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Abstract Glioma is the most common malignant tumor of the central nervous system, with EZH2 playing a crucial regulatory role. This study further explores the abnormal expression of EZH2 and its mechanisms in regulating glioma progression. Additionally, it was found that IHMT-337 can potentially be a therapeutic agent for glioma. The prognosis, expression, and localization of EZH2 were determined using bioinformatics, IHC staining, Western blot (WB) analysis, and immunofluorescence (IF) localization. The effects of EZH2 on cell function were assessed using CCK-8 assays, Transwell assays, and wound healing assays. Public databases and RT-qPCR were utilized to identify downstream targets. The mechanisms regulating these downstream targets were elucidated using MS-PCR and WB analysis. The efficacy of IHMT-337 was demonstrated through IC50 measurements, WB analysis, and RT-qPCR. The effects of IHMT-337 on glioma cells in vitro were evaluated using Transwell assays, EdU incorporation assays, and flow cytometry. The potential of IHMT-337 as a treatment for glioma was assessed using a blood–brain barrier (BBB) model and an orthotopic glioma model. Our research confirms significantly elevated EZH2 expression in gliomas, correlating with patient prognosis. EZH2 facilitates glioma proliferation, migration, and invasion alongside promoting SLC12A5 DNA methylation. By regulating SLC12A5 expression, EZH2 activates the WNK1-OSR1-NKCC1 pathway, enhancing its interaction with ERM to promote glioma migration. IHMT-337 targets EZH2 in vitro to inhibit WNK1 activation, thereby suppressing glioma cell migration. Additionally, it inhibits cell proliferation and arrests the cell cycle. IHMT-337 has the potential to cross the BBB and has successfully inhibited glioma progression in vivo. This study expands our understanding of the EZH2-SLC12A5 axis in gliomas, laying a new foundation for the clinical translation of IHMT-337 and offering new insights for precision glioma therapy.

Abstract Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

BackgroundThere is a crosstalk between gut microbiota and radiotherapy. The aim of this study is to use bibliometric analysis to explore the research status and development trends of research on gut microbiota and radiotherapy.MethodsA literature search regarding publications on gut microbiota and radiotherapy from 2004 to 2023 was retrieved. CiteSpace and VOSviewer were used to conduct the bibliometric analysis. The growth rate of publications, leading countries and institutions, preferred journals, top authors and co-cited authors, top co-cited references, keywords and citation were analyzed in this study.ResultsA total of 2821 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2017. The USA and China had the most publications and made great contributions to this field. The Chinese Academy of Sciences stood out as the institution with the highest number of publications, followed by the Chinese Academy of Medical Sciences & Peking Union Medical College. The most influential authors were Fan Saijun and Li Yuan. PLoS One had the most publications and the most total citations. Highly cited papers and high-frequency keywords illustrated the current status and trends. Furthermore, analysis of keyword with burst revealed that immunotherapy, acid, intestinal barrier, therapy, immunotherapy, fecal microbiota transplantation, etc, are at the forefront of research in this area.ConclusionThis study provides an overview of research on gut microbiota and radiotherapy, highlighting influential contributors, impactful publications, and emerging trends. Our finding suggests avenues for further exploration to improve clinical outcomes.

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Abstract Background The effectiveness of surgical interventions, whether direct or indirect, for Moyamoya disease (MMD) remains controversial. This study aims to investigate CT perfusion (CTP) as an objective method to evaluate the outcomes of different surgical modalities for adult MMD. Methods The clinical and imaging data of 41 patients who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass and 43 who received encephaloduroarteriosynangiosis (EDAS) were retrospectively analyzed. Intra- and intergroup differences in the Modified Rankin Scale (mRS) score, the change in clinical symptoms, collateral grade, and CTP parameters pre- and postoperatively were compared. Results The overall level of the change in clinical symptoms in the STA-MCA group was higher than in the EDAS group (p

Abstract Objectives To analyze the epidemiological characteristics and trends in death after thoracotomy in children with congenital heart disease (CHD). Methods The clinical data of children with CHD aged 0–14 years who died after thoracotomy in our hospital from January 1, 2005, to December 31, 2020, were retrospectively collected to analyze the characteristics of and trends in postoperative death. Results A total of 502 patients (365 males; 72.7%) died from January 1, 2005, to December 31, 2020, with an average of 31 deaths per year. For these patients, the median age was 2.0 months, the median length of hospital stay was 16.0 days, the median postoperative time to death was 5.0 days, and the median risk adjustment in congenital heart surgery-1 (RACHS-1) score was 3.0. 29.5% underwent emergency surgery, 16.9% had postoperative ECMO support, and 15.9% received postoperative blood purification treatment. In the past 16 years, the deaths of children with CHD under 1 year old accounted for 80.5% of all deaths among children with CHD aged 0–14 years, and deaths (349 cases) under 6 kg accounted for 69.5% of all deaths. Age at death, weight, and disease type were characterized by annual changes. Conclusions The postoperative deaths of children with CHD mainly occurred in infants and toddlers who weighed less than 6.0 kg, and TGA and PA were the most lethal CHDs. The proportion of deaths has been increasing across the years among patients who are young, have a low body weight, and have complex cyanotic CHD.

The access control system is a critical element in intelligent buildings. In this paper, we present SPCL, an innovative access control system designed to facilitate building entry through the use of mobile phones. Our system aims to provide a secure and convenient solution for building access, capitalizing on the widespread availability and capabilities of mobile devices. Additionally, we propose a lightweight authentication protocol to enhance security. The performance of the protocol is measured for different curves at different frequencies, proving that the protocol is more suitable for door lock systems than the benchmark protocol. In addition, we investigated the security and usability of SPCL. Finally, a comparison of the security of human-lock interfaces for smart locks and blockchain-based payment methods are discussed.

This study aimed to assess the stability of thyme essential oil microcapsules (TEOMs) and their impacts on the antioxidant properties and quality of lamb patties. The results demonstrated that gum Arabic effectively enhanced the stability of phenols within the thyme essential oil (TEO), with an optimal core/wall ratio of 1:8. Substituting TEO with TEOMs in lamb patties led to reductions in the thiobarbituric acid content, carbonyl content, sulfhydryl loss, and protein cross-linking. Additionally, the TEOMs positively influenced the mutton patties’ color, texture, microbiological stability, and sensory attributes. These findings substantiate the idea that TEOMs exhibit significant potential as a natural preservative to enhance the quality of mutton patties.

The Chinese urbanization process is undergoing rapid development and intensification. There is, however, little awareness of spatial development in rural areas, particularly in watersheds that are relatively backward. Consequently, human settlements have been disrupted and environmental damage has been caused. The upper reaches of the Minjiang River are not yet aware of the limited space resources and environmental elements due to topography, climate, and other factors, resulting in an unbalanced development. Human settlements and ecological environments are examined in this paper in light of the adaptive development strategy of the upper reaches of the Minjiang River watershed. This paper establishes a “habitat-ecology” variable system for the purpose of adaptability research. The study identified 35 explanatory variables, including 17 in the category of human settlements and 18 in the category of ecological environment. A total of 12 relevant research sample areas have been selected, including five target sample areas and seven comparison sample areas. As a result of differential analysis and correlation research, explanatory variables with high significance were identified as characteristic variables. In addition, a driving mechanism between human settlement and ecological environment is determined using correlation analysis results, optimal subset equations, and independent effects of variables. The results show that in the “habitat-ecology” driving mechanism model: (1) In terms of human settlement, factors such as population density, proportion of construction land, and service scope of medical facilities are the most prominent; (2) In terms of ecological environment, factors such as regional proportion, per capita water area, net flow, and grassland coverage are the most prominent; (3) Based on the element configuration of the above two research subjects, the driving mechanism with human settlement as the driving force and ecological environment as the carrying capacity is obtained.

Small-molecule photothermal agents (PTAs) with intense second near-infrared (NIR-II, 1,000 to 1,700 nm) absorption and high photothermal conversion efficiencies (PCEs) are promising candidates for treating deep-seated tumors such as osteosarcoma. To date, the development of small-molecule NIR-II PTAs has largely relied on fabricating donor–acceptor–donor (D–A–D/D′) structures and limited success has been achieved. Herein, through acceptor engineering, a donor–acceptor–acceptor (D–A–A′)-structured NIR-II aza-boron-dipyrromethene (aza-BODIPY) PTA (SW8) was readily developed for the 1,064-nm laser-mediated phototheranostic treatment of osteosarcoma. Changing the donor groups to acceptor groups produced remarkable red-shifts of absorption maximums from first near-infrared (NIR-I) regions (~808 nm) to NIR-II ones (~1,064 nm) for aza-BODIPYs (SW1 to SW8). Furthermore, SW8 self-assembled into nanoparticles (SW8@NPs) with intense NIR-II absorption and an ultrahigh PCE (75%, 1,064 nm). This ultrahigh PCE primarily originated from an additional nonradiative decay pathway, which showed a 100-fold enhanced decay rate compared to that shown by conventional pathways such as internal conversion and vibrational relaxation. Eventually, SW8@NPs performed highly efficient 1,064-nm laser-mediated NIR-II photothermal therapy of osteosarcoma via concurrent apoptosis and pyroptosis. This work not only illustrates a remote approach for treating deep-seated tumors with high spatiotemporal control but also provides a new strategy for building high-performance small-molecule NIR-II PTAs.

Abstract Background To evaluate trends in the in-hospital mortality rate for pediatric cardiac surgery procedures between 2005 and 2017 in our center, and to discuss the mortality characteristics of children’s CHD after thoracotomy. Methods This retrospective data were collected from medical records of children underwent CHD surgery between 2005 and 2017. Results A total of 19,114 children with CHD underwent surgery and 444 children died, with the in-hospital mortality was 2.3%. Complex mixed defect CHD had the highest fatality rate (8.63%), left obstructive lesion CHD had the second highest fatality rate (4.49%), right to left shunt CHD had the third highest mortality rate (3.51%), left to right shunt CHD had the lowest mortality rate (χ2 = 520.3,P

Pueraria lobata (Willd) (Pueraria montana var. lobata (Willd.) Maesen & S. M. Almeida ex Sanjappa & Predeep) is an important herbal medicine used in many countries. In P. lobata plants showing symptoms of mosaic, yellow spots, and mottling, mixed infection of new viruses provisionally named Pueraria lobata-associated emaravirus (PloAEV, genus Emaravirus), Pueraria lobata-associated crinivirus (PloACV, genus Crinivirus), and isolate CQ of the previously reported kudzu mosaic virus (KuMV-CQ, genus Begomovirus) was confirmed through high-throughput sequencing. PloAEV has five RNA segments, encoding a putative RNA-dependent RNA polymerase, glycoprotein precursor, nucleocapsid protein, movement protein, and P5, respectively. PloACV has two RNA segments, encoding 11 putative proteins. Only PloAEV could be mechanically transmitted from mixed infected symptomatic kudzu to Nicotiana benthamiana plants. All three viruses were detected in 35 symptomatic samples collected from five different growing areas, whereas no viruses were detected in 21 non-symptomatic plants, suggesting a high association between these three viruses. Thus, this study provides new knowledge on the diversity and molecular characteristics of viruses in P. lobata plants affected by the viral disease.

BackgroundSepsis-associated encephalopathy (SAE) is a common complication in septic patients with a higher ICU and hospital mortality in adults and poorer long-term outcomes. Clinical presentation may range from mild confusion to convulsions and deep coma; however, little is known about SAE in children. We aimed to retrospectively analyze the data for children with sepsis, to illustrate the epidemiology, performance, and adverse outcome, and to evaluate the association between risk factors and SAE in children.MethodsAll children with sepsis who were admitted to the Department of Pediatrics, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China from January 2010 to December 2020 were retrospectively analyzed.ResultsA total of 210 patients with sepsis were retrospectively assigned to the SAE and non-SAE groups, of which 91 (43.33%) were diagnosed with SAE with a mortality of 6.70% (14/210). Significant differences were observed in the level of white blood platelet, platelets, international normalized ratio, prothrombin time, activated partial thromboplastin time, total protein, Ccr, UREA, blood urea nitrogen, alanine transaminase, aspartate transaminase, creatine kinase, creatine kinase isoenzymes, lactate dehydrogenase, procalcitonin, and lactic acid (p < 0.05). In the risk assessment scales, significant differences were observed in the modified Glasgow Coma score, PCIS, Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2), Pediatric Sequential Organ Failure Assessment Score, and Pediatric Risk of Mortality III (p < 0.05). The incidence of septic shock, acute kidney disease, liver dysfunction, and coagulation disorder were higher in the SAE group (p < 0.05). The mechanical ventilation time ([6.57 d ± 16.86 d] vs. [2.05 d ± 5.79 d]; p < 0.001), CRRT time ([1.74 d ± 6.77 d] vs. [0.11 d ± 0.63 d]; p < 0.001), ICU stay time ([299.90 h ± 449.50 h] vs. [177.67 h ± 245.36 h]); p < 0.001 was longer than that of non-SAE. Both the PCT, Ca2+, septic shock, PELOD-2, and midazolam were identified as independent risk factors, and fentanyl was a protective factor for SAE in pediatric patients (p < 0.05). The main clinical neurological symptoms consisted of agitation, hypnosia, hypnosis alternates agitated, anterior fontanelle full/bulging/high tension, coma, muscle hypertonia, muscle hypotonia, hyperreflexia, focal seizure, and generalized seizure.ConclusionsThe incidence of SAE in children was found high and the prognosis poor. In this retrospective study, the identified patients were more susceptible to SAE, with an inflammatory storm with hypocalcemia or septic shock. The use of midazolam will increase the occurrence of SAE, whereas fentanyl will reduce the incidence of SAE, and PELOD-2 may predict the occurrence of SAE.

Fog radio access networks has emerged as a promising evolution path for 5G network architecture to satisfy the explosively increasing demands of high-speed data services and massive access requirements of various devices. As a key complement to this path, proximity-based device-to-device (D2D) communications with high transmission rate can better support the above services. For resource allocation in D2D communications, there are two fundamental challenges that should be addressed: 1) how to utilize the mobile characteristics and social relationships among users to enhance the user throughput and 2) how to efficiently allocate the limited resources to guarantee each user’s service satisfaction. In this paper, a D2D dual-link enhanced communication model is developed to improve the throughput of D2D and cellular users (CUs) simultaneously. Then, based on the mobility characteristics and social relationships among users, an optimization problem about resource allocation is formulated and solved with the objective to maximize the user satisfaction. The simulation results verify that our proposed scheme can improve user satisfaction and throughput under limited spectrum resources simultaneously.

Recent studies have shown that traffic safety and efficiency can be substantially improved by vehicle platooning, in which the platoon’ stability is ensured through the exchange of control information among vehicles. So, it is a key issue to share control information efficiently and timely. Proximity-based device-to-device (D2D) communications with high transmission rate, can provide a promising solution to the above issue. In this paper, a platoon leader evaluation-based two-stage platoon formation algorithm is proposed to form stable platoons, which can significantly reduce the spectrum resource overhead and improve the safety of vehicle platooning. After that, we propose a predecessor-following communication mode-based on D2D, ensuring high-rate transmission of control information. Moreover, we propose time division-based intra-platoon and minimum rate guaranteed inter-platoon resource allocation mechanisms, which aims at allocating resources for D2D users efficiently within the platoon and optimize cellular users’ rate, respectively. Numerical results show that the proposed mechanism and algorithm can not only significantly improve spectrum resource utilization, but also guarantee the platoon stability.

Episodic memory consolidation requires activity in hippocampal area CA1. Here the authors report that pharmacogenetic inhibition of CA1 PV+ interneuron firing after fear learning blocks memory consolidation and disrupts associated enhancement in network oscillations and stabilization of functional connectivity patterns.

b-oriented ZSM-5 zeolite film was synthesized on the macropore α-quartz substrate modified with titanium dioxide (TiO2), polyvinyl acetate (PVA), and chitosan (CTS) by hydrothermal crystallization. By comparing the binding energy and b-oriented angle of zeolite film on each modified α-quartz substrate, the orientations, and combinations derived from structure-adsorption relationship were investigated with Material Studio simulation. Furthermore, the effects of calcination temperature and ultraviolet (UV) irradiation time on the surface structure and adsorption activity of TiO2 coating were studied. The increase adsorption potential energy and the formation of Ti-O-Si bind between zeolite crystal phase and substrate facilitate the continuous and uniform zeolite film growth. The TiO2 interlayer with anatase phase after UV irradiation presents a smooth surface with high Ti-OH density, consequently to high selectivity of b-orientation growth for the ZSM-5 crystals. Compared with the traditional ZSM-5, the higher stability has been exhibited with b-oriented ZSM-5 film /TiO2/α-quartz in the MTA reaction, and the methanol conversion and BTX selectivity remained higher than 90 and 70%, after 6 h reaction.

Citrus exocortis viroid (CEVd) is the causal agent of citrus exocortis disease. We employed CEVd-infected ‘Etrog’ citron as a system to study the feedback regulation mechanism using transcriptome analysis in this study. Three months after CEVd infection, the transcriptome of fresh leaves was analyzed, and 1530 differentially expressed genes were detected. The replication of CEVd in citron induced upregulation of genes encoding key proteins that were involved in the RNA silencing pathway such as Dicer-like 2, RNA-dependent RNA polymerase 1, argonaute 2, argonaute 7, and silencing defective 3, as well as those genes encoding proteins that are related to basic defense responses. Many genes involved in secondary metabolite biosynthesis and chitinase activity were upregulated, whereas other genes related to cell wall and phytohormone signal transduction were downregulated. Moreover, genes encoding disease resistance proteins, pathogenicity-related proteins, and heat shock cognate 70 kDa proteins were also upregulated in response to CEVd infection. These results suggest that basic defense and RNA silencing mechanisms are activated by CEVd infection, and this information improves our understanding of the pathogenesis of viroids in woody plants.

Nature Communications 8: Article number: 15039 (2017); Published: 6 April 2017; Updated: 6 July 2017 The original version of the Supplementary Information attached to this Article did not contain Supplementary Figures 11–16 and Supplementary References. The HTML has now been updated to include a corrected version of the Supplementary Information file.