Coumarin-furo[2,3-d]pyrimidone hybrid molecules targeting human liver cancer cells: synthesis, anticancer effect, EGFR inhibition and molecular docking studies.

The design, synthesis and investigation of antitumor activities of some coumarin-furo[2,3-d]pyrimidone hybrid molecules are reported. In vitro, HepG2 cells were used to investigate the cytotoxicity of 6a-n and 10a-n. The results demonstrated that coupling a furopyrimidone scaffold with coumarin through a hydrazide linker can effectively improve their synergistic anticancer activity. The coumarin-furo[2,3-d]pyrimidone combination 10a exhibited significant inhibitory activity against HepG2 cells with IC50 = 7.72 ± 1.56 µM, which is better than those of gefitinib and sorafenib. It is worth mentioning that the coumarin-furo[2,3-d]pyrimidone combination 10a showed excellent inhibition of the EGFR enzymatic activity with IC50 = 1.53 µM and 90% inhibition at 10 µM concentration. In silico investigation predicts the possibility of direct binding between the new coumarin-furo[2,3-d]pyrimidone hybrid molecules and the EGFR. The results suggest that coumarin-furo[2,3-d]pyrimidone hybrid molecules are potential antitumor agents targeting human liver cancer cells.

Soil's Hidden Power: The Stable Soil Organic Carbon Pool Controls the Burden of Persistent Organic Pollutants in Background Soils.

Persistent organic pollutants (POPs) tend to accumulate in cold regions by cold condensation and global distillation. Soil organic matter is the main storage compartment for POPs in terrestrial ecosystems due to deposition and repeated air-surface exchange processes. Here, physicochemical properties and environmental factors were investigated for their role in influencing POPs accumulation in soils of the Tibetan Plateau and Antarctic and Arctic regions. The results showed that the soil burden of most POPs was closely coupled to stable mineral-associated organic carbon (MAOC). Combining the proportion of MAOC and physicochemical properties can explain much of the soil distribution characteristics of the POPs. The background levels of POPs were estimated in conjunction with the global soil database. It led to the proposition that the stable soil carbon pools are key controlling factors affecting the ultimate global distribution of POPs, so that the dynamic cycling of soil carbon acts to counteract the cold-trapping effects. In the future, soil carbon pool composition should be fully considered in a multimedia environmental model of POPs, and the risk of secondary release of POPs in soils under conditions such as climate change can be further assessed with soil organic carbon models.

Hepatocyte mitochondrial DNA mediates macrophage immune response in liver injury induced by trichloroethylene.

We have previously shown that excessive activation of macrophage proinflammatory activity plays a key role in TCE-induced immune liver injury, but the mechanism of polarization is unclear. Recent studies have shown that TLR9 activation plays an important regulatory role in macrophage polarization. In the present study, we demonstrated that elevated levels of oxidative stress in hepatocytes mediate the release of mtDNA into the bloodstream, leading to the activation of TLR9 in macrophages to regulate macrophage polarization. In vivo experiments revealed that pretreatment with SS-31, a mitochondria-targeting antioxidant peptide, reduced the level of oxidative stress in hepatocytes, leading to a decrease in mtDNA release. Importantly, SS-31 pretreatment inhibited TLR9 activation in macrophages, suggesting that hepatocyte mtDNA may activate TLR9 in macrophages. Further studies revealed that pharmacological inhibition of TLR9 by ODN2088 partially blocked macrophage activation, suggesting that the level of macrophage activation is dependent on TLR9 activation. In vitro experiments involving the extraction of mtDNA from TCE-sensitized mice treated with RAW264.7 cells further confirmed that hepatocyte mtDNA can activate TLR9 in mouse peritoneal macrophages, leading to macrophage polarization. In summary, our study comprehensively confirmed that TLR9 activation in macrophages is dependent on mtDNA released by elevated levels of oxidative stress in hepatocytes and that TLR9 activation in macrophages plays a key role in regulating macrophage polarization. These findings reveal the mechanism of macrophage activation in TCE-induced immune liver injury and provide new perspectives and therapeutic targets for the treatment of OMDT-induced immune liver injury.

Ligand-Dominated Activation of CO2 and CS2 by the Putative Nickel Phosphiniminato Intermediates.

Room-temperature photoactivation of the first- and second-generation PN3P-pincer nickel azido complexes 1a and 1b in the presence of CO2 or CS2 afforded N-bound carbamates, dithiocarbamates, and isothiocyanates, providing insights into CO2 and CS2 activation and demonstrating how a seemingly small difference in the ligand structure significantly influences the reactivity. Theoretical calculations disclosed that the charge of the phosphorus atom plays a critical role in determining the nitrogen atom transfer to form a plausible nickel phosphiniminato intermediate.

Detection of SARS-CoV-2 using machine learning-enabled paper-assisted ratiometric fluorescent sensors based on target-induced magnetic DNAzyme.

The development of an advanced analytical platform with regard to SARS-CoV-2 is crucial for public health. Herein, we present a machine learning platform based on paper-assisted ratiometric fluorescent sensors for highly sensitive detection of the SARS-CoV-2 RdRp gene. The assay involves target-induced rolling circle amplification to generate magnetic DNAzyme, which is then detectable using the paper-assisted ratiometric fluorescent sensor. This sensor detects the SARS-CoV-2 RdRp gene with a visible-fluorescence color response. Moreover, leveraging different fluorescence responses, the ResNet algorithm of machine learning assists in accurately identifying fluorescence images and differentiating the concentration of the SARS-CoV-2 RdRp gene with over 99% recognition accuracy. The machine learning platform exhibits exceptional sensitivity and color responsiveness, achieving a limit of detection of 30 fM for the SARS-CoV-2 RdRp gene. The integration of intelligent artificial vision with the paper-assisted ratiometric fluorescent sensor presents a novel approach for the on-site detection of COVID-19 and holds potential for broader use in disease diagnostics in the future.

Nomogram to Predict the Outcome of Ventriculoperitoneal Shunt Among Patients with Non-HIV Cryptococcal Meningitis.

BACKGROUND: The ventriculoperitoneal (VP) shunt is widely acknowledged as a treatment option for managing intracranial hypertension resulting from non-human immunodeficiency virus (HIV) cryptococcal meningitis (CM). Nonetheless, there is currently no consensus on the appropriate surgical indications for this procedure. Therefore, it is crucial to conduct a preoperative evaluation of patient characteristics and predict the outcome of the VP shunt to guide clinical treatment effectively. METHODS: A retrospective analysis was conducted on data from 85 patients with non-HIV CM who underwent VP shunt surgery at our hospital. The analysis involved studying demographic data, preoperative clinical manifestations, cerebrospinal fluid (CSF) characteristics, and surgical outcomes and comparisons between before and after surgery. A nomogram was developed and evaluated. RESULTS: The therapy outcomes of 71 patients improved, whereas 14 cases had worse outcomes. Age, preoperative cryptococcus count, and preoperative CSF protein levels were found to influence the surgical outcome. The nomogram exhibited exceptional predictive performance (area under the curve = 0.896, 95% confidence interval: 0.8292-0.9635). Internal validation confirmed the nomogram's excellent predictive capabilities. Moreover, decision curve analysis demonstrated the nomogram's practical clinical utility. CONCLUSIONS: The surgical outcome of VP shunt procedures patients with non-HIV CM was associated with age, preoperative cryptococcal count, and preoperative CSF protein levels. We developed a nomogram that can be used to predict surgical outcomes in patients with non-HIV CM.

Characterization of a cell wall hydrolase with high activity against vegetative cells, spores and biofilm of Bacillus cereus.

Bacillus cereus is a prevalent foodborne pathogen that induces food poisoning symptoms such as vomiting and diarrhea. Its capacity to form spores and biofilm enables it to withstand disinfectants and antimicrobials, leading to persistent contamination during food processing. Consequently, it is necessary to develop novel and efficient antimicrobial agents to control B. cereus, its spores, and biofilms. Peptidoglycan hydrolases have emerged as a promising and eco-friendly alternative owing to their specific lytic activity against pathogenic bacteria. Here, we identified and characterized a Lysozyme-like cell wall hydrolase Lys14579, from the genome of B. cereus ATCC 14579. Recombinant Lys14579 specifically lysed B. cereus without affecting other bacteria. Lys14579 exhibited strong lytic activity against B. cereus, effectively lysing B. cereus cell within 20 min at low concentration (10 µg/mL). It also inhibited the germination of B. cereus spores and prevented biofilm formation at 12.5 µg/mL. Moreover, Lys14579 displayed good antimicrobial stability with negligible hemolysis in mouse red blood cells and no cytotoxicity against RAW264.7 cells. Notably, Lys14579 effectively inhibited B. cereus in boiled rice and minced meat in a dose-dependent manner. Furthermore, bioinformatics analysis and point mutagenesis experiments revealed that Glu-47 was the catalytic site, and Asp-57, Gln-60, Ser-61 and Glu-63 were active-site residues related with the cell wall lytic activity. Taken together, Lys14579 could be a promising biocontrol agent against vegetative cells, spores, and biofilm of B. cereus in food industry.

Prechiasmatic Transection of the Unilateral Dodge Class â Optic Pathway Glioma without Neurofibromatosis Type 1: Technical Description and Clinical Prognosis.

OBJECTIVE: For unilateral Dodge Class Ⅰ optic pathway glioma (OPG-uDCⅠ) without neurofibromatosis type 1, unilateral isolated optic nerve gliomas before the optic chiasm have been confirmed to possibly cause visual deterioration and poor prognosis. For this type of highly selective localized tumor, we explored surgery as the only treatment method. This article retrospectively analyzed and summarized the clinical data of this case series, with the aim of exploring the main technical details and clinical prognosis. METHODS: Included were patients with OPG-uDCⅠ without neurofibromatosis type 1 and experiencing vision loss on the affected side. The fronto-orbital approach was used, which was mainly divided into 3 parts: intraorbital, optic canal, and intracranial. All patients underwent prechiasmatic resection without any adjuvant treatments. The follow-up period was 3 months after surgery, and magnetic resonance imaging and contralateral visual acuity were reviewed annually after surgery. RESULTS: All OPG-uDCⅠ cases were completely removed without any adjuvant treatments, and there was no recurrence during the follow-up period. Pathological results showed that, except for 1 adult patient with pilomyxoid astrocytoma (World Health Organization grade Ⅱ), the others all had pilocytic astrocytoma (World Health Organization grade Ⅰ). Five patients experienced transient ptosis, and all recovered 3 months after surgery. CONCLUSIONS: For OPG-uDCⅠ without neurofibromatosis type 1, radical prechiasmatic resection of the tumor is possible, without the need for postoperative radiotherapy and chemotherapy.

Photodynamic therapy for treatment of burns: A system review and meta-analysis of animal study.

BACKGROUND AND AIM: Burns are common in both everyday life and war. Shock, infection, and organ dysfunction are major complications, among which infection is the most common and has the highest mortality rate. The aim of this study was to evaluate the effect of photodynamic therapy(PDT) on animals suffering from burns. METHODS: Through searching Embase, PubMed, Web of Science, and the Cochrane Library, only controlled trials were collected to study the effects of PDT on animals with burns. The included studies were evaluated for methodological quality by the MINORS (Methodological Index for Non-Randomized Studies) assessment tool, and the data analysis software was used to analyze the data accordingly. RESULTS: 16 articles were collected between the earliest available date and August 2022. The results of the meta-analysis showed that PDT effectively reduces TNF-α and IL-6 levels in wounds, and increases bFGF and VEGF levels, PDT can also reduce bacterial colonization at the injury site, accelerate the healing of burn wounds, and improve the survival rate. CONCLUSION: PDT has been shown to have positive effects as a treatment for animals suffering from burns. It affects the levels of cytokines, reduces bacterial counts in wounds, promotes wound healing, and improves animal survival rates.

Clinical Characteristics and Prognostic Analysis of Osteolytic and Hyperostosis Sphenoid Orbital Meningiomas: A Single-Center Experience.

Reactive hyperostosis of spheno-orbital meningiomas (SOMs) often occurred in the sphenoid wing, while osteolytic SOMs (O-SOMs) were rarely discussed. This study preliminarily evaluated the clinical characteristics of O-SOMs and analyzed prognostic factors affecting the recurrence of SOMs. We retrospectively analyzed the medical records of consecutive patients who underwent surgery for a SOM between 2015 and 2020. According to the bone changes of sphenoid wing, SOMs were divided into O-SOMs and hyperostosis SOMs (H-SOMs). A total of 31 procedures were performed in 28 patients. All cases were treated by pterional-orbital approach. It was confirmed that 8 cases were O-SOMs and the other 20 cases were H-SOMs. Total tumor resection was performed in 21 cases. There were 19 cases with Ki 67 ≥3%. The patients were followed up for 3 to 87 months. Proptosis improved in all patients. All O-SOMs had no visual deterioration, while 4 H-SOMs cases had visual deterioration. There was no significant difference in clinical outcomes between the two types of SOM. The recurrence of SOM was related to the degree of resection, but not to the type of bone lesions, invasion of cavernous sinus and Ki 67.

Thrombospondin1 mimics rapidly relieve depression via Shank3 dependent uncoupling between dopamine D1 and D2 receptors.

Deficits in astrocyte function contribute to major depressive disorder (MDD) and suicide, but the therapeutic effect of directly reactivating astrocytes for depression remains unclear. Here, specific gains and losses of astrocytic cell functions in the medial prefrontal cortex (mPFC) bidirectionally regulate depression-like symptoms. Remarkably, recombinant human Thrombospondin-1 (rhTSP1), an astrocyte-secreted protein, exerted rapidly antidepressant-like actions through tyrosine hydroxylase (Th)/dopamine (DA)/dopamine D2 receptors (D2Rs) pathways, but not dopamine D1 receptors (D1Rs), which was dependent on SH3 and multiple ankyrin repeat domains 3 (Shank3) in the mPFC. TSP1 in the mPFC might have potential as a target for treating clinical depression.

Risk factors for college students' online lending between different genders-A cross-sectional study in China.

Background: Online lending on campus is given more attention by researchers as its prominent adverse effects on students. The deficiencies of the previous studies on its psychological factors and intervention strategies were only based on qualitative research. Moreover, there is no study on gender differences. Therefore, our study aims to analyze the gender differences in psychological risk factors and give some practical suggestions for the intervention by quantitative methods. Method: This is a cross-sectional survey among medical college students in Chengdu. A total of 984 effective questionnaires were collected. The questionnaire includes demographic data, monthly expenses, self-evaluation for three central psychology causing online lending based on empiricism (conformity, comparison, and hedonism), and three psychological assessment instruments (the Chinese version of the Satisfaction with Life Scale, Egna Minnen av Barndoms Uppfostran, and 144-item version of Temperament and Character Inventory). T-test/χ 2-test and Binary logistic regression were used to analyze the gender differences in variables and the risk factors of online lending for males and females, respectively. Results: The utilization rate of online lending exhibited a significant gender difference (p < 0.001). In addition, there were gender differences in the scores on SWLS and some subscales of C-EMBU and TCI-144. The risk factors for males' were family members using online lending (OR = 5.527, 95% CI = 1.784-17.125) and lower scores on HA (OR = 0.938, 95% CI = 0.888-0.990). The risk factors for females' online lending were family members using online lending (OR = 2.288, 95% CI = 1.201-4.362), hedonism (OR = 5.913, 95% CI = 1.327-26.341), and higher scores on mother's punishment (OR = 1.099, 95% CI = 1.007-1.199). Conclusion: The utilization rate of online lending in males was significantly higher than in females. More attention should be paid to gender differences and the impact of family members' using online lending on students when intervening in online lending.

Percutaneous transluminal angioplasty for radial artery graft stenosis after high-flow superficial temporal artery trunk to middle cerebral artery interposition bypass.

Due to its higher patency rate, a radial artery graft (RAG) is used as an interposition graft for internal-external high-flow bypass more frequently than a saphenous vein graft (SAG). Nevertheless, there are still a few cases of RAG stenosis after bypass surgery. Unfortunately, these reports do not elaborate on the treatment for RAG stenosis. Here, we report the first case of severe RAG stenosis after high-flow STAt-RA-MCA bypass, which was successfully treated with PTA. We speculated that RAG stenosis is associated with the over-length and kinking of the intracranial segment of the RAG instead of vasospasm. We elaborated on the surgical procedure and treatment experience in this particular case in detail. According to our experience, PTA is a type of surgical procedure that can be considered for treating RAG stenosis after high-flow bypass. As long as the surgical procedure can be performed well according to the distance between the stenosis and the anastomosis and the characteristics of the RA tissue, PTA is able to achieve satisfactory long-term results.

A New Concept for Primary Reconstruction of Skull Defects with 3D-Molded PEEK Patch Assisted by Navigation Based on Animal Study.

AIM: To perform an accurate primary repair of temporal bone defects. MATERIAL AND METHODS: The temporal bone defect models were performed in beagles. Extended estimated patches of the defects were predesigned by 3D reconstruction software and molded from polyether ether ketone (PEEK) using a lathe. The precise trimming of the extended PEEK patches was established via coordinate transformation of the patches between the navigation system and the reconstruction software, and in real-time tracing via intraoperative navigation. Trimmed PEEK patches were embedded onto the defects. Blood tests and image examinations were conducted postoperatively. RESULTS: The extended PEEK patches were prepared precisely according to the predesign. Real-time tracing of the actual skull defect profile was performed quickly and accurately. Trimmed skull patches perfectly matched the shape of the defects. No signs of infection, absorption, or translocation of the patches occurred postoperatively, and little epidural effusion was found. CONCLUSION: With the assistance of navigation and 3D reconstruction technology, customized molded PEEK patches can be used for accurate primary repair of temporal bone defects.

A field incubation approach to evaluate the depth dependence of soil biogeochemical responses to climate change.

Soil biogeochemical processes may present depth-dependent responses to climate change, due to vertical environmental gradients (e.g., thermal and moisture regimes, and the quantity and quality of soil organic matter) along soil profile. However, it is a grand challenge to distinguish such depth dependence under field conditions. Here we present an innovative, cost-effective and simple approach of field incubation of intact soil cores to explore such depth dependence. The approach adopts field incubation of two sets of intact soil cores: one incubated right-side up (i.e., non-inverted), and another upside down (i.e., inverted). This inversion keeps soil intact but changes the depth of the soil layer of same depth origin. Combining reciprocal translocation experiments to generate natural climate shift, we applied this incubation approach along a 2200 m elevational mountainous transect in southeast Tibetan Plateau. We measured soil respiration (Rs) from non-inverted and inverted cores of 1 m deep, respectively, which were exchanged among and incubated at different elevations. The results indicated that Rs responds significantly (p < .05) to translocation-induced climate shifts, but this response is depth-independent. As the incubation proceeds, Rs from both non-inverted and inverted cores become more sensitive to climate shifts, indicating higher vulnerability of persistent soil organic matter (SOM) to climate change than labile components, if labile substrates are assumed to be depleted with the proceeding of incubation. These results show in situ evidence that whole-profile SOM mineralization is sensitive to climate change regardless of the depth location. Together with measurements of vertical physiochemical conditions, the inversion experiment can serve as an experimental platform to elucidate the depth dependence of the response of soil biogeochemical processes to climate change.

Influencing factors of life satisfaction among medical staff of rehabilitation departments based on a structural equation model.

Life satisfaction (LS) exhibited gender differences and was associated with age, income, and negative emotions. There is no research on the relationship between professional values and LS, although professional values are essential for medical staff and correlate with negative emotions. This study aimed to explore the relationship between professional values and LS, the action mechanism of influencing factors of LS, and gender differences among medical staff of rehabilitation departments in China. A total of 284 participants (108 men and 176 women) completed the questionnaires. Data were analyzed using SPSS19.0 and Amos21.0. Age, length of service, and anxiety differed significantly between genders. Professional values had a direct effect on LS and an indirect effect on LS via anxiety and depression. Therefore, enhancing professional values and reducing anxiety and depression could increase the medical staff's LS. Moreover, the LS of female medical staff improved with age.

Comparison of nutritional effectiveness and complication rate between early nasojejunal and nasogastric tube feeding in patients with an intracerebral hemorrhage.

BACKGROUND: This study aimed to compare nutritional effectiveness and complication rate between early nasojejunal and nasogastric tube feeding in patients with an intracerebral hemorrhage. METHODS: This was a retrospective study. Eighty patients with an intracerebral hemorrhage were divided into a nasojejunal and a nasogastric tube feeding group. Feeding tubes were placed within 6 h after admission, and enteral feeding began within 2 h after tube placement. The nutritional status and complication rate of the 2 groups were compared before and 2 and 4 weeks after beginning feeding. RESULTS: Serum prealbumin, serum albumin, and hemoglobin levels were significantly higher in the nasojejunal tube feeding group than in the nasogastric tube feeding group at 2 and 4 weeks after beginning feeding (all, p < 0.05). The incidence of gastric retention, pulmonary aspiration, and pneumonia were lower in the early nasojejunal tube feeding group than in the early nasogastric tube feeding group (all, p < 0.05). There was no significant difference in the incidence of diarrhea between the 2 groups. CONCLUSION: Compared with early nasogastric feeding, early nasojejunal feeding provides better nutritional effectiveness and a lower incidence of gastric retention, pulmonary aspiration, and pneumonia in patients with an intracerebral hemorrhage.

Trans-eyebrow supraorbital keyhole approach for suprasellar and intra-suprasellar Rathke cleft cysts: the experience of 16 cases and a literature review.

BACKGROUND: Purely suprasellar and some complex intra-suprasellar Rathke cleft cysts (RCCs) are commonly treated via extended endonasal endoscopic approach or traditional transcranial approach. The feasibility of the trans-eyebrow supraorbital keyhole approach (TSKA) for RCCs was evaluated in this retrospective study. METHODS: A cohort of 16 patients (11 females and 5 males) with RCC was surgically treated via TSKA between January 2013 and November 2021. The medical data and follow-up results were analyzed. RESULTS: Eight patients had a purely suprasellar RCC, and 8 patients had an intra-suprasellar RCC with most of pituitary gland occupying the sellar floor. The mean maximal size of the cysts was 15.4 (range 7-29) mm. Postoperatively, complete cyst drainage was achieved in 15 (93.7%) patients. Preoperative headache, visual dysfunction, and hypopituitarism improved in 12 (100.0%), 3 (75.0%) and 3 (75.0%) patients, respectively, and hyperprolactinemia normalized in all patients. Except 2 (12.5%) cases of transient diabetes insipidus (TDI), no other complications were observed. During the mean follow-up period of 41.0 (range 4-102) months, 1 (6.3%) radiological recurrence was found. CONCLUSIONS: For the treatment of purely suprasellar and some intra-suprasellar RCCs with most of the pituitary occupying the sellar floor, the endoscopic TSKA has the advantage of the minimal invasiveness, excellent visualization of the intrasellar compartment, no additional damage to the underlying pituitary gland, and no risk of CSF leakage. TDI or DI is relative commonly found in treatment of these RCCs. During surgery, care should be taken to avoid damage to the surrounding structures, including the pituitary stalk.

Inductive Stimuli of the Startle Response and Critical Points of Psychological Treatment in a Severe Burn Patient.

Severe burn patients often have anxiety, depression, and stress-related disorders. The case we reported was very nervous and exhibited a long-term high-frequency startle response, which disrupted his sleep seriously and decreased treatment compliance. However, after psychological treatment, his startle response in the daytime and nervousness gradually improved, but the startle response at night remained unchanged. Furthermore, after his wife was given three sessions of psychological treatment to manage her fear of surgery, the startle response at night was significantly reduced. Herein, we summarize the inductive stimuli of the startle response and the critical points of psychological treatment in this case to provide the clinical experience for future research.

How do precipitation events modify the stable isotope ratios in leaf water at Lhasa on the southern Tibetan Plateau?

Serving as a medium between source water and cellulose, leaf water contributes to the isotope ratios (δ18O, δ2H) of plant organic matter, which can be used for paleoclimate reconstruction. This study is the first to examine the diurnal variations in the δ18O and δ2H of leaf water on the southern Tibetan Plateau. The δ18O and δ2H of leaf water were relatively low when precipitation events occurred. In particular, 18O and 2H of leaf water became extremely depleted 5 h after the precipitation event. Our findings demonstrate that precipitation can modify the isotope ratios of leaf water from external and internal causes. First, precipitation events affect meteorological elements, lead to decreases in leaf transpiration, and immediately weaken the isotope enrichment of leaf water ('rapid effect' of precipitation). Second, precipitation events affect the internal plant-soil water cycle process, causing the plant to preferentially use deeper soil water, and the corresponding isotope ratios of leaf water exhibit extremely low values 5 h after precipitation events ('delay effect' of precipitation). This study suggests that researchers need to be cautious in separating the signals of precipitation and hydrological processes when interpreting isotope records preserved in tree-ring cellulose archives from the Tibetan Plateau.