The diversity of endophytic fungi in Tartary buckwheat (Fagopyrum tataricum) and its correlation with flavonoids and phenotypic traits.

Tartary buckwheat (Fagopyrum tataricum) is a significant medicinal crop, with flavonoids serving as a crucial measure of its quality. Presently, the artificial cultivation of Tartary buckwheat yields low results, and the quality varies across different origins. Therefore, it is imperative to identify an effective method to enhance the yield and quality of buckwheat. Endophytic fungi reside within plants and form a mutually beneficial symbiotic relationship, aiding plants in nutrient absorption, promoting host growth, and improving secondary metabolites akin to the host. In this study, high-throughput sequencing technology was employed to assess the diversity of endophytic fungi in Tartary buckwheat. Subsequently, a correlation analysis was performed between fungi and metabolites, revealing potential increases in flavonoid content due to endophytic fungi such as Bipolaris, Hymenula, and Colletotrichum. Additionally, a correlation analysis between fungi and phenotypic traits unveiled the potential influence of endophytic fungi such as Bipolaris, Buckleyzyma, and Trichosporon on the phenotypic traits of Tartary buckwheat. Notably, the endophytic fungi of the Bipolaris genus exhibited the potential to elevate the content of Tartary buckwheat metabolites and enhance crop growth. Consequently, this study successfully identified the resources of endophytic fungi in Tartary buckwheat, explored potential functional endophytic fungi, and laid a scientific foundation for future implementation of biological fertilizers in improving the quality and growth of Tartary buckwheat.

Benchmarking the Intrinsic Activity of Transition Metal Oxides for the Oxygen Evolution Reaction with Advanced Nanoelectrodes.

The intrinsic activity assessment of transition metal oxides (TMOs) as key electrocatalysts for the oxygen evolution reaction (OER) has not been standardized due to uncertainties regarding their structure and composition, difficulties in accurately measuring their electrochemically active surface area (ECSA), and deficiencies in mass-transfer (MT) rates in conventional measurements. To address these issues, we utilized an electrodeposition-thermal annealing method to precisely synthesize single-particle TMOs with well-defined structure and composition. Concurrently, we engineered low roughness, spherical surfaces for individual particles, enabling precise measurement of their ECSA. Furthermore, by constructing a conductor-core semiconductor-shell structure, we evaluated the inherent OER activity of perovskite-type semiconductor materials, broadening the scope beyond just conductive TMOs. Finally, using single-particle nanoelectrode technique, we systematically measured individual TMO particles of various sizes for OER, overcoming MT limitations seen in conventional approaches. These improvements have led us to propose a precise and reliable approach to evaluating the intrinsic activity of TMOs, not only validating the accuracy of theoretical calculations but also revealing a strong correlation of OER activity on the melting point of TMOs. This discovery holds significant importance for future high-throughput material research and applications, offering valuable insights in electrocatalysis.

Risk of infection with arboviruses in a healthy population in Pakistan based on seroprevalence.

Infectious diseases caused by arboviruses are a public health concern in Pakistan. However, the studies on data prevalence and threats posed by arboviruses are limited. This study investigated the seroprevalence of arboviruses in a healthy population in Pakistan, including severe fever with thrombocytopenia syndrome virus (SFTSV), Crimean-Congo haemorrhagic fever virus (CCHFV), Tamdy virus (TAMV), and Karshi virus (KSIV) based on a newly established luciferase immunoprecipitation system (LIPS) assays, and Zika virus (ZIKV) by enzyme-linked immunosorbent assays (ELISA). Neutralizing activities against these arboviruses were further examined from the antibody positive samples. The results showed that the seroprevalence of SFTSV, CCHFV, TAMV, KSIV, and ZIKV was 17.37%, 7.58%, 4.41%, 1.10%, and 6.48%, respectively, and neutralizing to SFTSV (1.79%), CCHFV (2.62%), and ZIKV (0.69%) were identified, as well as to the SFTSV-related Guertu virus (GTV, 0.83%). Risk factors associated with the incidence of exposure and levels of antibody response were analysed. Moreover, co-exposure to different arboviruses was demonstrated, as thirty-seven individuals were having antibodies to multiple viruses and thirteen showed neutralizing activity. Males, individuals aged ≤ 40 years, and outdoor workers had high risk of exposure to arboviruses. All these results reveal the substantial risks of infection with arboviruses in Pakistan, and indicate the threat from co-exposure to multiple arboviruses. The findings raise the need for further epidemiologic investigation in expanded regions and populations and the necessity to improve health surveillance in Pakistan.

Metal-Free Electron Donor-Acceptor Pair Enabled Long-Term Stability of Li-CO2 Battery.

The challenges of Lithium-carbon dioxide (Li-CO2) batteries for ensuring long-term cycling stability arise from the thermodynamically stable and electrically insulating discharge products (e.g., Li2CO3), which primarily rely on their interaction with the active materials. To achieve the optimized intermediates, the bifunctional electron donor-acceptor (D-A) pairs are proposed in cathode design to adjust such interactions in the case of B-O pairs. The inclusion of BC2O sites allows for the optimized redistribution of electrons via p-π conjugation. The as-obtained DO-AB pairs endow the enhanced interactions with Li+, CO2, and various intermediates, accompanied by the adjustable growth mode of Li2CO3. The shift from solvation-mediated mode into surface absorption mode in turn manipulates the morphology and decomposition kinetics of Li2CO3. Therefore, the corresponding Li-CO2 battery got twofold improved in both the capacity and reversibility. The cycling prolongs exceed 1300 h and well operates at a wide temperature range (20-50 °C) and different folding angles (0-180°). Such a strategy of introducing electron donor-acceptor pairs provides a distinct direction to optimize the lifetime of Li-CO2 battery from local structure regulation at the atomic scale, further inspiring in-depth understandings for developing electrochemical energy storage and carbon capture technologies.

A dual-targeting antifungal is effective against multidrug-resistant human fungal pathogens.

Drug-resistant fungal infections pose a significant threat to human health. Dual-targeting compounds, which have multiple targets on a single pathogen, offer an effective approach to combat drug-resistant pathogens, although ensuring potent activity and high selectivity remains a challenge. Here we propose a dual-targeting strategy for designing antifungal compounds. We incorporate DNA-binding naphthalene groups as the hydrophobic moieties into the host defence peptide-mimicking poly(2-oxazoline)s. This resulted in a compound, (Gly0.8Nap0.2)20, which targets both the fungal membrane and DNA. This compound kills clinical strains of multidrug-resistant fungi including Candida spp., Cryptococcus neoformans, Cryptococcus gattii and Aspergillus fumigatus. (Gly0.8Nap0.2)20 shows superior performance compared with amphotericin B by showing not only potent antifungal activities but also high antifungal selectivity. The compound also does not induce antimicrobial resistance. Moreover, (Gly0.8Nap0.2)20 exhibits promising in vivo therapeutic activities against drug-resistant Candida albicans in mouse models of skin abrasion, corneal infection and systemic infection. This study shows that dual-targeting antifungal compounds may be effective in combating drug-resistant fungal pathogens and mitigating fungal resistance.

Preparation of Cementitious Materials from Mechanochemically Modified Copper Smelting Slag Compounded with High-Aluminum Fly Ash.

Copper smelting slag discharged from mining and high-aluminum fly ash generated during the combustion of coal for energy production are two typical bulk solid wastes, which are necessary to carry out harmless and resourceful treatment. This research proposed an eco-friendly and economical method for the co-consumption of copper smelting slag and high-aluminum fly ash. Cementitious materials were compounded with copper smelting slag and high-aluminum fly ash as the main materials were successfully prepared, with a 28-d compressive strength up to 31.22 MPa, and the heavy metal leaching toxicity was below the limits of the relevant standards. The optimum mechanical properties of the cementitious materials were obtained by altering the material proportion, ball mill rotation speed, and CaO dosage. Under the combined effect of mechanical ball milling at a suitable speed and chemical activation with a certain alkali concentration, the prepared cementitious materials had an initial activation. The pastes of the cementitious materials generated a gel system during the subsequent hydration process. The two steps together improved the mechanical strength of the cured products. The preparation was simple to operate and offered a high stability of heavy metals. The heavy metal contaminants were kept at a low content throughout the process from raw materials to the prepared cured specimens, which was suitable for application in practical environmental remediation projects and could provide effective solutions for ecological environment construction.

Liver Lipidomics Analysis Revealed the Protective mechanism of Zuogui Jiangtang Qinggan Formula in type 2 diabetes mellitus with non-alcoholic fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatic steatosis, a hallmark of non-alcoholic fatty liver disease (NAFLD), represents a significant global health issue. Liver lipidomics has garnered increased focus recently, highlighting Traditional Chinese Medicine's (TCM) role in mitigating such conditions through lipid metabolism regulation. The Zuogui Jiangtang Qinggan Formula (ZGJTQGF), a longstanding TCM regimen for treating Type 2 Diabetes Mellitus (T2DM) with NAFLD, lacks a definitive mechanism for its lipid metabolism regulatory effects. AIM OF THE STUDY: This research aims to elucidate ZGJTQGF's mechanism on lipid metabolism in T2DM with NAFLD. MATERIALS AND METHODS: The study, utilized db/db mice to establish T2DM with NAFLD models. Evaluations included Hematoxylin-Eosin (HE) and Oil Red O stainedstaining of liver tissues, alongside biochemical lipid parameter analysis. Liver lipidomics and Western blotting further substantiated the findings, systematically uncovering the mechanism of action mechanism. RESULTS: ZGJTQGF notably reduced body weight, and Fasting Blood Glucose (FBG), enhancing glucose tolerance in db/db mice. HE, and Oil Red O staining, complemented by biochemical and liver lipidomics analyses, confirmed ZGJTQGF's efficacy in ameliorating liver steatosis and lipid metabolism anomalies. Lipidomics identified 1571 significantly altered lipid species in the model group, primarily through the upregulation of triglycerides (TG) and diglycerides (DG), and the downregulation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Post-ZGJTQGF treatment, 496 lipid species were modulated, with increased PC and PE levels and decreased TG and DG, showcasing significant lipid metabolism improvement in T2DM with NAFLD. Moreover, ZGJTQGF's influence on lipid synthesis-related proteins was observed, underscoring its anti-steatotic impact through liver lipidomic alterations and offering novel insights into hepatic steatosis pathogenesis. CONCLUSIONS: Liver lipidomics analysis combined with protein verification further demonstrated that ZGJTQGF could ameliorate the lipid disturbance of TG, DG, PC, PE in T2DM with NAFLD, as well as improve fatty acid and cholesterol synthesis and metabolism through De novo lipogenesis pathway.

[Effect of Zuogui Jiangtang Qinggan Formula on lipid metabolism in db/db mouse model of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease].

This study aims to explore the effect of Zuogui Jiangtang Qinggan Formula(ZGJTQGF) on the lipid metabolism in the db/db mouse model of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD) via the insulin receptor(INSR)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/sterol-regulatory element-binding protein 2(SREBP-2) signaling pathway. Twenty-four db/db mice were randomized into positive drug(metformin, 0.067 g·kg~(-1)) and low-(7.5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) ZGJTQGF groups. Six C57 mice were used as the blank group and administrated with an equal volume of distilled water. The mice in other groups except the blank group were administrated with corresponding drugs by gavage for 6 consecutive weeks. At the end of drug administration, fasting blood glucose(FBG) and blood lipid levels were measured, and oral glucose tolerance test was performed. Compared with the blank group, the mice treated with ZGJTQGF showed decreased body mass and liver weight coefficient, lowered levels of FBG, total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL), and weakened liver function. The pathological changes and lipid accumulation in the liver tissue were examined. Western blot was employed to measure the protein levels of INSR, AMPK, p-AMPK, and SREBP-2. Compared with the blank group, the model group showed down-regulated protein levels of INSR and p-AMPK/AMPK and up-regulated protein level of SREBP-2. Compared with the model group, high-dose ZGJTQGF up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2. Low-dose ZGJTQGF slightly up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2, without significant differences. The results suggested that ZGJTQGF may alleviate insulin resistance and improve lipid metabolism in db/db mice by activating the INSR/AMPK/SREBP-2 signaling pathway.

[Tanshinone â ¡_A inhibits ferroptosis via Nrf2 signaling pathway to protect liver in rats of non-alcoholic fatty liver disease].

This study investigated the protective effect of tanshinone Ⅱ_A(TSⅡ_A) on the liver in the rat model of non-alcoholic fatty liver disease(NAFLD) and the mechanism of TSⅡ_A in regulating ferroptosis via the nuclear factor E2-related factor 2(Nrf2) signaling pathway. The rat model of NAFLD was established with a high-fat diet for 12 weeks. The successfully modeled rats were assigned into model group, low-and high-dose TSⅡ_A groups, and inhibitor group, and normal control group was set. Enzyme-linked immunosorbent assay was employed to determine the content of superoxide dismutase(SOD) and malondialdehyde(MDA) in the serum of rats in each group. A biochemical analyzer was used to measure the content of aspartate aminotransferase(AST), alaninl aminotransferase(ALT), total cholesterol(TC), and triglycerides(TG). Hematoxylin-eosin(HE) staining was used to detect pathological damage in liver tissue. Terminal-deoxynucleoitidyl transferase-mediated nick end labeling(TUNEL) was employed to examine the apoptosis of the liver tissue. Oil red O staining, MitoSOX staining, and Prussian blue staining were conducted to reveal lipid deposition, the content of reactive oxygen species(ROS), and iron deposition in liver tissue. Western blot was employed to determine the expression of Nrf2, heme oxygenase-1(HO-1), glutathione peroxidase 4(GPX4), ferroptosis suppressor protein 1(FSP1), B cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) in the liver tissue. The result showed that TSⅡ_A significantly reduced the content of MDA, AST, ALT, TC, and TG in the serum, increased the activity of SOD, decreased the apoptosis rate, lipid deposition, ROS, and iron deposition in the liver tissue, up-regulated the expression of Nrf2, HO-1, FSP1, GPX, and Bcl-2, and inhibited the expression of Bax in the liver tissue of NAFLD rats. However, ML385 partially reversed the protective effect of TSⅡ_A on the liver tissue. In conclusion, TSⅡ_A could inhibit ferroptosis in the hepatocytes and decrease the ROS and lipid accumulation in the liver tissue of NAFLD rats by activating the Nrf2 signaling pathway.

Maximizing the Value of Real-World Data and Real-World Evidence to Accelerate Healthcare Transformation in China: Summary of External Advisory Committee Meetings.

Use of real-world data (RWD) is gaining wide attention. To bridge the gap between diverse healthcare stakeholders and to leverage the impact of Chinese real-world evidence (RWE) globally, a multi-stakeholder External Advisory Committee (EAC) and EAC meetings were initiated, aiming to elucidate the current and evolving RWD landscape in China, articulate the values of RWE in ensuring Chinese patients' equitable access to affordable medicines and solutions, and identify strategic opportunities and partnerships for expansion of RWE generation in China. Chinese and international experts who are clinicians and academic researchers were selected as EAC members based on their professional background and familiarity with RWD/RWE. Three EAC meetings were held quarterly in 2023. Various topics were presented and discussed for insights and suggestions. Nine experts from China, one from South Korea, and two from Europe were selected as EAC members and attended these meetings. Experts' presentations were summarized by theme, including the RWD landscape and RWE enablement in China, as well as global development of a patient-centric ecosystem. Experts' insights and suggestions on maximizing the RWD/RWE value to accelerate healthcare transformation in China were collected. We concluded that though data access, sharing, and quality are still challenging, RWD is developing to support evidence generation in the medicinal product lifecycle, inform clinical practice, and empower patient management in China. RWD/RWE creates value, accelerates healthcare transformation, and improves patient outcomes. Fostering a patient-centric ecosystem across healthcare stakeholders and maintaining global partnerships and collaboration are essential for unlocking the power of RWD/RWE.

Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Effects of carbamazepine on BDNF expression in trigeminal ganglia and serum in rats with trigeminal neuralgia. / å¡é©¬è¥¿å¹³å¯¹ä¸‰å‰ç¥žç»ç—›å¤§é¼ ä¸‰å‰ç¥žç»èŠ‚åŠè¡€æ¸ ä¸­BDNF表达变化的影响.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy. There are numerous treatments for TN, but currently the main clinical approach is to suppress pain by carbamazepine (CBZ). Brain-derived neurotrophic factor (BDNF) is closely related to chronic pain. This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion (TG) and serum of TN via a chronic constriction injury of the infraorbital nerve (ION-CCI) rat model. METHODS: The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group, a TN group, a TN+low-dose CBZ treatment group (TN+20 mg/kg CBZ group), a TN+medium-dose CBZ treatment group (TN+40 mg/kg CBZ group), and a TN+high-dose CBZ treatment group (TN+80 mg/kg CBZ group). The mechanical pain threshold in each group of rats was measured regularly before and after surgery. The expressions of BDNF and tyrosine kinase receptor B (TrkB) mRNA in TGs of rats in different groups were determined by real-time PCR, and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence. Western Blotting was used to detect the protein expression of BDNF, TrkB, extracellular regulated protein kinases (ERK), and phospho-extracellular regulated protein kinases (p-ERK) in TGs of rats in different groups. The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery (all P>0.05). From the 3rd day after operation, the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group (all P<0.01), and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 CBZ mg/kg group was higher than that in the TN group (all P<0.05). The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group (all P<0.05), and those in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than the TN group (all P<0.05). The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group (all P<0.05). The BDNF and neuron-specific nuclear protein (NeuN) were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group (all P<0.05). The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group (P<0.05). The levels of BDNF in the TN+80 mg/kg CBZ group, the TN+40 mg/kg CBZ group, and the TN+20 mg/kg CBZ group were lower than those in the TN group (all P<0.05). Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold (r=-0.650, P<0.01). CONCLUSIONS: CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats, reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway, so as to inhibit TN. The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Trigger a multi-electron reaction by tailoring electronic structure of VO2 toward more efficient aqueous zinc metal batteries.

VO2 (B) is recognized as a promising cathode material for aqueous zinc metal batteries (AZMBs) owing to its remarkable specific capacity and its unique, expansive tunnel structure, which facilitates the reversible insertion and extraction of Zn2+. Nonetheless, challenges such as the inherent instability of the VO2 structure, poor ion/electron transport and a limited capacity due to the low redox potential of the V3+/V4+ couple have hindered its wider application. In this study, we present a strategy to replace vanadium ions by doping Al3+ in VO2. This approach activates the multi-electron reaction (V4+/V5+), to increase the specific capacity and improve the structural stability by forming robust V5+O and Al3+O bonds. It also induces a local electric field by altering the local electron arrangement, which significantly accelerates the ion/electron transport process. As a result, Al-doped VO2 exhibits superior specific capacity, improved cycling stability, and accelerated electronic transport kinetics compared to undoped VO2. The beneficial effects of heterogeneous atomic doping observed here may provide valuable insights into the improvement electrode materials in metal-ion battery systems other than those based on Zn.

Fenestrated Physician Modified Endografts for Endovascular Aortic Arch Repair in Zone 0.

OBJECTIVE: This multicentre study aimed to assess the early and midterm outcomes of fenestrated physician modified endografts (PMEGs) for endovascular aortic arch repair in zone 0. METHODS: Between 2018 and 2022, a retrospective study was conducted in three centres of consecutive patients undergoing endovascular aortic arch repair in zone 0 with PMEGs. Endpoints included technical success, 30 day mortality, major adverse events, secondary interventions, stent stability, target vessel patency, and overall survival. RESULTS: A total of 54 patients (mean age 63 years; 45 males) with aortic arch pathology were included, comprising aortic dissections (n = 32; 59%) and aortic arch aneurysms (n = 22; 41%). Technical success was 98%, and one patient died from stroke within 30 days. Major adverse events included stroke (n = 4; 7%), retrograde type A dissection (RTAD) (n = 3; 6%), and acute kidney injury (n = 2; 4%). During a median follow up of 12 months, there were two deaths (4%) of unknown cause at 1 month and 1.5 months, and no aortic related death. Type Ia, type Ic, and type IIIc endoleaks were observed in 2 (4%), 3 (6%), and 2 (4%) patients, respectively. No vessel stenosis was observed. Re-intervention was required in 10 patients (19%). Estimates of overall survival, freedom from secondary intervention, and freedom from target vessel instability at 1 year were 94.2% (standard error [SE] 3.3%), 81.8% (SE 6.0%), and 92.0% (SE 4.5%), respectively. CONCLUSION: This study demonstrated the efficacy of PMEGs for zone 0 endovascular aortic arch repair, with acceptable technical success and mortality rate. Stroke, RTAD, and re-intervention rates remain a concern for endovascular therapy. A larger population and long term outcomes are required to assess the safety and durability of this technique as a beneficial choice for endovascular aortic arch repair in specialised centres.

Open repair for Sac Expansion after EVAR.

BACKGROUND: This study aimed to examine the outcomes of open surgery techniques involving sacotomy and suturing of the feeding vessels in patients with aneurysm sac expansion after endovascular aneurysm repair (EVAR). METHODS: Fourteen consecutive patients treated with sacotomy and suturing of feeding vessels for expanding aneurysm sacs with type II endoleaks following EVAR, between January 2018 and December 2022, were retrospectively included. All patients underwent preoperative digital subtraction angiography, and attempts were made to embolize the thick feeding vessels to reduce intraoperative bleeding. Age, sex, comorbidities, clinical presentation, aneurysm sac increase, morbidity, mortality, and follow-up were recorded. RESULTS: The median age of the patients was 72.89±5.13 years old, and 13 (92.9%) patients were male. The sac size at the time of the open procedure was 107.89±22.58 mm, and the extent of sac growth at the time of the open procedure was 37.50±18.29 mm. The initial technical success rate of laparotomy and open ligation of the culprit arteries causing type II endoleaks was 92.9% (13/14). Among the patients, five (35.7%) had been treated with interventional embolization before the open procedure. One endograft was removed and replaced by a bifurcated Dacron graft because of distal dislocation in one patient. All patients recovered, and no deaths were recorded postoperatively. No patients had an eventful postoperative course or any subsequent graft-related complications during follow-up. CONCLUSIONS: Open surgical repair involving sacotomy and suturing of the feeding vessels appeared to have good outcomes in the treatment of patients with aneurysm sac expansion caused by type II endoleaks after EVAR. Preoperative embolization of feeding vessels can thus effectively reduce intraoperative bleeding.

Recent progress in retinoblastoma: Pathogenesis, presentation, diagnosis and management.

Retinoblastoma, the primary ocular malignancy in pediatric patients, poses a substantial threat to mortality without prompt and effective management. The prognosis for survival and preservation of visual acuity hinges upon the disease severity at the time of initial diagnosis. Notably, retinoblastoma has played a crucial role in unraveling the genetic foundations of oncogenesis. The process of tumorigenesis commonly begins with the occurrence of biallelic mutation in the RB1 tumor suppressor gene, which is then followed by a cascade of genetic and epigenetic alterations that correspond to the clinical stage and pathological features of the tumor. The RB1 gene, recognized as a tumor suppressor, encodes the retinoblastoma protein, which plays a vital role in governing cellular replication through interactions with E2F transcription factors and chromatin remodeling proteins. The diagnosis and treatment of retinoblastoma necessitate consideration of numerous factors, including disease staging, germline mutation status, family psychosocial factors, and the resources available within the institution. This review has systematically compiled and categorized the latest developments in the diagnosis and treatment of retinoblastoma which enhanced the quality of care for this pediatric malignancy.

Associations of short-term ambient temperature exposure with lung function in middle-aged and elderly people: A longitudinal study in China.

The short-term associations of ambient temperature exposure with lung function in middle-aged and elderly Chinese remain obscure. The study included 19,128 participants from the Dongfeng-Tongji cohort's first (2013) and second (2018) follow-ups. The lung function for each subject was determined between April and December 2013 and re-assessed in 2018, with three parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]) selected. The China Meteorological Data Sharing Service Center provided temperature data during the study period. In the two follow-ups, a total of 25,511 records (average age: first, 64.57; second, 65.80) were evaluated, including 10,604 males (41.57%). The inversely J-shaped associations between moving average temperatures (lag01-lag07) and FVC, FEV1, and PEF were observed, and the optimum temperatures at lag04 were 16.5 °C, 18.7 °C, and 16.2 °C, respectively. At lag04, every 1 °C increase in temperature was associated with 14.07 mL, 9.78 mL, and 62.72 mL/s increase in FVC, FEV1, and PEF in the low-temperature zone (

Pollution control performance of solidified nickel-cobalt tailings on site: Bioavailability of heavy metals and microbial response.

There has been increasing attention given to nickel-cobalt tailings (NCT), which pose a risk of heavy metal pollution in the field. In this study, on site tests and sampling analysis were conducted to assess the physical and chemical characteristics, heavy metal toxicity, and microbial diversity of the original NCT, solidified NCT, and the surrounding soil. The research results show that the potential heavy metal pollution species in NCT are mainly Ni, Co, Mn, and Cu. Simultaneous solidification and passivation of heavy metals in NCT were achieved, resulting in a reduction in biological toxicity and a fivefold increase in seed germination rate. The compressive strength of the original tailings was increased by 20 times after solidification. The microbial diversity test showed that the abundance of microbial community in the original NCT was low and the population was monotonous. This study demonstrates, for the first time, that the use of NCT for solidification in ponds can effectively solidification of heavy metals, reduce biological toxicity, and promote microorganism diversity in mining areas (tended to the microbial ecosystem in the surrounding soil). Indeed, this study provides a new perspective for the environmental remediation of metal tailings.

PXR Activation Relieves Deoxynivalenol-Induced Liver Oxidative Stress Via Malat1 LncRNA m6A Demethylation.

Deoxynivalenol (DON) is a prevalent toxin causing severe liver damage through hepatocellular oxidative stress. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, the unique role of the xenobiotic metabolism factor pregnane X receptor (PXR) in mediating DON-induced hepatocellular oxidative stress is investigated. Treatment with the PXR agonist 3-indole-propionic acid (IPA) alleviates DON-induced oxidative stress and liver injury both in vitro and in vivo. Mechanistically, it is discovered for the first time that PXR agonist IPA directly transactivates the m6A demethylase FTO expression, leading to site-specific demethylation and decreased abundance of YTHDC1-bound Malat1 lncRNA at single-nucleotide resolution. The diminished m6A modification of Malat1 lncRNA reduces its stability and augments antioxidant pathways governed by NRF2, consequently mitigating DON-induced liver injury. Furthermore, Malat1 knockout mice exhibit decreased DON-induced liver injury, emphasizing the role of Malat1 lncRNA in oxidative stress. Collectively, the findings establish that PXR-mediated m6A-dependent Malat1 lncRNA expression determines hepatocyte oxidative stress via m6A demethylase FTO, providing valuable insights into the potential mechanisms underlying DON-induced liver injury and offers potential therapeutic strategies for its treatment.

Reactive Oxygen Species-Responsive Dual Anti-Inflammatory and Antioxidative Nanoparticles for Anterior Uveitis.

Anterior uveitis (AU) is an immune-mediated inflammatory disease that results in iritis, cyclitis, glaucoma, cataracts, and even a loss of vision. The frequent and long-term administration of corticosteroid drugs is limited in the clinic owing to the side effects and patient noncompliance with the drugs. Therefore, specifically delivering drugs to inflammatory anterior segment tissues and reducing the topical application dosage of the drug are still a challenge. Here, we developed dual dexamethasone (Dex) and curcumin (Cur)-loaded reactive oxygen species (ROS)-responsive nanoparticles (CPDC NPs) to treat anterior uveitis. The CPDC NPs demonstrated both anti-inflammatory and antioxidative effects, owing to their therapeutic characteristics of dexamethasone and curcumin, respectively. The CPDC NPs could effectively release dexamethasone and curcumin in the oxidizing physiological environment of the inflammation tissue. The CPDC NPs can effectively internalize by activated macrophage cells, subsequently suppressing the proinflammatory factor expression. Moreover, the CPDC NPs can inhibit ROS and inflammation via nuclear transcription factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway activation. In an endotoxin-induced uveitis rabbit model, the CPDC NPs show a therapeutic effect that is better than that of either free drugs or commercial eye drops. Importantly, the CPDC NPs with a lower dexamethasone dosage could reduce the side effects significantly. Taken together, we believe that the dual-drug-loaded ROS-responsive NPs could effectively target and inhibit inflammation and have the potential for anterior uveitis treatment in clinical practice.