd gene family in Haliotis discus hannai and immune response to biotic and abiotic stresses.

The Commd (Copper Metabolism gene MURR1 Domain) family genes play crucial roles in various biological processes, including copper and sodium transport regulation, NF-κB activity, and cell cycle progression. Their function in Haliotis discus hannai, however, remains unclear. This study focused on identifying and analyzing the Commd genes in H. discus hannai, including their gene structure, phylogenetic relationships, expression profiles, sequence diversity, and alternative splicing. The results revealed significant homology between H. discus hannai's Commd genes and those of other mollusks. Both transcriptome quantitative analysis and qRT-PCR demonstrated the responsiveness of these genes to heat stress and Vibrio parahaemolyticus infection. Notably, alternative splicing analysis revealed that COMMD2, COMMD4, COMMD5, and COMMD7 produce multiple alternative splice variants. Furthermore, sequence diversity analysis uncovered numerous missense mutations, specifically 9 in COMMD5 and 14 in COMMD10. These findings contribute to expanding knowledge on the function and evolution of the Commd gene family and underscore the potential role of COMMD in the innate immune response of H. discus hannai. This research, therefore, offers a novel perspective on the molecular mechanisms underpinning the involvement of Commd genes in innate immunity, paving the way for further explorations in this field.

Association between metabolic reprogramming and immune regulation in digestive tract tumors.

BACKGROUND: The cancers of the digestive tract, including colorectal cancer (CRC), gastric cancer (GC) and Esophageal cancer (ESCA), are part of the most common cancers as well as one of the most important leading causes of cancer death worldwide. SUMMARY: Despite the emergence of immune checkpoint inhibitors (e.g., anti-CTLA-4 and anti-PD-1/PD-L1) in the past decade, offering renewed optimism in cancer treatment, only a fraction of patients derive benefit from these therapies. This limited efficacy may stem from tumor heterogeneity and the impact of metabolic reprogramming on both tumor cells and immune cells within the tumor microenvironment (TME). The metabolic reprogramming of glucose, lipids, amino acids, and other nutrients represents a pivotal hallmark of cancer, serving to generate energy, reducing-equivalent and biological macromolecule, thereby fostering tumor proliferation and invasion. Significantly, the metabolic reprogramming of tumor cells can orchestrate changes within the TME, rendering patients unresponsive to immunotherapy. KEY MESSAGES: In this review, we predominantly encapsulate recent strides on metabolic reprogramming among digestive tract cancer, especially CRC, in the TME with a focus on how these alterations influence antitumor immunity. Additionally, we deliberate on potential strategies to address these abnormities in metabolic pathways and the viability of combined therapy within the realm of anticancer immunotherapy.

Inhibition of autophagy-related protein 7 enhances anti-tumor immune response and improves efficacy of immune checkpoint blockade in microsatellite instability colorectal cancer.

BACKGROUND: The efficacy of anti-PD-1 therapy is primarily hindered by the limited T-cell immune response rate and immune evasion capacity of tumor cells. Autophagy-related protein 7 (ATG7) plays an important role in autophagy and it has been linked to cancer. However, the role of ATG7 in the effect of immune checkpoint blockade (ICB) treatment on high microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) CRC is still poorly understood. METHODS: In this study, patients from the cancer genome altas (TCGA) COAD/READ cohorts were used to investigate the biological mechanism driving ATG7 development. Several assays were conducted including the colony formation, cell viability, qRT-PCR, western blot, immunofluorescence, flow cytometry, ELISA, immunohistochemistry staining and in vivo tumorigenicity tests. RESULTS: We found that ATG7 plays a crucial role in MSI-H CRC. Its knockdown decreased tumor growth and caused an infiltration of CD8+ T effector cells in vivo. ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Meanwhile, ATG7 inhibition also suppressed cholesterol accumulation and augmentation of anti-tumor immune responses. Combining ATG7 inhibition and statins improved the therapeutic benefit of anti-PD-1 in MSI-H CRC. Importantly, CRC patients with high expression of both ATG7 and recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) experienced worse prognosis compared to those with low ATG7 and HMGCR expression. CONCLUSIONS: Inhibition of ATG7 leads to upregulation of MHC-I expression, augments immune response and suppresses cholesterol accumulation. These findings demonstrate that ATG7 inhibition has therapeutic potential and application of statins can increase the sensitivity to immune checkpoint inhibitors.

First-trimester fetal size, accelerated growth in utero, and child neurodevelopment in a cohort study.

BACKGROUND: Early pregnancy is a critical window for neural system programming; however, the association of first-trimester fetal size with children's neurodevelopment remains to be assessed. This study aimed to explore the association between first-trimester fetal size and children's neurodevelopment and to examine whether intrauterine accelerated growth could compensate for the detrimental effects of first-trimester restricted growth on childhood neurodevelopment. METHODS: The participants were from a birth cohort enrolled from March 2014 to March 2019 in Wuhan, China. A total of 2058 fetuses with crown to rump length (CRL) (a proxy of first-trimester fetal size) measurements in the first trimester and neurodevelopmental assessment at age 2 years were included. We measured the first-trimester CRL and defined three fetal growth patterns based on the growth rate of estimated fetal weight from mid to late pregnancy. The neurodevelopment was assessed using the Bayley Scales of Infant Development of China Revision at 2 years. RESULTS: Each unit (a Z score) increase of first-trimester CRL was associated with increased scores in mental developmental index (MDI) (adjusted beta estimate = 1.19, (95% CI: 0.42, 1.95), P = 0.03) and psychomotor developmental index (PDI) (adjusted beta estimate = 1.36, (95% CI: 0.46, 2.26), P < 0.01) at age 2 years, respectively. No significant association was observed between fetal growth rate and PDI. For children with restricted first-trimester fetal size (the lowest tertile of first-trimester CRL), those with "intrauterine accelerated growth" pattern (higher growth rates) had significantly higher MDI (adjusted beta estimate = 6.14, (95% CI: 3.80, 8.49), P < 0.001) but indistinguishable PDI compared to those with "intrauterine faltering growth" pattern (lower growth rates). Main limitations of this study included potential misclassification of gestational age due to recall bias of the last menstrual period and residual confounding. CONCLUSIONS: The current study suggests that restricted first-trimester fetal size is associated with mental and psychomotor developmental delay in childhood. However, in children with restricted first-trimester fetal size, intrauterine accelerated growth was associated with improved mental development but had little effect on psychomotor development. Additional studies are needed to validate the results in diverse populations.

The TET-Sall4-BMP regulatory axis controls craniofacial cartilage development.

Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.

Neuronal and Molecular Mechanisms Underlying Chronic Pain and Depression Comorbidity in the Paraventricular Thalamus.

Patients with chronic pain often develop comorbid depressive symptoms, which makes the pain symptoms more complicated and refractory. However, the underlying mechanisms are poorly known. Here, in a repeated complete Freund's adjuvant (CFA) male mouse model, we reported a specific regulatory role of the paraventricular thalamic nucleus (PVT) glutamatergic neurons, particularly the anterior PVT (PVA) neurons, in mediating chronic pain and depression comorbidity (CDC). Our c-Fos protein staining observed increased PVA neuronal activity in CFA-CDC mice. In wild-type mice, chemogenetic activation of PVA glutamatergic neurons was sufficient to decrease the 50% paw withdrawal thresholds (50% PWTs), while depressive-like behaviors evaluated with immobile time in tail suspension test (TST) and forced swim test (FST) could only be achieved by repeated chemogenetic activation. Chemogenetic inhibition of PVA glutamatergic neurons reversed the decreased 50% PWTs in CFA mice without depressive-like symptoms and the increased TST and FST immobility in CFA-CDC mice. Surprisingly, in CFA-CDC mice, chemogenetically inhibiting PVA glutamatergic neurons failed to reverse the decrease of 50% PWTs, which could be restored by rapid-onset antidepressant S-ketamine. Further behavioral tests in chronic restraint stress mice and CFA pain mice indicated that PVA glutamatergic neuron inhibition and S-ketamine independently alleviate sensory and affective pain. Molecular profiling and pharmacological studies revealed the 5-hydroxytryptamine receptor 1D (Htr1d) in CFA pain-related PVT engram neurons as a potential target for treating CDC. These findings identified novel CDC neuronal and molecular mechanisms in the PVT and provided insight into the complicated pain neuropathology under a comorbid state with depression and related drug development.

Antibiotic-induced ROS-mediated Fur allosterism contributes to Helicobacter pylori resistance by inhibiting arsR activation of mutS and mutY.

The increasing antibiotic resistance of Helicobacter pylori primarily driven by genetic mutations poses a significant clinical challenge. Although previous research has suggested that antibiotics could induce genetic mutations in H. pylori, the molecular mechanisms regulating the antibiotic induction remain unclear. In this study, we applied various techniques (e.g., fluorescence microscopy, flow cytometry, and multifunctional microplate reader) to discover that three different types of antibiotics could induce the intracellular generation of reactive oxygen species (ROS) in H. pylori. It is well known that ROS, a critical factor contributing to bacterial drug resistance, not only induces damage to bacterial genomic DNA but also inhibits the expression of genes associated with DNA damage repair, thereby increasing the mutation rate of bacterial genes and leading to drug resistance. However, further research is needed to explore the molecular mechanisms underlying the ROS inhibition of the expression of DNA damage repair-related genes in H. pylori. In this work, we validated that ROS could trigger an allosteric change in the iron uptake regulatory protein Fur, causing its transition from apo-Fur to holo-Fur, repressing the expression of the regulatory protein ArsR, ultimately causing the down-regulation of key DNA damage repair genes (e.g., mutS and mutY); this cascade increased the genomic DNA mutation rate in H. pylori. This study unveils a novel mechanism of antibiotic-induced resistance in H. pylori, providing crucial insights for the prevention and control of antibiotic resistance in H. pylori.

CDK12 inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in colorectal cancer.

As the world's fourth most deadly cancer, colorectal cancer (CRC) still needed the novel therapeutic drugs and target urgently. Although cyclin-dependent kinase 12 (CDK12) has been shown to be implicated in the malignancy of several types of cancer, its functional role and mechanism in CRC remain largely unknown. Here, we found that suppression of CDK12 inhibited tumor growth in CRC by inducing apoptosis. And CDK12 inhibition triggered autophagy by upregulating autophagy related gene 7 (ATG7) expression. Inhibition of autophagy by ATG7 knockdown and chloroquine (CQ) further decreased cell viability induced by CDK12 inhibition. Further mechanism exploration showed that CDK12 interacted with protein kinase B (AKT) regulated autophagy via AKT/forkhead box O3 (AKT/FOXO3) pathway. FOXO3 transcriptionally upregulated ATG7 expression and autophagy when CDK12 inhibition in CRC. Level of CDK12 and p-FOXO3/FOXO3 ratio were correlated with survival in CRC patients. Moreover, CDK12 inhibition improved the efficacy of anti-programmed cell death 1(PD-1) therapy in CRC murine models by enhancing CD8 + T cells infiltration. Thus, our study founded that CDK12 inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in CRC. We revealed the roles of CDK12/FOXO3/ATG7 in regulating CRC progression, suggesting potential biomarkers and therapeutic target for CRC.

Approaching Standardization: Mechanical Material Testing of Macroscopic Two-Photon Polymerized Specimens.

Two-photon polymerization (2PP) is becoming increasingly established as additive manufacturing technology for microfabrication due to its high-resolution and the feasibility of generating complex parts. Until now, the high resolution of 2PP is also its bottleneck, as it limited throughput and therefore restricted the application to the production of microparts. Thus, mechanical properties of 2PP materials can only be characterized using nonstandardized specialized microtesting methods. Due to recent advances in 2PP technology, it is now possible to produce parts in the size of several millimeters to even centimeters, finally permitting the fabrication of macrosized testing specimens. Besides suitable hardware systems, 2PP materials exhibiting favorable mechanical properties that allow printing of up-scaled parts are strongly demanded. In this work, the up-scalability of three different photopolymers is investigated using a high-throughput 2PP system and low numerical aperture optics. Testing specimens in the cm-range are produced and tested with common or even standardized material testing methods available in conventionally equipped polymer testing labs. Examples of the characterization of mechanical, thermo-mechanical, and fracture properties of 2PP processed materials are shown. Additionally, aspects such as postprocessing and aging are investigated. This lays a foundation for future expansion of the 2PP technology to broader industrial application.

Case Report: Gas in the esophagus, stomach wall and portal vein with congenital hypertrophic pyloric stenosis.

Background: CHPS dramatically affects infant growth and development and can even cause aspiration resulting from esophageal reflux. There is potential danger. CHPS is common, while CHPS with gas in the stomach wall and portal vein is rare. Gas in the stomach wall and portal vein are often the key features of more serious disease. It can be easily mistaken as a serious disease when patients with CHPS have gas in the stomach wall and portal vein. Case presentation: A 56-day-old baby was hospitalized for aspiration pneumonia after vomiting without bile for 20 days. Compared with vomiting, which is the most common symptom, pneumonia tends to attract more attention. Because of pneumonia, a chest CT scan was performed and revealed massive gas accumulation in the walls of the esophagus, stomach, and portal vein. Therefore, NEC was considered first and was treated conservatively for one week. However, the vomiting continued, and CHPS was confirmed by ultrasound. The delay in CHPS diagnosis was due to insufficient recognition of the signs of gas accumulation. Because of inexperience and lack of knowledge about CHPS with gastrointestinal pneumatosis, physicians failed to make an early accurate diagnosis. Case 2 was a 29-day-old male who was admitted to the hospital with vomiting without bile. He was examined by ultrasound, which revealed gas in the stomach wall and portal vein after admission to the hospital. No peritonitis was found after a detailed and comprehensive physical examination. Emergency life-threatening diseases such as NEC were quickly ruled out. He received surgery as soon as possible and had an uneventful recovery with no complications. Conclusion: CHPS may present with gas in the gastric or esophageal wall and portal vein, which is not a contraindication to surgery.

Enhancing Chronic Wound Healing through Engineering Mg2+-Coordinated Asiatic Acid/Bacterial Cellulose Hybrid Hydrogels.

Infectious chronic wounds have gradually become a major clinical problem due to their high prevalence and poor treatment outcomes. The urgent need for wound dressings with immune modulatory, antibacterial, and angiogenic properties has led to the development of innovative solutions. Asiatic acid (AA), derived from herbs, has demonstrated excellent antibacterial, anti-inflammatory, and angiogenic effects, making it a promising candidate for incorporation into hydrogel carriers for wound healing. However, there is currently no available report on AA-based self-assembled hydrogels. Here, a novel hybrid hydrogel dressing consists of interpenetrating polymer networks composed of self-assembled magnesium ion (Mg2+) coordinated asiatic acid (AA-Mg) and bacterial cellulose (BC) is developed to promote infected chronic wound healing. A natural carrier-free self-assembled AA-Mg hydrogel with good injectable and self-healing properties could maintain the sustained release of AA and Mg2+ over an extended period. Notably, the introduction of Mg2+ boosted some pharmacological effects of self-assembled hydrogels due to its excellent anti-inflammatory and angiogenesis. In vitro studies confirmed the exceptional biocompatibility, antibacterial efficacy, and anti-inflammatory potential of the AA-Mg/BC hybrid hydrogel, which also exhibited a commendable mechanical strength. Furthermore, in vivo biological results displayed that the hybrid hydrogel significantly accelerated the wound healing process by boosting dense and organized collagen deposition and the granulation tissue and benefiting revascularization. The introduced self-assembled AA-Mg-based hydrogel offers a promising solution for the effective management of chronic wounds. This universal strategy for the preparation of self-assembled hydrogels modulated with bioactive divalent metal ions is able to excavate more herbal small molecules to construct new self-assembled biomaterials.

Parenting behaviors, inhibitory control, and aggression: Moderation by serotonin receptor 2A haplotypes.

Despite the well-established relationship between parenting and child aggression, the mechanisms by which children incur this risk and whether genetic sources contribute to the heterogeneity in their vulnerability are not entirely clear. This study utilized a longitudinal sample of adolescents (n = 1,047, 50.2% females, Mage = 13.32 ± 0.48 years at Time 1) to examine the effects of positive and negative parenting on aggression, as mediated by inhibitory control and moderated by the serotonin receptor 2A (5-HTR2A) haplotype. Mediation analysis revealed that inhibitory control indirectly mediated the link between both positive and negative parenting and overt aggression but not relational aggression. Further, the indirect effect of negative parenting on overt aggression via inhibitory control was moderated by the 5-HTR2A haplotype. Compared to adolescents carrying zero copies of Thymine-Thymine haplotype, those with one copy of Thymine-Thymine haplotype had better inhibitory control when experiencing less negative parenting, which buffers the risk for overt aggression. However, the mediating role of inhibitory control did not hold in the positive parenting model. These findings elucidate the manner by which adolescents with different genetic predispositions develop aggressive behaviors in the context of family and suggest different etiology of overt and relational aggression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).