A Class of Heptaphyrins with NIR Absorption Modulated by Metal Coordination and Nucleophilic Substitution.

The intensive interest in expanded porphyrins can be attributed to their appealing photoelectric and coordination behavior. In this work, an N-confused heptaphyrin 1 was synthesized by an acid-catalyzed [3+4] condensation reaction. The introduction of an N-confused pyrrolic unit into the heptaphyrin macrocycle led to the formation of a figure-eight-like conformation with nonsymmetrical "NNNN" and "NNNC" coordination cavities employable for bimetallic coordination. As a result, chelation of 1 with Zn(II) and Cu(II) afforded mono-Zn(II) complex 2 and bis-Cu(II) complex 3, respectively, with the metal atoms exhibiting distorted square-planar geometries. In complex 3, an oxygen atom is attached to the α-C atom of N-confused pyrrole D, and thus the N and C atoms of ring D participate in coordination within the two cavities. Interestingly, treatment of 1 with Cs2CO3 in MeOH resulted in regioselective substitution of all the seven para-F atoms in the meso-C6F5 groups as well as the α-H of ring D by eight methoxy moieties. Complex 3 displays a red-shifted absorption band edge of ca. 2200 nm, compared to that of ca. 1600 nm observed for 1. This work provides an example of incorporating an N-confused pyrrole to construct expanded porphyrins with distinctive coordination behavior and tunable NIR absorption.

Alcohol induces p53-mediated apoptosis in neural crest by stimulating the AMPK-mediated suppression of TORC1, p70/S6K, and ribosomal biogenesis.

BACKGROUND: Prenatal alcohol exposure is a leading cause of permanent neurodevelopmental disability. Diagnosis is often initiated by a distinctive craniofacial appearance that originates, in part, from the apoptotic deletion of craniofacial progenitors, a stem cell lineage called the neural crest (NC). We recently demonstrated that alcohol causes nucleolar stress in NC through its suppression of Ribosome Biogenesis (RBG) and this suppression is causative in their p53/MDM2-mediated apoptosis. Here, we show that this nucleolar stress originates from alcohol's activation of AMPK, which suppresses TORC1 and the p70/S6K-mediated stimulation of RBG. METHODS: Alcohol-exposed cells of the pluripotent, primary cranial NC line O9-1 were evaluated with respect to their p70/S6K, TORC1, and AMPK activity. The functional impact of these signals with respect to RBG, p53, and apoptosis were assessed using gain-of-function constructs and small molecule mediators. RESULTS: Alcohol rapidly (<2hr) increased pAMPK, p-Raptor, p-mTOR(S2446), and reduced both total and p-p70/S6K in NC cells. These changes persisted for at least 12hr to 18hr following alcohol exposure. Attenuation of these signals via gain- or loss-of-function approaches prevented alcohol's suppression of rRNA synthesis and the induction of p53-stimulated apoptosis. CONCLUSIONS: We conclude that alcohol induces ribosome dysbiogenesis and activates their p53/MDM2-mediated apoptosis via its activation of pAMPK, which in turn activates Raptor to suppress the TORC1/S6K-mediated promotion of ribosome biogenesis. This represents a novel mechanism underlying alcohol's neurotoxicity and is consistent with findings that TORC1/S6K networks are critical for cranial NC survival.

Prognostic factors for esophageal respiratory fistula in unresectable esophageal squamous cell carcinoma treated with radiotherapy.

Limited studies have focused on the prognostic factors of esophageal respiratory fistula (ERF) associated with radiotherapy in patients with unresectable esophageal squamous cell carcinoma (ESCC). Between January 1st, 2014 and January 1st, 2021, we included patients who were initially diagnosed with unresectable ESCC and underwent radiotherapy. All patients were followed up for a period of 2 years after completing their radiotherapy treatment. The primary outcomes of the study were defined as death or severe adverse events. The survival curves of ERF were calculated using the Kaplan-Meier method. Cox proportional hazards model was employed to calculated the prognostic factors. A cohort of 232 patients underwent radiotherapy, of whom 32 patients experienced ERF. The median period from initial diagnosis of ESCC to ERF was 5.75 months, and the median period from ERF to the primary outcome was 4.6 weeks. Neck + upper chest location (odds ratio [OR] 3.305), high T stage (OR 1.765), esophageal stenosis (OR 1.073), high neutrophil to lymphocyte ratio (NLR) (OR 1.384) and platelet to lymphocyte ratio (PLR) (OR 1.765) were risk factors for the occurrence of ERF. Cox regression analysis suggested that tumor location (hazards ratio [HR] 3.572, 95% confidence interval [CI] 2.467-5.1), high T stage (HR 4.050, 95% CI 2.812-5.831), esophageal stenosis (HR 2.643, 95% CI 1.753-3.983), high PLR (HR 2.541, 95% CI 1.868-3.177) were independent prognostic factors for poor survival. Esophageal stenosis, neck + upper chest tumor location, high T stage and PLR predicted the prognosis of ERF in ESCC patients undergoing radiotherapy.

Safety and feasibility of third-party cytotoxic T lymphocytes for high-risk patients with COVID-19.

ABSTRACT: Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received a single infusion of 1 of 4 escalating doses of a product containing 68.5% SARS-CoV-2-specific CD8+ CTLs/total cells. Symptom improvement and resolution in these patients was compared with an observational group of 18 patients lacking HLA-A∗02:01 who could receive standard of care. No dose-limiting toxicities were observed at any dosing level. Nasal swab polymerase chain reaction testing showed ≥88% and >99% viral elimination from baseline in all patients at 4 and 14 days after infusion, respectively. The CTLs did not interfere with the development of endogenous anti-SARS-CoV-2 humoral or cellular responses. T-cell receptor ß analysis showed persistence of donor-derived SARS-CoV-2-specific CTLs through the end of the 6-month follow-up period. Interventional patients consistently reported symptomatic improvement 2 to 3 days after infusion, whereas improvement was more variable in observational patients. SARS-CoV-2-specific CTLs are a potentially feasible cellular therapy for COVID-19 illness. This trial was registered at www.clinicaltrials.gov as #NCT04765449.

Molecular characterization of SARS-CoV-2 nucleocapsid protein.

Corona Virus Disease 2019 (COVID-19) is a highly prevalent and potent infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until now, the world is still endeavoring to develop new ways to diagnose and treat COVID-19. At present, the clinical prevention and treatment of COVID-19 mainly targets the spike protein on the surface of SRAS-CoV-2. However, with the continuous emergence of SARS-CoV-2 Variants of concern (VOC), targeting the spike protein therapy shows a high degree of limitation. The Nucleocapsid Protein (N protein) of SARS-CoV-2 is highly conserved in virus evolution and is involved in the key process of viral infection and assembly. It is the most expressed viral structural protein after SARS-CoV-2 infection in humans and has high immunogenicity. Therefore, N protein as the key factor of virus infection and replication in basic research and clinical application has great potential research value. This article reviews the research progress on the structure and biological function of SARS-CoV-2 N protein, the diagnosis and drug research of targeting N protein, in order to promote researchers' further understanding of SARS-CoV-2 N protein, and lay a theoretical foundation for the possible outbreak of new and sudden coronavirus infectious diseases in the future.

Dual-channel air-pulse optical coherence elastography for frequency-response analysis.

Microliter air-pulse optical coherence elastography (OCE) has recently been proposed for the characterization of soft-tissue biomechanics using transient, sub-nanometer to micrometer-scale natural frequency oscillations. However, previous studies have not been able to provide real-time air-pulse monitoring during OCE natural frequency measurement, which could lead to inaccurate measurement results due to the unknown excitation spectrum. To address this issue, we introduce a dual-channel air-pulse OCE method, with one channel stimulating the sample and the other being simultaneously measured with a pressure sensor. This allows for more accurate natural frequency characterization using the frequency response function, as proven by a comprehensive comparison under different conditions with a diverse range of excitation spectra (from broad to narrow, clean to noisy) as well as a diverse set of sample response spectra. We also demonstrate the capability of the frequency-response analysis in distinguishing samples with different stiffness levels: the dominant natural frequencies increased with agar concentrations (181-359 Hz, concentrations: 1-2%, and maximum displacements: 0.12-0.47 µm) and intraocular pressures (IOPs) for the silicone cornea (333-412 Hz, IOP: 5-40 mmHg, and maximum displacements: 0.41-0.52 µm) under a 200 Pa stimulation pressure. These frequencies remained consistent across different air-pulse durations (3 ms to 35 ms). The dual-channel OCE approach that uses transient, low-pressure stimulation and high-resolution imaging holds the potential to advance our understanding of sample frequency responses, especially when investigating delicate tissues such as the human cornea in vivo.

Alcohol exposure suppresses ribosome biogenesis and causes nucleolar stress in cranial neural crest cells.

Prenatal alcohol exposure (PAE) causes cognitive impairment and a distinctive craniofacial dysmorphology, due in part to apoptotic losses of the pluripotent cranial neural crest cells (CNCs) that form facial bones and cartilage. We previously reported that PAE rapidly represses expression of >70 ribosomal proteins (padj = 10-E47). Ribosome dysbiogenesis causes nucleolar stress and activates p53-MDM2-mediated apoptosis. Using primary avian CNCs and the murine CNC line O9-1, we tested whether nucleolar stress and p53-MDM2 signaling mediates this apoptosis. We further tested whether haploinsufficiency in genes that govern ribosome biogenesis, using a blocking morpholino approach, synergizes with alcohol to worsen craniofacial outcomes in a zebrafish model. In both avian and murine CNCs, pharmacologically relevant alcohol exposure (20mM, 2hr) causes the dissolution of nucleolar structures and the loss of rRNA synthesis; this nucleolar stress persisted for 18-24hr. This was followed by reduced proliferation, stabilization of nuclear p53, and apoptosis that was prevented by overexpression of MDM2 or dominant-negative p53. In zebrafish embryos, low-dose alcohol or morpholinos directed against ribosomal proteins Rpl5a, Rpl11, and Rps3a, the Tcof homolog Nolc1, or mdm2 separately caused modest craniofacial malformations, whereas these blocking morpholinos synergized with low-dose alcohol to reduce and even eliminate facial elements. Similar results were obtained using a small molecule inhibitor of RNA Polymerase 1, CX5461, whereas p53-blocking morpholinos normalized craniofacial outcomes under high-dose alcohol. Transcriptome analysis affirmed that alcohol suppressed the expression of >150 genes essential for ribosome biogenesis. We conclude that alcohol causes the apoptosis of CNCs, at least in part, by suppressing ribosome biogenesis and invoking a nucleolar stress that initiates their p53-MDM2 mediated apoptosis. We further note that the facial deficits that typify PAE and some ribosomopathies share features including reduced philtrum, upper lip, and epicanthal distance, suggesting the facial deficits of PAE represent, in part, a ribosomopathy.

Structural phase transition and potential superconductivity initiated by pressure-driven in 1T-CrSe2.

The exploration of the superconducting properties of antiferromagnetic parent compounds containing transition metals under pressure provides a unique idea for finding and designing superconducting materials with better performance. In this paper, the close relationship between the possible superconductivity and structure phase transition of the typical van der Waals layered material 1T-CrSe2induced by pressure is studied by means of electrical transport and x-ray diffraction for the first time. We introduce the possibility of pressure-induced superconductivity at 20 GPa, with a criticalTcof approximately at 4 K. The superconductivity persists up to the highest measured pressure of 70 GPa, with a maximumTc∼ 5 K at 24 GPa. We observed a structure phase transition fromP-3m1 toC2/mspace group in the range of 9.4-11.7 GPa. The results show that the structural phase transition leads to the metallization of 1T-CrSe2and the further pressure effect makes the superconductivity appear in the new structure. The material undergoes a transition from a two-dimensional layered structure to a three-dimensional structure under pressure. This is the first time that possible superconductivity has been observed in 1T-CrSe2.

Biomass-derived polymer as a flexible "zincophilic-hydrophobic" solid electrolyte interphase layer to enable practical Zn metal anodes.

Aqueous zinc ion batteries (AZIBs) face significant challenges stemming from Zn dendrite growth and water-contact attack, primarily due to the lack of a well-designed solid electrolyte interphase (SEI) to safeguard the Zn anode. Herein, we report a bio-mass derived polymer of chitin on Zn anode (Zn@chitin) as a novel and robust artificial SEI layer to boost the Zn anode rechargeability. The polymeric chitin SEI layer features both zincophilic and hydrophobic characteristics to target the suppressed dendritic Zn formation as well as the water-induced side reactions, thus harvesting a dendrite-free and corrosion-resistant Zn anode. More importantly, this polymeric interphase layer is strong and flexible accommodating the volume changes during repeated cycling. Based on these benefits, the Zn@chitin anode demonstrates prolonged cycling performance surpassing 1300 h under an ultra-large current density of 20 mA cm-2, and a long cycle life of 680 h with a record-high zinc utilization rate of 80 %. Besides, the assembled Zn@chitin/V2O5 full batteries reveal excellent capacity retention and rate performance under practical conditions, proving the reliability of our proposed strategy for industrial AZIBs. Our research offers valuable insights for constructing high-performance AZIBs, and simultaneously realizes the high-efficient use of cheap biomass from a "waste-to-wealth" concept.

Advancements in lipid-based delivery systems for functional foods: a comprehensive review of literature and patent trends.

Lipid-based delivery systems (LDS) have emerged as cornerstone techniques for bolstering the bioavailability of lipophilic bioactive compounds, addressing challenges related to solubility, stability, and absorption. This critical review examined a substantial dataset of 6,907 scientific articles and 3,021 patents from 2001-2023, elucidating the multifaceted evolution of LDS, with a particular focus on its industrial and patent-driven perspective. Notably, there were pronounced surges in functional food patent applications in 2004, 2011, and 2019. The trajectory revealed a shift from foundational nanoemulsions to more complex structures, such as double/multiple emulsions, solid lipid nanoparticles, Pickering emulsions, and bigels. The review further identified the top 10 leading institutions shaping this domain. Technologies like spray-drying, microfluidics, and phase gelation had revolutionized the landscape, resulting in refined sensory experiences, innovative reduced-fat formulations, enriched beverages, tailor-made infant nutrition, and nuanced release mechanisms for flavors. The review also spotlighted current research frontiers, notably Pickering emulsions, bigels, and multiple emulsions. These emerging technologies not only exemplified the ongoing innovation in the field but also underscored their potential in reshaping the future landscape of value-added functional foods.

CCL20 and CD8A as potential diagnostic biomarkers for HBV-induced liver fibrosis in chronic hepatitis B.

Background: The main cause of the liver fibrosis (LF) remains hepatitis B virus (HBV) infection, especially in China. Histologically, liver fibrosis still occurs progressively in chronic hepatitis B (CHB) patients, even if HBV-DNA is negative or undetectable. The diagnosis of LF is beneficial to control the development of it, also it may promote the reversal of LF. Although liver biopsy is the gold standard of diagnosis in LF at present, it isa traumatic diagnosis. There are no diagnostic biomarkers as yet for the condition. It is badly in need of biomarkers clinically, which is simple to test, minimally invasive, highly specific, and sensitive. Early detection of HBV-LF development is crucial in the prevention, treatment, and prognosis prediction of HBV-LF. Cytokines are closely associated with both immune regulation and inflammation in the progression of hepatitis B virus associated-liver fibrosis (HBV-LF). In this bioinformatic study, we not only analyzed the relationship between HBV-LF and immune infiltration, but also identified key genes to uncover new therapeutic targets. Objectives: To find potential biomarkers for liver fibrosis in the development of chronic hepatic B patients. Materials and methods: We obtained two sets of data including CHB/healthy control and CHB/HBV-LF from the Integrated Gene Expression (GEO) database to select for differential expression analysis. Protein-protein interaction (PPI) network was also generated, while key genes and important gene modules involved in the occurrence and development of HBV-LF were identified. These key genes were analyzed by functional enrichment analysis, module analysis, and survival analysis. Furthermore, the relationship between these two diseases and immune infiltration was explored. Results: Among the identified genes, 150 were individually associated with CHB and healthy control in the differential gene expression (DGE) analysis. While 14 with CHB and HBV-LF. It was also analyzed in the Robust rank aggregation (RRA) analysis, 34 differential genes were further identified by Cytohubba. Among 34 differential genes, two core genes were determined: CCL20 and CD8A. CCL20 was able to predict CHB positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.883, 95% confidence interval [CI] 0.786-0.963), while HBV-LF positivity ([AUC-ROC] = 0.687, 95% confidence interval [CI] 0.592-0.779). And CD8A was able to predict CHB positivity ([AUC-ROC] = 0.960, 95% confidence interval [CI] 0.915-0.992), while HBV-LF positivity ([AUC-ROC] = 0.773, 95% confidence interval [CI] 0.680-0.856). Relationship between CCL20 gene expression and LF grades was P < 0.05, as well as CD8A. Conclusion: CCL20 and CD8A were found to be potential biomarkers and therapeutic targets for HBV-LF. It is instructive for research on the progression of LF in HBV patients, suppression of chronic inflammation, and development of molecularly targeted-therapy for HBV-LF.

Treatment of abdominal pain due to deficiency syndrome of the spleen and stomach with Bian stone plus TCM iontophoresis: A case report.

RATIONALE: Bian stone ironing and rubbing traditional Chinese medicine penetration method is based on the theory of regulating the middle and restoring balance. By using Bian stone to heat, ironing, and rubbing, pushing and rubbing in the epigastric area can regulate the spleen and stomach, restore the normal function of the middle jiao qi movement and the functions of the five organs. Bian stone hot ironing can harmonize stomach qi, nourish qi and assist yang, clear the internal organs and clear turbidity, regulate intestinal qi circulation, and promote qi stagnation. PATIENT CONCERNS: The VAS score for stomach pain is 6 points, and the SAS score is moderate anxiety, which seriously affects sleep and daily life. DIAGNOSES: epigastric pain, spleen, and stomach deficiency cold syndrome. INTERVENTIONS: Easy to digest diet, Western medicine provides famotidine acid inhibiting and protecting gastric mucosa, and mosapride promoting gastrointestinal peristalsis medication treatment; Traditional Chinese Medicine provides oral administration of Huangqi Jianzhong Tang and traditional Chinese medicine techniques such as Bianchi Ironing and Moxibustion for treatment. OUTCOMES: The patient's symptoms of stomach pain have significantly improved, with a decrease in the epigastric pain score to 0, improved anxiety, reduced fatigue, improved sleep, improved epigastric fullness, unobstructed bowel movements, and improved quality of life. The patient is very satisfied. LESSONS: The method of using Bian stone ironing and rubbing traditional Chinese medicine to treat stomach pain caused by the spleen and stomach deficiency cold can alleviate the symptoms of stomach pain in patients, and the improvement of symptoms shows a gradual increase, with significant effects. At the same time, it significantly improves patient anxiety and fatigue symptoms and can increase the sample size in future work to further clarify its clinical effects.

The value of audiovisual sexual stimulation with virtual reality in diagnosing erectile dysfunction.

Background: The traditional audiovisual sexual stimulation (AVSS) test may experience limitations including low erectile response rate and lack of unified diagnostic criteria. Aim: We aimed to explore the clinical value of AVSS with virtual reality (VR-AVSS) test in assessing erectile function and diagnosing erectile dysfunction (ED). Methods: Participants 18 to 60 years of age were screened for analysis in 3 clinical centers from June 2020 to March 2022. Demographic data, 5-item International Index of Erectile Function (IIEF-5), erectile hardness score (EHS), and self-reported symptom questions were collected. The ED patients and control patients were confirmed according to the IIEF-5 and EHS. All subjects watched a 60-minute erotic video by VR device during RigiScan recording. The parameters including tip average rigidity, tip effective erectile duration (duration of rigidity ≥60%, tip effective erectile duration), base average rigidity, and base effective erectile duration were evaluated. Outcomes: The main outcome of interest was the application of VR immersion technology to improve the traditional AVSS test. Results: A total of 301 ED cases and 100 eligible control patients were included for final analysis. Compared with control patients, ED cases had significantly lower IIEF-5 scores, EHS, positive response rate, and erectile rigidity and duration. The positive response rate of ED and control patients were 75.5% and 90.9%, respectively. The cutoff points of tip average rigidity, tip effective erectile duration, base average rigidity, and base effective erectile duration were 40.5% (sensitivity: 77.6%, specificity: 70.2%; P < .001), 4.75 minutes (sensitivity: 75.9%, specificity: 75.4%; P < .001), 48.5% (sensitivity: 77.6%, specificity: 75.1%; P < .001), and 7.75 minutes (sensitivity: 79.3%, specificity: 75.7%; P < .001). Clinical Implications: The technological superiority of VR will enable the VR-AVSS immersion test to be a more accurate detection than traditional AVSS modes. Strengths and Limitations: Our study applied VR immersion technology to establish the standard operation procedure for the AVSS test, which could effectively reduce the interference of adverse factors and minimize the detecting errors. However, the test data only included positive response subjects, so the true erectile status of men with a negative response to the AVSS test cannot be obtained. Conclusions: The VR-AVSS test can effectively improve the diagnostic accuracy of ED. The average rigidity and effective erectile duration were the optimal diagnostic parameters for excluding ED.

Differential Water Conservation Capacity in Broadleaved and Mixed Forest Restoration in Latosol Soil-Eroded Region, Hainan Province, China.

The water conservation capacity of the litter and soil layers of forest ecosystems improves the function of forest ecosystems in conserving soil and water. Plantation restoration plays a key role in preventing soil erosion. In order to evaluate the water conservation capacity of plantation restoration in Latosol soil-eroded region, we analyzed the litter thickness and mass, water absorption process, water holding recovery process, and soil water holding capacity of five restoration types (Hevea brasiliensis, Acacia mangium, Eucalyptus robusta, Acacia-Eucalyptus, and Acacia-Hevea) in the Mahuangling Watershed, Hainan province. The results showed that the thickness of the litter ranged from approximately 3.42 ± 0.24 to 4.73 ± 0.81 cm, and the litter mass ranged from 5.04 ± 1.52 t·ha-1 to 13.16 ± 1.76 t·ha-1, with higher litter mass in the SL layer than in the UL layer. The litter mass of A. mangium was higher than that of H. brasiliensis, E. robusta, Acacia-Eucalyptus, and Acacia-Hevea, which was 3.16 ± 1.76 t·ha-1. A. mangium forest was significantly higher than other plantation restoration types in terms of the maximum water retention capacity (Qmax) and the effective water retention capacity (Qeff). The soil bulk weight ranged from approximately 1.52 ± 0.09 to 1.59 ± 0.08 g·cm-3, and porosity ranged from 31.77 ± 4.72 to 35.62 ± 3.02%, both of which increased with the depth of the soil layer. The water holding capacity of 0-60 cm soil varied from approximately 12.94 ± 7.91 to 45.02 ± 31.79 t·ha-1, with A. mangium having the best soil permeability and the strongest soil water holding capacity. The entropy weight method was used to conduct a comprehensive evaluation, and the results showed that the water conservation capacity of the soil layer was 1.26 times higher than that of the litter layer, in which the water conservation capacity of A. mangium was the strongest, with a comprehensive evaluation value of 0.2854, which effectively intercepted rainfall and reduced surface runoff. Hence, we suggest that the planting of A. mangium should be considered in future ecological restoration projects of the erosion area of Mahuangling in order to improve the function of conserving soil and water in a restoration forest ecosystem.

Alcohol Exposure Induces Nucleolar Stress and Apoptosis in Mouse Neural Stem Cells and Late-Term Fetal Brain.

Prenatal alcohol exposure (PAE) is a leading cause of neurodevelopmental disability through its induction of neuronal growth dysfunction through incompletely understood mechanisms. Ribosome biogenesis regulates cell cycle progression through p53 and the nucleolar cell stress response. Whether those processes are targeted by alcohol is unknown. Pregnant C57BL/6J mice received 3 g alcohol/kg daily at E8.5-E17.5. Transcriptome sequencing was performed on the E17.5 fetal cortex. Additionally, primary neural stem cells (NSCs) were isolated from the E14.5 cerebral cortex and exposed to alcohol to evaluate nucleolar stress and p53/MDM2 signaling. Alcohol suppressed KEGG pathways involving ribosome biogenesis (rRNA synthesis/processing and ribosomal proteins) and genes that are mechanistic in ribosomopathies (Polr1d, Rpl11; Rpl35; Nhp2); this was accompanied by nucleolar dissolution and p53 stabilization. In primary NSCs, alcohol reduced rRNA synthesis, caused nucleolar loss, suppressed proliferation, stabilized nuclear p53, and caused apoptosis that was prevented by dominant-negative p53 and MDM2 overexpression. Alcohol's actions were dose-dependent and rapid, and rRNA synthesis was suppressed between 30 and 60 min following alcohol exposure. The alcohol-mediated deficits in ribosomal protein expression were correlated with fetal brain weight reductions. This is the first report describing that pharmacologically relevant alcohol levels suppress ribosome biogenesis, induce nucleolar stress in neuronal populations, and involve the ribosomal/MDM2/p53 pathway to cause growth arrest and apoptosis. This represents a novel mechanism of alcohol-mediated neuronal damage.

Dietary Supplementation with Bupleuri Radix Reduces Oxidative Stress Occurring during Growth by Regulating Rumen Microbes and Metabolites.

Oxidative stress (OS) in ruminants is closely associated with disease; thus, improving antioxidant capacity is an important strategy for maintaining host health. Bupleuri Radix (BR) could significantly improve host health and stress levels. However, the clear antioxidant mechanism of the function of BR remains unknown. In the current study, LC-MS metabolomics combined with 16S rRNA gene sequencing was employed to explore the effects of BR on rumen microbiota and metabolites in Shanbei Fine-Wool Sheep (SFWS), and Spearman correlation analyses of rumen microbiota, metabolites, and OS were performed to investigate the mechanism of antioxidant function of BR. Our results indicated that as SFWS grows, levels of OS and antioxidant capacity increase dramatically, but providing BR to SFWS enhances antioxidant capacity while decreasing OS. Rumen microbiota and OS are strongly correlated, with total antioxidant capacity (T-AOC) showing a significant negative correlation with Succiniclasticum and a positive correlation with Ruminococcus. Importantly, the Chao1 index was significantly negatively correlated with malondialdehyde (MDA) and positively correlated with superoxide dismutase (SOD) and T-AOC. Two biomarkers connected to the antioxidant effects of BR, 5,6-DHET and LPA (a-25:0/0:0), were screened according to the results of metabolomics and Spearman analysis of rumen contents, and a significant relationship between the concentration of rumen metabolites and OS was found. Five metabolic pathways, including glycerolipid, glutathione, nucleotide, D-amino acid, and inositol phosphate metabolism, may have a role in OS. The integrated results indicate that rumen microbiota and metabolites are strongly related to OS and that BR is responsible for reducing OS and improving antioxidant capacity in post-weaned SFWS. These findings provide new strategies to reduce OS occurring during SFWS growth.

Perioperative care of neonates with critical pulmonary stenosis: Case report.

RATIONALE: Summarizing the perioperative nursing experience in the successful treatment of 4 neonates with critical pulmonary stenosis (CPS). PATIENT CONCERNS: Of the 4 patients, 3 had postnatal shortness of breath and varying degrees of cyanosis, aggravated by crying and noise, and 1 had no obvious shortness of breath and cyanosis. The preoperative auscultation of the precordial region could be heard 3-4/6 systolic murmur; echocardiography was diagnosed as CPS, combined with patent ductus arteriosus, right ventricular dysplasia, and severe tricuspid regurgitation. Four children were treated with prostaglandin 5 ng/(kg-min) to maintain a certain degree of pulmonary blood flow to improve hypoxemia, effectively preventing ductus arteriosus from closure, and the infusion was discontinued 2 hours prior to the operation. Three of the children required ventilator-assisted respiration to relieve severe hypoxia and correct acidosis before surgery. DIAGNOSIS: Neonatal CPS was diagnosed. INTERVENTIONS: Four neonates with rapidly developing conditions were admitted to the hospital, a multidisciplinary in-hospital consultation was organized immediately, and a multidisciplinary collaborative team was set up, consisting of medical doctors and nurses from the medical department, the neonatal intensive care unit, cardiovascular medicine, cardiac ultrasound room, anesthesiology department, and radiology and interventional medicine department. The multidisciplinary team evaluated the treatment modality of the children and finally decided to perform percutaneous balloon pulmonary valvuloplasty. The surgical team included specialists from the Department of Cardiovascular Medicine, Department of Interventional Radiology, Cardiac Ultrasound Unit, and Department of Anesthesiology. OUTCOMES: All 4 neonates were successfully operated and discharged from the hospital. Multidisciplinary follow-up interventions were carried out 1 year after discharge, and the children were in good condition. LESSONS: The specialty nursing-led multidisciplinary collaboration model significantly improves the professional competence of nurses from various specialties, promotes the integration and development of multispecialty disciplines, and provides better quality services for children, which is the key to improving the success rate of percutaneous balloon pulmonary valvuloplasty in neonates.

MR Diffusion-Weighted Imaging in Evaluating Immediate HIFU Treatment Response of Uterine Fibroids.

BACKGROUND: Nowadays, High Intensity Focused Ultrasound (HIFU) is a common surgery option for the treatment of uterine fibroids in China, the immediate response of which is clinically evaluated using Contrast Enhanced (CE) imaging. However, the injection of gadolinium with its potential adverse effect is of concern in CE and therefore, it deserves efforts to find a better imaging method without the need for contrast agent injection for this task. OBJECTIVE: To assess the role of diffusion-weighted imaging (DWI) in evaluating the immediate therapeutic response of HIFU treatment for uterine fibroids in comparison with CE. METHODS: 68 patients with 74 uterine fibroids receiving HIFU treatment were enrolled, and immediate treatment response was assessed using post-surgical DWI images. Semi-quantitative ordinal ablation quality grading and quantitative nonperfusion volume (NPV) measurement based on DWI and CE imaging were determined by two experienced radiologists. Agreement of ablation quality grading between DWI and CE was assessed using the weighted kappa coefficient, while intraobserver, interobserver and interprotocol agreements of NPV measurements within and between DWI and CE were evaluated using the intraclass correlation (ICC) and Bland-Altman analysis. RESULTS: Grading of immediate HIFU treatment response showed a moderate agreement between DWI and CE (weighted kappa = 0.446, p < 0.001). NPV measured in 65 fibroids with DWI of Grade 3~5 showed very high ICCs for the intraobserver and interobserver agreement within DWI and CE (all ICC > 0.980, p < 0.001) and also for the interprotocol agreement between DWI and CE (ICC = 0.976, p < 0.001). CONCLUSION: DWI could provide satisfactory ablation quality grading, and reliable NPV quantification results to assess immediate therapeutic responses of HIFU treatment for uterine fibroids in most cases, which suggests that non-contrast enhanced DWI might be potentially used as a more costeffective and convenient method in a large proportion of patients for this task replacing CE imaging.