BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Beyond monetary value: how reward type drives cheating in a gender-judgment task.

Background: Investigating the effects of monetary incentives on dishonest behavior provides valuable insights into human integrity and ethical decision-making processes. This study is conducted through the lens of self-concept maintenance theory. Aim: The aim of this study is to examine the influence of different types of rewards (score-based vs. monetary) and their magnitude on dishonest behavior within a gender judgment task. Method: Using a quantitative experimental design, this study involved 116 participants who were randomly assigned to conditions that differed in reward type (score or money) and magnitude (10 yuan vs. 50 yuan). Dishonest behavior was assessed using a gender judgment task with mechanisms to simulate conditions conducive to planned cheating. Results: Results revealed significant differences in dishonesty rates between score and money conditions, with a higher proportion of dishonest participants observed in the score condition compared to the money condition. The timing of initial cheating was earlier in the score condition compared to the money condition. No significant differences were found in the proportion of dishonest participants, the cheating rate, or the timing of initial cheating across reward levels within either condition. The rate of cheating increased over time, suggesting a temporal dynamic in unethical decision making. Conclusion: The study demonstrates that the nature of rewards significantly influences the likelihood of dishonest behavior, with intangible score-based rewards facilitating rationalizations for dishonesty more readily than tangible financial incentives. These findings enrich the understanding of moral psychology by highlighting the complex interplay between reward types, ethical rationalization, and the dynamics of dishonest behavior.

Ocean internal tides suppress tropical cyclones in the South China Sea.

Tropical Cyclones (TCs) are devastating natural disasters. Analyzing four decades of global TC data, here we find that among all global TC-active basins, the South China Sea (SCS) stands out as particularly difficult ocean for TCs to intensify, despite favorable atmosphere and ocean conditions. Over the SCS, TC intensification rate and its probability for a rapid intensification (intensification by ≥ 15.4 m s-1 day-1) are only 1/2 and 1/3, respectively, of those for the rest of the world ocean. Originating from complex interplays between astronomic tides and the SCS topography, gigantic ocean internal tides interact with TC-generated oceanic near-inertial waves and induce a strong ocean cooling effect, suppressing the TC intensification. Inclusion of this interaction between internal tides and TC in operational weather prediction systems is expected to improve forecast of TC intensity in the SCS and in other regions where strong internal tides are present.

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature.

BACKGROUND: The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option. AIM: To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC. METHODS: We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC. RESULTS: Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 ± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases. CONCLUSION: Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.

Supercritical Fluid-extracted Citrus aurantium L. var. amara Engl. Essential Oil Nanoemulsion: Preparation, Characterization, and Its Sleep-promoting Effect.

To overcome the defects of Citrus aurantium L. var. amara Engl. essential oil (CAEO), such as high volatility and poor stability, supercritical fluid-extracted CAEO nanoemulsion (SFE-CAEO-NE) was prepared by the microemulsification method. Emulsifiers comprising Tween 80, polyoxyethylenated castor oil (EL-40), and 1,2-hexanediol, and an oil phase containing SFE-CAEO were used for microemulsification. We examined the physicochemical properties of SFE-CAEO-NE and steam distillation-extracted CAEO nanoemulsion (SDE-CAEO-NE), which were prepared using different concentrations of the emulsifiers. The mean particle size and zeta potential were 21.52 nm and -9.82 mV, respectively, for SFE-CAEO-NE, and 30.58 nm and -6.28 mV, respectively, for SDE-CAEO-NE, at an emulsifier concentration of 15% (w/w). SFE-CAEO-NE displayed better physicochemical properties compared with SDE-CAEO-NE. Moreover, its physicochemical properties were generally stable at different temperatures (-20-60℃), pH (3-8), and ionic strengths (0-400 mM). No obvious variations in particle size, zeta potential, and Ke were observed after storing this nanoemulsion for 30 days at 4℃, 25℃, and 40℃, suggesting that it had good stability. The sleep-promoting effect of SFE-CAEO-NE was evaluated using a mouse model of insomnia. The results of behavioral tests indicated that SFE-CAEO-NE ameliorated insomnia-like behavior. Moreover, SFE-CAEO- NE administration increased the serum concentrations of neurotransmitters such as 5-hydroxytryptamine and γ-aminobutyric acid, and decreased that of noradrenaline in mice. It also exerted a reparative effect on the function of damaged neurons. Overall, SFE-CAEO-NE displayed a good sleep-promoting effect.

Discovery of Fusarium pseudograminearum Causing Crown Rot of Winter Wheat in Xinjiang Uygur Autonomous Region, China.

Fusarium pseudograminearum is an important plant pathogen that invades many crops (Zhang et al. 2018). Since it was first discovered in Australia in 1951, F. pseudograminearum has been reported in many countries and regions and caused huge economic losses (Burgess et al. 2001). In 2012, crown rot of wheat caused by F. pseudograminearum was discovered for the first time in Henan Province, China (Li et al. 2012). Wheat (Triticum aestivum L.) is one of the most important food crops in Xinjiang Uygur Autonomous Region (XUAR), with 1.07 million hectares cultivated in 2020. In June 2023, a survey of crown rot disease was carried out in winter wheat cv. Xindong 20 in Hotan area, XUAR, China (80.148907°E, 37.051474°N). About 5% of wheat plants showed symptoms of crown rot such as browning of the stem base and white head. The disease was observed in 85% of wheat fields. In order to identify the pathogens, 36 pieces of diseased stem basal tissue, 0.5 cm in length, were collected and sterilized with 75% alcohol for 30s and 5% NaOCl solution for 2 min, then rinsed three times with sterile water and placed on potato dextrose agar (PDA) medium at 25°C. A total of 27 isolates with consistent morphological characteristics were obtained using single-spore technique (Leslie and Summerell. 2006), and the isolation rate was 75%. The isolates grew rapidly on PDA, produced large numbers of fluffy white hyphae, and pink pigment accumulated in the medium. The isolates were grown on 2% mung bean flour medium and identified by morphological and molecular methods. Macroconidia were abundant, relatively slender, curved to almost straight, commonly two to seven septate, and averaged 22 to 72 × 1.8 to 4.9 µm. Microconidia were not observed. The morphological characters are consistent with Fusarium (Aoki and O'Donnell. 1999). Two isolates (LP-1 and LP-3) were selected for molecular identification. Primers EF1/EF2 (5'-ATGGGTAAGGARGACAAGAC-3'/5'-GGARGTACCAGTSATCATG-3') were used to amplify a portion of the EF-1α gene (O'Donnell et al. 1998). The two 696 bp PCR products were sequenced and submitted to GenBank. The EF-1α gene sequences (GenBank Accession No: PP062794 and PP062795) shared 99.9% identity (695/696) with published F.pseudograminearum sequences (e.g., OP105187, OP105184, OP105179, OP105173). The identification was further confirmed by F. pseudograminearum species-specific PCR primers Fp1-1/Fp1-2 (Aoki and O'Donnell. 1999). The expected PCR products of 518 bp were produced only in F. pseudograminearum. Pathogenicity tests of LP-1 and LP-3 isolates were performed on 7-day-old seedlings of winter wheat cv. Xindong 20 using the drip inoculation method with a 10-µl of a 106 macroconidia ml-1 suspension near the stem base (Xu et al. 2017). The experiment was repeated five times in a 20 to 25°C greenhouse. Control seedlings were treated with sterile water. After 4 weeks, wheat seedling death and crown browning occurred in the inoculated plants with over 90% incidence. No symptoms were observed in the control plants. The pathogen was reisolated from the inoculated plants by the method described above and identified by morphological and PCR amplification using F. pseudograminearum species-specific primers Fp1-1/Fp1-2. No F. pseudograminearum was isolated from the control plants, fulfilling Koch's postulates. To our knowledge, this is the first report of F. pseudograminearum causing crown rot of winter wheat in XUAR of China. Since F. pseudograminearum can cause great damage to wheat, one of the most important food crops in China, necessary measures should be taken to prevent the spread of F. pseudograminearum to other regions.

Effect of a 3D-printed reconstruction automated matching system for selecting the size of a left double-lumen tube: a study protocol for a prospective randomised controlled trial.

INTRODUCTION: Lung isolation is primarily accomplished using a double-lumen tube (DLT) or bronchial blocker. A precise and accurate size of the DLT is a prerequisite for ensuring its accurate placement. Three-dimensional (3D) reconstruction technology can be used to accurately reproduce tracheobronchial structures to improve the accuracy of DLT size selection. Therefore, we have developed automatic comparison software for 3D reconstruction based on CT data (3DRACS). In this study, we aimed to evaluate the efficiency of using 3DRACS to select the DLT size for endobronchial intubation in comparison with using the 'blind' DLT intubation method to determine the DLT size, which is based on height and sex. METHODS AND ANALYSIS: This is a prospective, single-centre, double-blind randomised controlled trial. In total, 200 patients scheduled for lung resection using a left DLT will be randomly allocated to the 3D group or the control group at a 1:1 ratio. A 3DRACS will be used for the 3D group to determine the size of the DLT, while in the case of the control group, the size of the DLT will be determined according to patient height and sex. The primary outcome is the success rate of placement of the left DLT without fibreoptic bronchoscopy (FOB). The secondary outcomes include the following: successful intubation time, degree of pulmonary atrophy, grade of airway injury, oxygenation during one-lung ventilation, postoperative sore throat and hoarseness, and number of times FOB is used. ETHICS AND DISSEMINATION: Ethical approval has been obtained from our local ethics committee (approval number: SCCHEC-02-2022-155). Written informed consent will be obtained from all participants before randomisation, providing them with clear instructions about the purpose of the study. The results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT06258954.

Physician and Artificial Intelligence Chatbot Responses to Cancer Questions From Social Media.

Importance: Artificial intelligence (AI) chatbots pose the opportunity to draft template responses to patient questions. However, the ability of chatbots to generate responses based on domain-specific knowledge of cancer remains to be tested. Objective: To evaluate the competency of AI chatbots (GPT-3.5 [chatbot 1], GPT-4 [chatbot 2], and Claude AI [chatbot 3]) to generate high-quality, empathetic, and readable responses to patient questions about cancer. Design, Setting, and Participants: This equivalence study compared the AI chatbot responses and responses by 6 verified oncologists to 200 patient questions about cancer from a public online forum. Data were collected on May 31, 2023. Exposures: Random sample of 200 patient questions related to cancer from a public online forum (Reddit r/AskDocs) spanning from January 1, 2018, to May 31, 2023, was posed to 3 AI chatbots. Main Outcomes and Measures: The primary outcomes were pilot ratings of the quality, empathy, and readability on a Likert scale from 1 (very poor) to 5 (very good). Two teams of attending oncology specialists evaluated each response based on pilot measures of quality, empathy, and readability in triplicate. The secondary outcome was readability assessed using Flesch-Kincaid Grade Level. Results: Responses to 200 questions generated by chatbot 3, the best-performing AI chatbot, were rated consistently higher in overall measures of quality (mean, 3.56 [95% CI, 3.48-3.63] vs 3.00 [95% CI, 2.91-3.09]; P < .001), empathy (mean, 3.62 [95% CI, 3.53-3.70] vs 2.43 [95% CI, 2.32-2.53]; P < .001), and readability (mean, 3.79 [95% CI, 3.72-3.87] vs 3.07 [95% CI, 3.00-3.15]; P < .001) compared with physician responses. The mean Flesch-Kincaid Grade Level of physician responses (mean, 10.11 [95% CI, 9.21-11.03]) was not significantly different from chatbot 3 responses (mean, 10.31 [95% CI, 9.89-10.72]; P > .99) but was lower than those from chatbot 1 (mean, 12.33 [95% CI, 11.84-12.83]; P < .001) and chatbot 2 (mean, 11.32 [95% CI, 11.05-11.79]; P = .01). Conclusions and Relevance: The findings of this study suggest that chatbots can generate quality, empathetic, and readable responses to patient questions comparable to physician responses sourced from an online forum. Further research is required to assess the scope, process integration, and patient and physician outcomes of chatbot-facilitated interactions.

Northwestern Pacific Oceanic circulation shaped by ENSO.

The intricate currents of the Northwest Pacific Ocean, with strong manifestations along the westside rim, connect tropical and subtropical gyres and significantly influence East Asian and global climates. The El Niño/Southern Oscillation (ENSO) originates in the tropical Pacific Ocean and disrupts this ocean circulation system. However, the spatiotemporal dependence of the impact of ENSO events has yet to be elucidated because of the complexities of both ENSO events and circulation systems, as well as the increased availability of observational data. We thus combined altimeter and drifter observations to demonstrate the distinct tropical and subtropical influences of the circulation system on ENSO diversity. During El Niño years, the North Equatorial Current, North Equatorial Countercurrent, Mindanao Current, Indonesian Throughflow, and the subtropical Kuroshio Current and its Extension region exhibit strengthening, while the tropical Kuroshio Current weakens. The tropical impact is characterized by sea level changes in the warm pool, whereas the subtropical influence is driven by variations in the wind stress curl. The tropical and subtropical influences are amplified during the Centra Pacific El Niño years compared to the Eastern Pacific El Niño years. As the globe warms, these impacts are anticipated to intensify. Thus, strengthening observation systems and refining climate models are essential for understanding and projecting the enhancing influences of ENSO on the Northwest Pacific Oceanic circulation.

Pd-Catalyzed Three-Component Coupling of Cyclopropenones via Sequential C-C Bond Activation and Allylation.

A novel Pd-catalyzed three-component domino reaction for the stereoselective synthesis of highly functionalized allyl cinnamates has been developed. In this protocol, a sequential process of C-C bond activation and intermolecular allylic substitution was well-organized. The key for this transformation is the in situ generated hydrolysis product of cyclopropenone, which triggered a new reaction with vinylethylene carbonates. The reaction mechanism was investigated, demonstrating the high stereoselectivity and excellent atomic economy in this process.

A novel Burkholderia pyrrocinia strain effectively inhibits Fusarium graminearum growth and deoxynivalenol (DON) production.

BACKGROUND: Fusarium graminearum is a devastating fungal pathogen that poses a significant threat to global wheat production and quality. Control of this toxin-producing pathogen remains a major challenge. This study aimed to isolate strains with antagonistic activity against F. graminearum and at the same time to analyze the synthesis of deoxynivalenol (DON), in order to provide a new basis for the biological control of FHB. RESULTS: Total of 69 microorganisms were isolated from the soil of a wheat-corn crop rotation field, and an antagonistic bacterial strain F12 was identified as Burkholderia pyrrocinia by molecular biology and carbon source utilization. F. graminearum control by strain F12 showed excellent biological activities under laboratory conditions (95.8%) and field testing (63.09%). Meanwhile, the DON content of field-treated wheat grains was detected the results showed that F12 have significantly inhibited of DON, which was further verified by qPCR that F12 produces secondary metabolites that inhibit the expression of DON and pigment-related genes. In addition, the sterile fermentation broth of F12 not only inhibited mycelial growth and spore germination, but also prevented mycelia from producing spores. CONCLUSION: In this study B. pyrrocinia was reported to have good control of FHB and inhibition of DON synthesis. This novel B. pyrrocinia F12 is a promising biological inoculant, providing possibilities for controlling FHB, and a theoretical basis for the development of potential biocontrol agents and biofertilizers for agricultural use. © 2024 Society of Chemical Industry.

Flexible and Free-Standing Metal-Organic Framework Nanowire Paper.

Beyond traditional paper, multifunctional nanopaper has received much attention in recent years. Currently, many nanomaterials have been successfully used as building units of nanopaper. However, it remains a great challenge to prepare flexible and freestanding metal-organic framework (MOF) nanopaper owing to the low aspect ratio and brittleness of MOF nanocrystals. Herein, this work develops a flexible and free-standing MOF nanopaper with MOF nanowires as building units. The manganese-based MOF (Mn-MOF) nanowires with lengths up to 100 µm are synthesized by a facile solvothermal method. Through a paper-making technique, the Mn-MOF nanowires interweave with each other to form a three-dimensional architecture, thus creating a flexible and free-standing Mn-MOF nanowire paper. Furthermore, the surface properties can be engineered to obtain high hydrophobicity by modifying polydimethylsiloxane (PDMS) on the surfaces of the Mn-MOF nanowire paper. The water contact angle reaches 130°. As a proof of concept, this work presents two potential applications of the Mn-MOF/PDMS nanowire paper: (i) The as-prepared Mn-MOF/PDMS nanowire paper is compatible with a commercial printer. The as-printed colorful patterns are of high quality, and (ii) benefiting from the highly hydrophobic surfaces, the Mn-MOF/PDMS nanowire paper is able to efficiently separate oil from water.

Clinical Observation and Cause Analysis of Perioperative Superior Cluneal Neuralgia in Vertebral Augmentation.

BACKGROUND: In our clinical practice, we observed that some osteoporotic vertebral compression fracture patients undergoing vertebral augmentation exhibited pain in the iliac crest region. This pain aligned with the diagnostic criteria for superior cluneal neuralgia (SCN) and affected treatment satisfaction. OBJECTIVE: This study aims to clinically observe patients undergoing vertebral augmentation in a hospital setting and analyze the etiology and risk factors associated with SCN. STUDY DESIGN: Retrospective cohort study. SETTING: Inpatient population of a single center. METHODS: We retrospectively analyzed clinical data from 630 patients who underwent vertebral augmentation in our hospital from March 2022 to March 2023. Fifty-two patients enrolled in the study experienced pain that met the diagnostic criteria for superior cluneal neuralgia during the perioperative period of the vertebral augmentation procedures. Those patients were divided into 2 subgroups according to the conditions involved in the occurrence of SCN: Group A (26 patients) had either no preoperative SCN but developed it postoperatively, or had preoperative SCN that worsened or did not alleviate postoperatively. Group B (26 patients) had preoperative SCN that was relieved postoperatively. Additionally, 52 consecutive patients in March 2022 to March 2023. who did not experience SCN during the perioperative period were selected as the control group (Group C). Variables such as surgical segment, age, height, weight, body mass index, duration of hospitalization, chronic low back pain (CLBP), duration of pain, anesthesia, surgical approach, fracture pattern, preoperative visual analog scale (pre-op VAS) score, intraoperative VAS score, one-day VAS score, one-month VAS score, lumbar sacral angle, and sacral tilt angle were statistically described and analyzed. RESULTS: In our hospital, the incidence of SCN during the perioperative period of vertebral augmentation procedures is 8.25% (52/630). Among all the segments of patients who developed SCN during the perioperative period, the L1 segment had the highest proportion, which was 29.03% and 35.14% in Groups A and B, respectively. Group B and Group C showed significant differences in duration of hospitalization (P = 0.012), pre-op VAS scores (P = 0.026), and CLBP (P < 0.001). Group A had significantly higher VAS scores preoperatively (P = 0.026) and intraoperatively (P = 0.004) and in CLBP (P = 0.001) than did Group C. LIMITATIONS: This is a retrospective study. Single-center noncontrolled studies may introduce selection bias. The small sample size in each group might have also led to bias. CONCLUSION: Perioperative SCN associated with vertebral augmentation is significantly correlated with preoperative VAS scores and CLBP. In addition, intraoperative VAS scores might be a factor contributing to the nonalleviation or exacerbation of postoperative SCN.

Thymic carcinoid with multiple bone metastases: A case report.

BACKGROUND: Thymic carcinoid (TC) is a rare entity among anterior mediastinal malignancies. TCs are neuroendocrine carcinomas that constitute approximately 2%-5% of all thymic epithelial tumors. CASE SUMMARY: The study reported a rare TC with multiple bone metastases. A 77-year-old man presented with a 2-month history of lower back pain and weight loss of 5 kg. Magnetic resonance imaging scans revealed damage to the lumbar spine, sacrocaudal vertebrae and iliac crest, suggesting bone metastasis; computed tomography (CT) scan of the thorax showed a calcified anterior mediastinal mass; positron emission tomography-CT demonstrated multiple abnormal bone signals; and laboratory work-up showed no endocrine abnormalities. Fine-needle aspiration biopsy revealed predominantly single small, round to oval cells with scant cytoplasm and some loose clusters, suggesting endocrine manifestations. The pathological diagnosis was atypical carcinoid, which tend to originate from the thymus and was classified as intermediate-highly invasive. The patient underwent anlotinib-targeted therapy. Anlotinib (12 mg) was administered daily for 2 wk, after which the patient was allowed to rest for 21 d. Follow-up CT after one year demonstrated that the tumor had shrunk by approximately 29% after therapy. Treatment has a long stable disease benefit of more than 2.5 years. CONCLUSION: These findings demonstrated that anlotinib is a promising treatment regimen for patients with TC and multiple bone metastases.

BRAF Mutations in Patients with Myeloid Neoplasms: A Cancer Center Multigene Next-Generation Sequencing Analysis Experience.

BRAF mutations are rare in myeloid neoplasms and are reported to be associated with poor treatment outcomes. The purpose of our study is to characterize BRAF mutations in myeloid neoplasms using a next-generation sequencing (NGS) panel based on the experiences of a single cancer center. We conducted a retrospective review of patients with myeloid neoplasms who underwent the HopeSeq studies between January 2018 and September 2023. A total of 14 patients with myeloid neoplasms carrying BRAF mutations were included in our cohort. The clinical, pathological, and molecular features of these patients were investigated. Our study indicates that BRAF mutations are rare in myeloid neoplasms, constituting only 0.53% (14/2632) of all myeloid neoplasm cases, with the most common BRAF mutation being BRAF V600E (4/14; 28.6%). Interestingly, we observed that six out of seven patients with acute myeloid leukemia (AML) exhibited AML with monocytic differentiation, and all the patients with AML exhibited an extremely poor prognosis compared to those without BRAF mutations. TET2 (5/14; 35.7%), ASXL1 (4/14; 28.6%), and JAK2 (4/14; 28.6%) were the three most frequently co-mutated genes in these patients. Moreover, we noted concurrent KMT2A gene rearrangement with BRAF mutations in three patients with AML (3/7; 42.9%). Our study suggests that although BRAF mutations are rare in myeloid neoplasms, they play a crucial role in the pathogenesis of specific AML subtypes. Furthermore, RAS pathway alterations, including BRAF mutations, are associated with KMT2A gene rearrangement in AML. However, these findings warrant further validation in larger studies.

Stable Inverted Perovskite Solar Cells with Efficiency over 23.0% via Dual-Layer SnO2 on Perovskite.

Perovskite solar cells (PSCs) have shown great potential for reducing costs and improving power conversion efficiency (PCE). One effective method to achieve the latter is to use an all-inorganic charge transport layer (ICTL). However, traditional methods for crystallizing inorganic layers often result in the formation of a powder instead of a continuous film. To address this issue, we designed a dual-layer inorganic electron transport layer (IETL). This dual-layer structure consists of a layer of SnO2 nanocrystals (SnO2 NCs) deposited via a solution process and a dense SnO2 layer deposited through atomic layer deposition (ALD SnO2) to fill the cracks and gaps between the SnO2 NCs. PSCs having these dual-layer SnO2 ETLs achieved a high efficiency of 23.0%. This efficiency surpasses the recorded performance of ICTLs deposited on the perovskite. Furthermore, the PCE is comparable to that achieved with a C60 ETL. Moreover, the high-density structure of the ALD SnO2 layer inhibits the vertical migration of ions, resulting in improved thermal stability. After continuous heating at 85 °C in 10% humidity for 1000 h, the PCE of the dual-layer SnO2 structure decreased by 18%, whereas that of the C60/BCP structure decreased by 36%. The integration of dual-layer SnO2 into PSCs represents a significant advancement in achieving high-performance, commercially viable inverted monolithic PSCs or tandem solar cells.

Ent-eudesmane sesquiterpenoids with anti-neuroinflammatory activity from the marine-derived fungus Eutypella sp. F0219.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.

Whole genome sequencing based analysis of inflammation biomarkers in the Trans-Omics for Precision Medicine (TOPMed) consortium.

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38 465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program (with varying sample size by trait, where the minimum sample size was n = 737 for MMP-1). We identified 22 distinct single-variant associations across 6 traits-E-selectin, intercellular adhesion molecule 1, interleukin-6, lipoprotein-associated phospholipase A2 activity and mass, and P-selectin-that remained significant after conditioning on previously identified associations for these inflammatory biomarkers. We further expanded upon known biomarker associations by pairing the single-variant analysis with a rare variant set-based analysis that further identified 19 significant rare variant set-based associations with 5 traits. These signals were distinct from both significant single variant association signals within TOPMed and genetic signals observed in prior studies, demonstrating the complementary value of performing both single and rare variant analyses when analyzing quantitative traits. We also confirm several previously reported signals from semi-quantitative proteomics platforms. Many of these signals demonstrate the extensive allelic heterogeneity and ancestry-differentiated variant-trait associations common for inflammation biomarkers, a characteristic we hypothesize will be increasingly observed with well-powered, large-scale analyses of complex traits.

Comparative effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide formation in potato chips.

This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips.