Endoscopic variceal ligation combined with sclerotherapy for management of gastroesophageal variceal bleeding in pediatric patients: a single-center retrospective study.

Objectives: Portal hypertension (PH) frequently gives rise to severe and life-threatening complications, including hemorrhage accompanied by the rupture of esophageal and gastric varices. In contrast to the guidelines for the management of PH in adults, the optimal endoscopic management of variceal bleeding for secondary prophylaxis in children remains unclear. The present study evaluated the efficacy and safety of endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST) to control gastroesophageal variceal bleeding in children. Methods: This retrospective study included children with gastroesophageal variceal bleeding who underwent EST or EVL at Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between February 2013 and March 2020. Short-term hemostasis rate and long-term rebleeding rate were evaluated. Adverse events related to the procedures, such as esophageal ulcer, esophageal stricture, abnormal embolization, pneumonia and perforation, were also recorded. Results: EVL (n = 8) and EST (n = 13) were performed successfully in all pediatric patients diagnosed with moderate to severe esophageal varices concurrent with gastric varices. Hemostasis was achieved during episodes of upper gastrointestinal bleeding. The mean volume of each single aliquot of cyanoacrylate injected was 0.3 ± 0.1 ml (range: 0.1-0.5 ml). Varices were eradicated in six (75%) of the eight patients who underwent EVL after a median 2 (range: 1-4) procedures and a median time of 3.40 months (range: 1.10-13.33 months). Eleven (52.4%) of the 21 patients developed rebleeding events, with the mean duration of hemostasis being 11.1 ± 11.6 months (range 1.0-39.2 months). No treatment-related complications, for example, distal embolism, occurred except for abdominal pain in one patient (4.8%). Conclusions: EST, alone or in combination with EVL, is an effective and safe method of managing gastroesophageal variceal hemorrhage in children undergoing secondary prophylaxis.

Correlation between circulating advanced glycation end products and thioredoxin-interacting protein levels and renal fat content in type 2 diabetes mellitus patients.

BACKGROUND: This study sought to explore the clinical relevance of the associations of serum levels of advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), and thioredoxin-interacting protein (TXNIP) with the renal fat fraction (RFF) in individuals with type 2 diabetes mellitus (T2DM). METHODS: A total of 133 patients with T2DM were enrolled in the study. RFF, which represents the renal fat level, was determined utilizing Dixon magnetic resonance imaging (MRI). Serum levels of AGEs, sRAGE, TXNIP, and other biochemical parameters were measured in patients who fasted. RESULTS: RFF in T2DM patients was positively correlated with the fasting levels of C-peptide (CP), triglycerides (TG), AGEs, TXNIP, and sRAGE (P < 0.05) and negatively correlated with the high-density lipoprotein cholesterol (HDL-c) level (P < 0.05). Pearson's correlation analysis indicated that the serum levels of AGEs, sRAGE, and TXNIP were interrelated and positively correlated (P < 0.05). Then, all patients were assigned to four groups according to the RFF quartile. The HC, CP, TG, AGEs, sRAGE, TXNIP, and DKD percentages tended to increase as the RFF quartiles increased, while the HDL-c level tended to decrease (p for trend < 0.05). Next, multiple linear regression analysis was performed using RFF as the dependent variable. After controlling for covariates related to RFF, the results showed that the serum levels of AGEs and TXNIP were still significantly correlated with RFF. CONCLUSION: These results suggest that circulating AGEs and TXNIP levels may be associated with ectopic fat accumulation in the kidneys of T2DM patients and may serve as indicators of the severity of renal fat deposition.

First-principles Study of Phase-dependent Carrier Transport Mechanism for MASnI3 Sn-based Halide Perovskite.

Organic-inorganic hybrid perovskites have attracted tremendous attentions owing to their excellent properties as next-generation photovoltaic devices. With soft covalent framework, organic-inorganic hybrid perovskites exhibit different phases at different temperatures. The band-edge features of perovskites are mainly contributed by inorganic framework, which means the structural differences between these phases would lead to complex carrier transport. We investigated the carrier transport of Sn-based organic-inorganic hybrid perovskite CH3NH3SnI3 (MASnI3), considering acoustic deformation potential scattering, ionized impurity scattering, and polar optical phonon scattering. It is found that the electron mobility of each phase of MASnI3 is strongly correlated with the Sn-I-Sn bond angle and there is in-plane/out-of-plane anisotropy. The pCOHP (projected crystal orbital Hamilton population) analysis suggested that the tilt and rotation of the [SnI6]4- octahedron influence the Sn(p)-I(p) orbital electron coupling and the electron transport, leading to different band-edge features in multiple phases. The carrier mobility with respect to temperature was further calculated for each phase of MASnI3 in respective temperature intervals, showing lower carrier mobility in high temperature. Comparing the contribution of different scattering mechanisms, it was found that the dominant scattering mechanism is polar optical phonon scattering, while multiple scattering mechanisms compete in individual cases.

A Tunable Threshold Colorimetric DNA Logic Gate for Intuitive Assessment of Chemical Contaminant Exceedance.

Current molecular logic gates are predominantly focused on the qualitative assessment of target presence, which has certain limitations in scenarios requiring quantitative assessment, such as chemical contaminant monitoring. To bridge this gap, we have developed a novel DNA logic gate featuring a tunable threshold, specifically tailored to the limits of contaminants. At the core of this logic gate is a DNA-gold nanoparticle (AuNP) hybrid film that incorporates aptamer sequences to selectively bind to acetamiprid (ACE) and atrazine (ATR). Upon interaction with these contaminants, the film degrades, releasing AuNPs that, in the presence of Hg2+, catalyze the oxidation of TMB, resulting in a visible blue coloration on test paper. This aptamer-enabled process effectively establishes an OR logic gate, with ACE and ATR as inputs and the appearance of blue color as the output. A key innovation of our system is its tunable input threshold. By adjusting the concentration of Hg2+, we can fine-tune the color mutation points to match the input threshold to predefined limits, such as Maximum Residue Limits (MRLs). This alignment allows semiquantitative assessment of contaminant levels, providing intuitive visual feedback of contaminant exceedance. Validation experiments with spiked samples confirm its accuracy and reliability by closely matching HPLC results. Therefore, our colorimetric DNA logic gate is emerging as a promising tool for easy and semiquantitative monitoring of chemical contaminants across diverse applications.

Ultrasonic-assisted nanofiltration separation recovering salvianolic acid B from ethanol wastewater.

The transformation of salvianolic acid B brought on by heat treatment recovery of ethanol eluent, which is a difficult problem in pharmaceutical technology, affects the purity of raw material when the medicinal raw material salvianolic acid B is purified by resin. Ultrasonic-assisted nanofiltration separation (UANS) was first employed to improve efficiency of resource utilization by regulating rejection and separating salvianolic acid B and rosmarinic acid from organic pharmaceutical wastewater. The rejection was related to three variables: ultrasonic power, pH, and ethanol concentration. But there were differences in the effects of variables on the rejections of salvianolic acid B and rosmarinic acid. The rejections of rosmarinic acid and salvianolic acid B showed a decreasing trend with an increase in ultrasonic power or a decrease in pH; however, when the concentration of ethanol was increased from 5 % to 35 %, the salvianolic acid B rejection increased from 84.96 % to 96.60 % and the rosmarinic acid rejection decreased from 35.09 % to 17.51 %. On the basis of response surface methodology (RSM), the optimal UANS parameters for solution conditions involving different ethanol concentrations are as follows: 10 % ethanol solution (ultrasonic power 500 W and pH 6.15), 20 % ethanol solution (ultrasonic power 500 W and pH 6.54), and 30 % ethanol solution (ultrasonic power 460 W and pH 6.34). The molecular proportions of salvianolic acid B were 10.75 %, 7.13 %, and 8.27 % in 10 %, 20 %, and 30 % ethanol wastewater, while the molecular proportions of rosmarinic acid were 40.52 %, 33.83 %, and 69.87 %, respectively. And the recoveries of salvianolic acid B in 10 %, 20 %, and 30 % ethanol wastewater were 93.56 %, 95.04 %, and 97.30 %, respectively, while the recoveries of rosmarinic acid were 3.19 %, 2.27 %, and 0.56 %. The molecular proportion and the rejection are correlated exponentially. In comparison with conventional nanofiltration separation (CNS), UANS is able to resolve the conflict between rosmarinic acid and salvianolic acid B in pharmaceutical wastewater, as well as enhance resource recycling and separation efficiency to prevent pollution of the environment from pharmaceutical wastewater. Experiments using UANS at different power intensities suggest that the ultrasonic at a power intensity of 46-50 W/L and the power density of 0.92-1.00 W/cm2 may resolve the separation conflict between rosmarinic acid and salvianolic acid B. This work suggests that UANS may be a significant advancement in the field of ultrasonic separation and has several potential uses in the water treatment industry.

Enhanced detection of acetamiprid via a gold nanoparticle-based colorimetric aptasensor integrated with a hybridization chain reaction.

This study presents a novel colorimetric aptasensor, which seamlessly integrates gold nanoparticles (AuNPs) with the amplification potential of the hybridization chain reaction (HCR) for enhanced detection of acetamiprid. The aptamer, hybridized with a partially complementary strand that is covalently linked to AuNPs, serves as the recognition element for acetamiprid. The free end sequence of the aptamer, distal from the AuNP surface, functions as the initiating strand for the HCR, triggering the amplification process. In the absence of acetamiprid, the HCR efficiently occurs, conferring robust salt tolerance to the AuNPs and maintaining their characteristic red coloration. However, in the presence of acetamiprid, the aptamer preferentially binds to its target, disrupting the double-stranded structure and leading to the dissociation of the aptamer from the AuNPs. This dissociation results in a decrease in the HCR product, subsequently diminishing the salt tolerance of AuNPs and triggering a colorimetric transition from red to gray. This integration enhances sensitivity to 3.14 nM. Additionally, carbon quantum dots (CQDs) transduce colorimetric signals to fluorescent ones, further boosting the sensitivity to 0.24 nM. The aptasensor exhibits excellent selectivity and robustness. Real-world testing on tomato, peach, and lettuce shows recoveries of 98.50% to 100.36% with low standard deviations, validating its utility for pesticide residue analysis and food safety. This study provides a powerful tool for rapid and accurate pesticide detection, crucial for food safety.

Unveiling the Pharmacological Mechanisms of Davidiin's Anti-Diabetic Efficacy in Streptozotocin-Treated Rats: A Comprehensive Analysis of Serum Metabolome.

Background: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties. Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS. Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins. Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin's action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.

Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Cancer cells exhibit heterogenous metastatic potential, and high metastatic subclones can enhance metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogenous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration and invasion of CRA cells. Interestingly, high metastatic CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit NF1, thereby activate the RAS-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided the evidence that colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Autophagy regulates bone loss via the RANKL/RANK/OPG axis in an experimental rat apical periodontitis model.

AIM: Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model. METHODOLOGY: Twenty-four female Sprague-Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3-methyladenine (An autophagy inhibitor, 3-MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3-MA group received intraperitoneal injections of saline and 3-MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro-CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one-way analysis of variance (p < .05). RESULTS: Micro-CT showed greater bone loss in the EAP + 3-MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p < .05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3-MA groups. Compared with EAP + saline group, the EAP + 3-MA group showed weaker expression of LC3B (p < .01) and OPG (p < .05), more intense expression of RANK (p < .01) and RANKL (p < .01), and a higher RANKL/OPG ratio (p < .05). CONCLUSION: Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss.

The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway.

Insect wing development is a fascinating and intricate process that involves the regulation of wing size through cell proliferation and apoptosis. In this study, we find that Ter94, an AAA-ATPase, is essential for proper wing size dependently on its ATPase activity. Loss of Ter94 enables the suppression of Hippo target genes. When Ter94 is depleted, it results in reduced wing size and increased apoptosis, which can be rescued by inhibiting the Hippo pathway. Biochemical experiments reveal that Ter94 reciprocally binds to Mer, a critical upstream component of the Hippo pathway, and disrupts its interaction with Ex and Kib. This disruption prevents the formation of the Ex-Mer-Kib complex, ultimately leading to the inactivation of the Hippo pathway and promoting proper wing development. Finally, we show that hVCP, the human homolog of Ter94, is able to substitute for Ter94 in modulating Drosophila wing size, underscoring their functional conservation. In conclusion, Ter94 plays a positive role in regulating wing size by interfering with the Ex-Mer-Kib complex, which results in the suppression of the Hippo pathway.

Application of personalized templates in minimally invasive management of coronal dens invaginatus: a report of two cases.

BACKGROUND: Treating the coronal dens invaginatus (CDI) with pulp infection commonly involves the removal of invagination, which increases the risk of perforation and fracture, and compromises the tooth structure. Minimally invasive endodontic management of CDI is highly recommended. This report describes two cases of type II CDI with the application of personalized templates. CASE PRESENTATION: Two cases of type II CDI, affecting the main root canal in a maxillary canine and a lateral incisor, were diagnosed. A guided endodontics (GE) approach was applied. Cone-beam computed tomography and intraoral scans were imported and aligned in a virtual planning software to design debridement routes and templates. The MICRO principle (which involves the aspects of Mechanical (M) debridement, Irrigation (I), Access cavities (C), Rectilinear routes (R), and Obstruction (O)) was proposed for designing optimal debridement routes for future applications. The templates were innovatively personalized and designed to preserve the tooth structure maximally while effectively debriding the root canal. Root canal treatment with supplementary disinfection was then performed. The follow-up of the two patients revealed favorable clinical and radiographic outcomes. CONCLUSIONS: The GE approach could be a feasible method for preserving healthy dental structure while effectively debriding the root canal, thereby achieving successful and minimally invasive endodontic treatment for CDI.

Ozonated Hydrotherapy Combined with LED Yellow Light Irradiation and Oral Minocycline Treatment for Mild to Moderate Papulopustular Rosacea: A Comparative Retrospective Study.

Objective and Design: The treatment of recurrent rosacea has always been a problem. Oral minocycline has been widely used in the treatment of rosacea. However, the efficacy and safety of ozonated hydrotherapy combined with LED yellow light irradiation and oral minocycline for mild to moderate papulopustular rosacea (PPR) has not been thoroughly studied. Methods: Patients with rosacea who met the criteria and had complete clinical statistic admitted to our hospital from April 2021 to September 2022 were retrospectively collected and divided into combined therapy group and oral only group. The patients in the two groups were treated with minocycline for 8 weeks. In addition, the patients in combined therapy group were treated with ozone hydrotherapy once a week, followed by LED yellow light irradiation for a total of 4 weeks. The Investigator' s global assessment (IGA) score was used to assess the condition. The efficacy was evaluated using the patients' subjective symptom scores. Skin lesion images and adverse reactions were recorded. The recurrence rate was observed after 24 weeks of follow-up. Results: A total of 39 patients included in the study. After 4 weeks of treatment, the effective rate was 90% in combined therapy group and 52.63% in oral only group (p<0.05). After 8 weeks of treatment, the total score of the patients' subjective symptom scores and the scores of itching and burning sensation in combined therapy group were lower than those in oral only group (p<0.05). After 24 weeks of follow-up, the recurrence rate of combined therapy group was 5%, and that of oral only group was 26.32%. The mild adverse reactions experienced by both groups disappeared during follow-up. Conclusion: This combination therapy has a significant, rapid and safe therapeutic effect, especially in relieving itching and burning sensations, and may reduce the recurrence rate.

Fire needle pretreatment with 5-aminolevulinic acid photodynamic therapy combined with low-dose isotretinoin in the treatment of severe refractory nodulocystic acne.

BACKGROUND: Nodulocystic acne is a severe form of acne, which is commonly treated with oral isotretinoin, hormones, or antibiotics. However, drug therapy often has some side effects and poor compliance. Fire needle combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a simple, effective, short-term treatment with few adverse reactions, which is expected to be an effective physiotherapy for nodulocystic acne. Moreover, the combination with isotretinoin can reduce the dosage of the drug, thereby reducing the side effects of isotretinoin. OBJECTIVES: To evaluate the safety and efficacy of fire-needle pretreated ALA-PDT combined with low-dose isotretinoin in the treatment of severe refractory nodulocystic acne. METHODS: This study reported 10 patients with refractory nodulocystic acne who received combined treatment. During the treatment period, all patients received a low dose of oral isotretinoin capsules daily. The acne lesions were pretreated with fire needle before ALA-PDT treatment. The number of acne lesions, including papules, pustules, and nodular cysts, was documented at weeks 0, 2, 4, 8, and 12 to assess the therapeutic efficacy. Concurrently, adverse reactions such as pain, pruritus, and pigmentation changes were recorded and evaluated throughout the treatment course. RESULTS: After combined treatment, all patients achieved good therapeutic effects, with an overall effective rate of 90 % at week 12. After treatment, skin lesions such as nodules, and cysts subsided significantly. The combination therapy has no serious adverse effects and has a favorable safety profile. CONCLUSION: Fire needle pretreatment ALA-PDT combined with low-dose isotretinoin is effective and safe in the treatment of severe refractory nodular cystic acne, which is worthy of clinical promotion and research.

Dermatology Consultation in the Geriatrics Department of a Tertiary Hospital in China: A Retrospective Study of 178 Patients.

Objective: Dermatological consultation plays an important role in diagnosing and treating skin diseases in the Department of Geriatrics. The objective of this study is to provide an analysis of the factors leading geriatric inpatients to seek dermatological consultation, aiming to facilitate accurate diagnosis and effective treatment of skin diseases by healthcare professionals specializing in geriatrics and dermatology. Methods: The electronic health records of hospitalized patients in the Department of Geriatrics who applied for dermatological consultation at the Second Hospital of Shandong University from June 1, 2022, to June 1, 2023, were retrieved. Sex, age, number of consultations, reason for dermatology consultation, and final diagnosis by dermatologists were reviewed. Results: A total of 216 consultations of 178 patients (n=178, 95 men and 83 women) were collected in this study, of whom 153 (86.0%) required only one consultation, 19 (10.7%) required two consultations, and 4 (2.2%) required three consultations. The reasons for dermatology consultations were divided into three categories: the first was for the definitive diagnosis of a new skin condition that developed during the patient's hospitalization (n=165, 76.4%), the second was for the follow-up of the condition and adjustment of medication (n=40, 18.5%), and the third was for the evaluation of the patient's disease that existed before admission to the hospital (n=11, 5.1%). In 165 consultations, most of these diseases (n=131, 79.4%) can be diagnosed by patients' conscious symptoms and clinical manifestations. Some of them need to be diagnosed or differentially diagnosed with the help of supplementary examinations, such as microscopic examination of scabies or fungi, and pathological examination. Conclusion: This study summarized the reasons for dermatology consultations for geriatric inpatients and found that dermatitis/eczema and infectious diseases were the common types of diseases consulted. The findings of this study contribute to the enhanced comprehension and management of dermatological conditions in hospitalized patients by geriatricians, as well as facilitating more efficient diagnosis and treatment by dermatologists.

Surgical Myectomy and Myotomy for Refractory Blepharospasm in Meige Syndrome Patients: A Case Report.

Meige syndrome is a rare neurological disease characterized by segmental dystonia, specifically blepharospasm and oromandibular dystonia. These symptoms are often accompanied by complex movements of the eyelids, lower facial muscles, mandible, and neck muscles. Bilateral blepharospasm is the most common feature of this disease. In this case report, we present the successful treatment of refractory blepharospasm in a 72-year-old woman with Meige syndrome via 2 incisions resulting from myectomy and in situ surgery.

Feasibility and impact of three-dimensional (3D) printing technology in simulated teaching of congenital malformations.

AIMS: This study aimed to investigate the feasibility and effectiveness of utilizing three-dimensional (3D) printing technology in the simulation teaching of congenital malformations. METHODS: We conducted a comparative analysis between an experimental group that received traditional teaching supplemented with 3D printing model demonstrations and hands-on model operation, and a control group that received traditional teaching methods. Various parameters, including classroom interest, classroom interaction, learning enthusiasm, disease awareness, teaching satisfaction, and independent operation confidence, were assessed, along with theoretical and practical tests. RESULTS: The results showed no significant difference in theoretical test scores between the two groups (91.92 ± 15.04 vs. 89.44 ± 14.89), but the practical test revealed a significantly higher number of qualified trainees in the experimental group compared to the control group (23 vs. 8). In terms of classroom engagement, both groups exhibited similar levels of interest (8.08 ± 1.52 vs. 8.74 ± 0.984), classroom interaction (7.88 ± 1.97 vs. 8.7 ± 1.33), learning enthusiasm (8.81 ± 1.021 vs. 8.52 ± 1.189), and disease awareness (8.58 ± 0.99 vs. 8.58 ± 0.99). However, the experimental group demonstrated significantly higher teaching satisfaction (8.81 ± 1.06 vs. 9.19 ± 0.96) and greater operation confidence (7.67 ± 2.56 vs. 5.5 ± 2.79) than the control group. CONCLUSION: 3D printing technology can be effectively utilized to create surgical teaching models, enhancing the confidence of standardized training doctors and improving teaching outcomes.

Neuroinflammation Plays a Potential Role in the Medulla Oblongata After Moderate Traumatic Brain Injury in Mice as Revealed by Nontargeted Metabonomics Analysis.

Moderate traumatic brain injury (mTBI) involves a series of complex pathophysiological processes in not only the area in direct contact with mechanical violence but also in other brain regions far from the injury site, which may be important factors influencing subsequent neurological dysfunction or death. The medulla oblongata (MO) is a key area for the maintenance of basic respiratory and circulatory functions, whereas the pathophysiological processes after mTBI have rarely drawn the attention of researchers. In this study, we established a closed-head cortical contusion injury model, identified 6 different time points that covered the acute, subacute, and chronic phases, and then used nontargeted metabolomics to identify and analyze the changes in differential metabolites (DMs) and metabolic pathways in the MO region. Our results showed that the metabolic profile of the MO region underwent specific changes over time: harmaline, riboflavin, and dephospho-coenzyme A were identified as the key DMs and play important roles in reducing inflammation, enhancing antioxidation, and maintaining homeostasis. Choline and glycerophospholipid metabolism was identified as the key pathway related to the changes in MO metabolism at different phases. In addition, we confirmed increases in the levels of inflammatory factors and the activation of astrocytes and microglia by Western blot and immunofluorescence staining, and these findings were consistent with the nontargeted metabolomic results. These findings suggest that neuroinflammation plays a central role in MO neuropathology after mTBI and provide new insights into the complex pathophysiologic mechanisms involved after mTBI.

Efficient biosynthesis of transglutaminase in Streptomyces mobaraensis via systematic engineering strategies.

Transglutaminases (TGases) have been widely used in food, pharmaceutical, biotechnology, and other industries because of their ability to catalyze deamidation, acyl transfer, and crosslinking reactions between Ƴ-carboxamide groups of peptides or protein-bound glutamine and the Ɛ-amino group of lysine. In this study, we demonstrated an efficient systematic engineering strategy to enhance the synthesis of TGase in a recombinant Streptomyces mobaraensis smL2020 strain in a 1000-L fermentor. Briefly, the enzymatic properties of the TGase TGL2020 from S. mobaraensis smL2020 and TGase TGLD from S. mobaraensis smLD were compared to obtain the TGase TGLD with perfected characteristics for heterologous expression in a recombinant S. mobaraensis smL2020ΔTG without the gene tgL 2020. Through multiple engineering strategies, including promoter engineering, optimizing the signal peptides and recombination sites, and increasing copies of the expression cassettes, the final TGLD activity in the recombinant S. mobaraensis smL2020ΔTG: (PL2020-spL2020-protgLD-tgLD)2 (tgL2020and BT1) reached 56.43 U/mL and 63.18 U/mL in shake flask and 1000-L fermentor, respectively, which was the highest reported to date. With the improvement of expression level, the application scope of TGLD in the food industry will continue to expand. Moreover, the genetic stability of the recombinant strain maintained at more than 20 generations. These findings proved the feasibility of multiple systematic engineering strategies in synthetic biology and provided an emerging solution to improve biosynthesis of industrial enzymes.

Large-Area Flexible Carbon Nanofilms with Synergistically Enhanced Transmittance and Conductivity Prepared by Reorganizing Single-Walled Carbon Nanotube Networks.

Large-area flexible transparent conductive films (TCFs) are highly desired for future electronic devices. Nanocarbon TCFs are one of the most promising candidates, but some of their properties are mutually restricted. Here, a novel carbon nanotube network reorganization (CNNR) strategy, that is, the facet-driven CNNR (FD-CNNR) technique, is presented to overcome this intractable contradiction. The FD-CNNR technique introduces an interaction between single-walled carbon nanotube (SWNT) and Cu─-O. Based on the unique FD-CNNR mechanism, large-area flexible reorganized carbon nanofilms (RNC-TCFs) are designed and fabricated with A3-size and even meter-length, including reorganized SWNT (RSWNT) films and graphene and RSWNT (G-RSWNT) hybrid films. Synergistic improvement in strength, transmittance, and conductivity of flexible RNC-TCFs is achieved. The G-RSWNT TCF shows sheet resistance as low as 69 Ω sq-1 at 86% transmittance, FOM value of 35, and Young's modulus of ≈45 MPa. The high strength enables RNC-TCFs to be freestanding on water and easily transferred to any target substrate without contamination. A4-size flexible smart window is fabricated, which manifests controllable dimming and fog removal. The FD-CNNR technique can be extended to large-area or even large-scale fabrication of TCFs and can provide new insights into the design of TCFs and other functional films.

Neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable hepatocellular carcinoma: the Notable-HCC phase 1b trial.

Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.