Spying with a pilot's eye: Using eye tracking to investigate pilots' attention allocation and workload during helicopter autorotative gliding.

Flight safety in helicopters is a critical aspect of overall aircraft operational safety management, particularly during engine failures requiring autorotative glide, which makes it extremely challenging for the pilot to land the helicopter successfully. In this study, we evaluated the workload and attention allocation of helicopter pilots under such circumstances. In the experiment, a helicopter flight simulator was used to simulate level flight followed by autorotative glide, with the two phases divided into time segments for data collection. First, the data were visualized using heat maps and saccade sequence diagrams, while changes in eye movement metrics (such as peak value and standard deviation) were statistically analyzed. Finally, the criteria through the inter-criteria correlation (CRITIC) method was used to calculate the weight coefficient for each area of interest. This evaluation system was further applied to analyze and compare the changes in eye-movement data and attention to areas of interest during the two phases. The results revealed a shorter fixation duration, but a greater fixation number during the autorotative glide phase. Further, the mean pupil diameter changed over a larger range than during level flight (in level flight, the mean was 5.229 mm, while the standard deviation was 0.059 mm; in autorotative glide the corresponding values were 5.326 mm and 0.126 mm, respectively). For the tachometer, the weight coefficient matched the color of the heat map (2.7 % and colorless during level flight, but 23.8 % and red during autorotative glide), while those for the airspeed indicator and forward view differed significantly between the two phases. This discrepancy stemmed from the fact that during autorotative glide, the pilots prioritized monitoring aircraft rotation speed and attitude, with a particular focus on the forward view, rotor speed, and airspeed, resulting in a more concentrated attention distribution compared to that achieved during level flight. These results confirmed a significant increase in pilot workload during autorotative glide landing, while a shift was observed from low-frequency long gaze time during level flight to high-frequency short gaze time during autorotative glide. Furthermore, the pilots allocated 81 % of their attention to the tachometer, airspeed indicator, and forward views. Adopting this strategy can improve pilots' landing success and provide flight students with valuable training advice to prevent landing failures when helicopters lose power.

Effects of Thermal Exposure Temperature on Room-Temperature Tensile Properties of Ti65 Alloy.

As a critical material for high-temperature components of aero-engines, the mechanical properties of Ti65 alloy, subjected to high-temperature and long-term thermal exposure, directly affect its service safety. The room-temperature tensile properties of the Ti65 alloy after thermal exposure to temperatures ranging from 450 °C to 650 °C for 100 h were investigated. The results indicate that as the thermal exposure temperature increases, the strength of Ti65 alloy initially increases and then decreases, while ductility exhibits a decreasing trend. The strength of the thermally exposed alloy positively correlates with the size and content of the α2 phase. The ductility of the thermally exposed alloy is comprehensively influenced by the surface oxidation behavior, α2 phase, and silicides. After the prolonged thermal exposure, stress concentration at the crack tips within the oxide layer was enhanced with the increased thickness of the surface TiO2 oxide layer, leading to premature fracture due to reduced alloy ductility. Furthermore, the α2 phase in the matrix promotes the planar slip of dislocations, while silicides at the α/ß phase boundaries hinder dislocation motion, causing dislocation pile-ups. Both behaviors facilitate crack nucleation and deteriorate alloy ductility.

Effect of Infection on the Incidence of Hyperglycemic Hemichorea: A Case-Series.

Objective: To explore the effect of infection on hyperglycemic hemichorea. Methods: The clinical data of 11 patients with hyperglycemic hemichorea admitted to the Affiliated People' s Hospital of Xinxiang Medical College and the Second People's Hospital of Xinxiang were retrospectively analyzed, including gender, age, clinical symptoms, imaging features, blood glucose, glycated hemoglobin, infection indicators, and treatment conditions. Results: Eleven patients had acute or sub-acute onset, including 9 females and 2 males, with an average age of 74.55 years. Nine patients presented with unilateral limb involuntary movement and 2 patients presented with bilateral limb involuntary movement. Imaging findings of 9 patients showed abnormalities in the basal ganglia region. Random blood glucose levels were all elevated at admission, with an average blood glucose value of 26.20 mmol/l. Urine ketone bodies were positive in 2 patients, inflammatory indexes were elevated in 7 patients, symptoms of hypoglycemic treatment and anti-infection treatment in 10 patients disappeared, and symptoms of 1 patient disappeared after improved microcirculation treatment. Conclusion: The disease tends to occur in middle-aged and elderly women, and the blood glucose may fluctuate significantly during the onset. Infection may lead to the occurrence and development of the disease. Active control of blood sugar, inflammation and improvement of brain metabolism can effectively control symptoms and prevent recurrence.

GmBSK1-GmGSK1-GmBES1.5 regulatory module controls heat tolerance in soybean.

INTRODUCTION: Heat stress poses a severe threat to the growth and production of soybean (Glycine max). Brassinosteroids (BRs) actively participate in plant responses to abiotic stresses, however, the role of BR signaling pathway genes in response to heat stress in soybean remains poorly understood. OBJECTIVES: In this study, we investigate the regulatory mechanisms of GmBSK1 and GmBES1.5 in response to heat stress and the physiological characteristics and yield performance under heat stress conditions. METHODS: Transgenic technology and CRISPR/Cas9 technology were used to generated GmBSK1-OE, GmBES1.5-OE and gmbsk1 transgenic soybean plants, and transcriptome analysis, LUC activity assay and EMSA assay were carried out to elucidate the potential molecular mechanism underlying GmBSK1-GmBES1.5-mediated heat stress tolerance in soybean. RESULTS: CRISPR/Cas9-generated gmbsk1 knockout mutants exhibited increased sensitivity to heat stress due to a reduction in their ability to scavenge reactive oxygen species (ROS). The expression of GmBES1.5 was up-regulated in GmBSK1-OE plants under heat stress conditions, and it directly binds to the E-box motif present in the promoters of abiotic stress-related genes, thereby enhancing heat stress tolerance in soybean plants. Furthermore, we identified an interaction between GmGSK1 and GmBES1.5, while GmGSK1 inhibits the transcriptional activity of GmBES1.5. Interestingly, the interaction between GmBSK1 and GmGSK1 promotes the localization of GmGSK1 to the plasma membrane and releases the transcriptional activity of GmBES1.5. CONCLUSION: Our findings suggest that both GmBSK1 and GmBES1.5 play crucial roles in conferring heat stress tolerance, highlighting a potential strategy for breeding heat-tolerant soybean crops involving the regulatory module consisting of GmBSK1-GmGSK1-GmBES1.5.

Different preferences for inorganic carbon influence CO2 flux under Cyanobacteria or Chlorophyta dominance days.

Algae play critical roles in the carbon dioxide (CO2) exchange between the water bodies and the atmosphere. However, the effects of prokaryotic and eukaryotic algae on carbon utilization, CO2 flux, and the underlying mechanisms remain poorly understood. Therefore, this study investigated the differences in carbon preferences and CO2 fluxes under different algal dominance days. Our research revealed that dissolved inorganic carbon (DIC) concentration fluctuations had a limited effect on the relative abundance of algae. However, shifts in dominant algal phyla induced changes in DIC, with Cyanobacteria preferring HCO3- and Chlorophyta preferring CO2. Analysis of the water chemistry balance indicated that the growth of Chlorophyta had a 15.59 times greater effect on CO2 sinks compared with that of Cyanobacteria. During the Cyanobacteria dominance days, the lower DIC concentration did not result in a reduction in CO2 emissions. However, increases in the dissolved organic carbon concentration provided a favorable environment for Cyanobacteria, which promoted CO2 emissions. The CCM model indicated that the growth of Chlorophyta resulted in CO2 uptake rates at least 3.57 times higher and CO2 leakage rates up to 0.97 times lower compared to Cyanobacteria, accelerating CO2 transport into the cell. Overall, CO2 sink was stronger on Chlorophyta dominance days than on Cyanobacteria dominance days. This study emphasized the influence of algal phyla on CO2 fluxes, revealing the significant CO2 sink associated with Chlorophyta. Further research should investigate how to manipulate environmental factors to favor Chlorophyta growth and effectively reduce CO2 emissions.

Spatial and seasonal variations of atmospheric microplastics in high and low population density areas at the intersection of tropical and subtropical regions.

There is limited information regarding spatial and seasonal variations of atmospheric microplastics (MPs) and factors influencing MPs at the intersection of tropical and subtropical regions. A one-year study was conducted at sites in a high-population-density village (HPDV) and a low-population-density village (LPDV) in Taiwan to investigate the characteristics and influencing factors of airborne MPs. The predominant shapes, sizes, and polymer compositions of MPs were fragments, 3 to 25 and 26-50 µm, and polyamide at both sites. Seasonal variation in MP morphologies was not significant. Average MP concentrations were 2.20 ± 2.97 particles/m3 and 1.92 ± 2.35 particles/m3 at the HPDV and LPDV sites, respectively, and did not differ significantly. Higher concentrations and smaller sizes of MPs were found during the summer at both sites, while the predominant wind direction was southerly or southwesterly. In samples with temperatures exceeding 25 °C, the temperature was positively associated with MP concentrations at both the HPDV and LPDV sites. These results reflect that temperature influences the variations in the concentrations and sizes of MPs at our study site. Future research should consider the adverse risks of MP inhalation during the hot season. Moreover, when sites with different population densities and levels of human activity are closed, MP concentrations will not differ significantly between these areas since airflow can transport these particles from high-population-density areas into low-population-density areas in a short time.

Lapatinib: A Potential Therapeutic Agent for Colon Cancer Targeting Ferroptosis.

BACKGROUND: Colon cancer poses a significant threat to the lives of several patients, impacting their quality of life, thus necessitating its urgent treatment. Lapatinib, a new generation of targeted anti-tumor drugs for clinical application, has yet to be studied for its molecular mechanisms in treating colon cancer. OBJECTIVES: This study aimed to uncover the underlying molecular mechanisms through which lapatinib exerts its therapeutic effects in colon cancer treatment. METHODS: We accessed pertinent data on patients with colon cancer from the Cancer Genome Atlas (TCGA) database and performed bioinformatics analysis to derive valuable insights. The cell counting kit-8 (CCK8) assay was employed to assess whether lapatinib has a potential inhibitory effect on the growth and proliferation of HT- 29 cells. Additionally, we employed western blot and real-time quantitative polymerase chain reaction methods to investigate whether lapatinib regulates the expression of the ferroptosis-associated protein GPX4 in HT-29 cells. Furthermore, we utilized specific assay kits to measure the levels of reactive oxygen species (ROS) and malondialdehyde in HT-29 cells treated with lapatinib, aiming to elucidate the precise pattern of cell damage induced by this compound. RESULTS: GPX4 exhibited high expression levels in tissues from patients with colon cancer and was significantly associated with patient prognosis and diagnosis. Lapatinib inhibited the growth and proliferation of the colon cancer cell line HT-29. Additionally, lapatinib suppressed the expression of GPX4 in HT-29 cells, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) partially restored its expression. Lapatinib induced an increase in intracellular ROS levels and malondialdehyde content in HT-29 cells, with Fer-1 partially restoring these levels. CONCLUSION: Our findings demonstrated that lapatinib could effectively suppress the mRNA and protein expression of GPX4 in colon cancer cells, which elevates intracellular levels of ROS and malondialdehyde, ultimately inducing ferroptosis in these cells. This mechanism underscores the potential of lapatinib as a therapeutic strategy for targeting tumors.

Clinical and genomic features of classical and basal transcriptional subtypes in pancreatic cancer.

PURPOSE: Transcriptional profiling of pancreatic cancers (PC) has defined two main transcriptional subtypes, classical and basal. Initial data suggest shorter survival for patients with basal tumors and differing treatment sensitivity to FOLFIRINOX (FFX) and gemcitabine nab-Paclitaxel (GnP) by transcriptional subtype. EXPERIMENTAL DESIGN: We examined 8,743 patients with RNA sequencing from PCs performed at Caris Life Sciences (Phoenix, AZ). Classical and basal subtypes were identified using PurIST algorithm on RNA-sequencing and two cohorts were analyzed: (1) Biomarker cohort included patients with complete molecular profiling data (n = 7,250); (2) Outcomes cohort included patients with metastatic disease with available survival outcomes (n=5,335). RESULTS: In the biomarker cohort, 3,063 tumors (42.2%) were strongly classical (SC), and 2,015 tumors (27.8%) were strongly basal (SB). SC and SB tumors showed strong associations with histologic phenotypes and biopsy site. SB tumors had higher rates of KRAS, TP53, and ARID1A mutations, lower rates of SMAD4 mutation, and transcriptional evidence of epithelial mesenchymal transition. Sixty of 77 cases (78%) maintained their transcriptional subtype between temporally and/or spatially disparate lesions. In the outcomes cohort, SB subtype was associated with shorter overall survival time, regardless of whether they received FFX or GnP as first line chemotherapy. Mutant KRAS allele type was prognostic of outcomes, however this impact was restricted to SC tumors, whereas all mutant KRAS alleles had similarly poor outcomes in SB tumors. CONCLUSIONS: SB subtype is a strong independent predictor of worse outcomes, irrespective of upfront chemotherapy regimen. Clinical trials should investigate PC transcriptional subtypes as a biomarker.

Enhancing chronic migraine preventive therapy: low-level 810 nm laser acupuncture as an add-on treatment for patients with unsatisfactory pharmacological effect, a pilot single-blind randomized controlled trial.

BACKGROUND: Laser acupuncture is a proven non-invasive treatment with effects comparable to traditional acupuncture in different types of headaches, but there is still insufficient evidence for chronic migraine (CM) in adults. We aim to investigate the efficacy and safety of laser acupuncture (LA) as an add-on preventive therapy on CM. METHODS: A single-blind randomized controlled trial was conducted from January 2022 to November 2023. CM patients with unsatisfactory pharmacological effects were randomly assigned in a 1:1 ratio to receive either LA or sham treatment over a course of 8 sessions spanning 4 weeks. The co-primary outcomes were changes in monthly migraine days (MMD) and acute headache medications usage days per month from baseline. Evaluations were taken at baseline (12 weeks before randomization), at 4th week (treatment completed), 8th week and 12th week from baseline. RESULTS: A total of 60 patients (30 in each group) were included in the intention-to-treat analyses. Baseline headache characteristics between trial groups were similar. Compared with the sham group, the LA group had a significant reduction in MMD (5.2 vs. 1.5 days at 8th week, p = 0.015; 7.3 vs. 1.8 days at 12th week, p = 0.001), and acute headache medications usage days per month (3.1 vs. 0.4 days at 4th week, p = 0.007; 3.2 vs. 0.0 days at 8th week, p = 0.005; 3.9 vs. 0.0 days at 12th week, p < 0.001). No serious adverse event was observed in both groups. CONCLUSIONS: Laser acupuncture was effective in reducing MMD and acute headache medications usage with promising safety. Specifically, the efficacy of LA exhibited a progressively more pronounced effect within the follow-up period. We suggested that LA is a promising add-on preventive therapy for CM, and trials focused on investigating the mechanism of LA's effect and its long-term effects on CM prevention are justified. TRIAL REGISTRATION: The study was retrospectively registered at ISRCTN.org Identifier: ISRCTN11208146 ( https://doi.org/10.1186/ISRCTN11208146 ). The registration date: 19, January, 2024. The date of first participant registration: 04, May, 2022.

Comparison of the efficacy and safety of a 730-nm picosecond titanium sapphire laser and a 1064-nm picosecond neodymium yttrium aluminum garnet laser for the treatment of acquired bilateral nevus of Ota-like macules: A split-face, evaluator-blinded, randomized, and controlled pilot trial.

BACKGROUND: The picosecond neodymium yttrium aluminum garnet laser (PNYL) has been successfully used in treating acquired bilateral nevus of Ota-like macules (ABNOM). The 730-nm picosecond titanium sapphire laser (PTSL) is an emerging tool for pigmentary disorders. However, no studies have compared two different wavelengths of picosecond laser for the treatment of ABNOM. AIMS: To compare the efficacy and safety of the 730-nm PTSL with the 1064-nm PNYL in the treatment of ABNOM. METHODS: Fifteen participants with ABNOM were randomized to undergo a single session of either the 730-nm PTSL on one side of the face and 1064-nm PNYL on the other side. Efficacy and safety assessments were performed by blinded visual evaluations at baseline, 12 weeks, and 24 weeks posttreatment. Participants' satisfaction and adverse effects were recorded. RESULTS: Compared to baseline, The 730-nm PTSL-treated side showed better improvement than that of the 1064-nm PNYL-treated side at 24 weeks posttreatment (1.67 ± 1.047 vs. 0.87 ± 0.640, p = 0.027). There were no significant differences in pain sensation and participants' satisfaction between the two laser treatments. CONCLUSIONS: The 730-nm PTSL is more effective than the 1064-nm PNYL in the treatment of ABNOM.

Stabilizing Interlayer Repulsion in Layered Sodium-Ion Oxide Cathodes via Hierarchical Layer Modification.

Layered sodium-ion oxides hold considerable promise in achieving high-performance sodium-ion batteries. However, the notorious phase transformation during charging, attributed to increased O2-─O2- repulsion, results in substantial performance decay. Here, a hierarchical layer modification strategy is proposed to stabilize interlayer repulsion. During desodiation, migrated Li+ from the transition metal layer and anchored Ca2+ in sodium sites maintain the cationic content within the sodium layer. Meanwhile, partial oxygen substitution by fluorine and the involvement of oxygen in redox reactions increase the average valence of the oxygen layer. This sustained cation presence and elevated anion valence collectively mitigate increasing O2-─O2- repulsion during sodium extraction, enabling the Na0.61Ca0.05[Li0.1Ni0.23Mn0.67]O1.95F0.05 (NCLNMOF) cathode to retain a pure P2-type structure across a wide voltage range. Unexpected insights reveal the interplay between different doping elements: the robust Li─F bonds and Ca2+ steric effects suppressing Li+ loss. The NCLNMOF electrode exhibits 82.5% capacity retention after 1000 cycles and a high-rate capability of 94 mAh g-1 at 1600 mA g-1, demonstrating the efficacy of hierarchical layer modification for high-performance layered oxide cathodes.

SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

Exploring the feasibility of remote administration of speech audiometry: A comparative study of conventional and digital methods.

Objective: This study investigated the effectiveness of remote administration of speech audiometry, an essential tool for diagnosing hearing loss and determining its severity. Utilizing two software tools for remote testing, the research aimed to compare these digital methods with traditional, in-person speech audiometry to evaluate their feasibility and accuracy. Design: Participants underwent the Cantonese Hearing in Noise Test (CHINT) under three listening conditions-quiet, noise from the front, and noise from the right side-using three different administration methods: the conventional in-person approach, video conferencing software, and remote access software. Study Sample: Fifty-six Cantonese-speaking adults residing in Hong Kong participated in this study. Results: Analysis revealed no significant differences in CHINT scores among the three administration methods, indicating the potential for remote administration to yield results comparable to those of conventional methods. Conclusions: The findings supported the feasibility of remote speech audiometry using the investigated digital tools. This study paved the way for the wider adoption of tele-audiology practices, particularly in situations where in-person assessments are not possible.

Inferring pattern-driving intercellular flows from single-cell and spatial transcriptomics.

From single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST), one can extract high-dimensional gene expression patterns that can be described by intercellular communication networks or decoupled gene modules. These two descriptions of information flow are often assumed to occur independently. However, intercellular communication drives directed flows of information that are mediated by intracellular gene modules, in turn triggering outflows of other signals. Methodologies to describe such intercellular flows are lacking. We present FlowSig, a method that infers communication-driven intercellular flows from scRNA-seq or ST data using graphical causal modeling and conditional independence. We benchmark FlowSig using newly generated experimental cortical organoid data and synthetic data generated from mathematical modeling. We demonstrate FlowSig's utility by applying it to various studies, showing that FlowSig can capture stimulation-induced changes to paracrine signaling in pancreatic islets, demonstrate shifts in intercellular flows due to increasing COVID-19 severity and reconstruct morphogen-driven activator-inhibitor patterns in mouse embryogenesis.

Comprehensive serum proteomics profiles and potential protein biomarkers for the early detection of advanced adenoma and colorectal cancer.

BACKGROUND: The majority of colorectal cancer (CRC) cases develop from precursor advanced adenoma (AA). With the development of proteomics technologies, blood protein biomarkers have potential applications in the early screening of AA and CRC in the general population. AIM: To identify serum protein biomarkers for the early screening of AA and CRC. METHODS: We collected 43 serum samples from 8 normal controls (NCs), 19 AA patients and 16 CRC patients at China-Japan Friendship Hospital. Quantitative proteomic analysis was performed using liquid chromatography-mass spectrometry/mass spectrometry and data independent acquisition, and differentially expressed proteins (DEPs) with P-values < 0.05 and absolute fold changes > 1.5 were screened out, followed by bioinformatics analysis. Prognosis was further analyzed based on public databases, and proteins expression in tissues were validated by immunohistochemistry. RESULTS: A total of 2132 proteins and 17365 peptides were identified in the serum samples. There were 459 upregulated proteins and 118 downregulated proteins in the NC vs AA group, 289 and 180 in the NC vs CRC group, and 52 and 248 in the AA vs CRC group, respectively. Bioinformatic analysis revealed that these DEPs had different functions and participated in extensive signaling pathways. We also identified DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3 as important proteins for the progression of AA and CRC. Furthermore, VASP (P < 0.01), LBP (P = 0.01), TUBGCP5 (P < 0.01), and DOK3 (P < 0.01) were associated with a poor prognosis. In addition, we propose that LBP and VASP may be more promising protein biomarkers for the early screening of colorectal tumors. CONCLUSION: Our study elucidated the serum proteomic profiles of AA and CRC patients, and the identified proteins, such as LBP and VASP, may contribute to the early detection of AA and CRC.

Exploring the nematicidal mechanisms and control efficiencies of oxalic acid producing Aspergillus tubingensis WF01 against root-knot nematodes.

Background and aims: Root-knot nematodes (RKN; Meloidogyne spp.) are among the highly prevalent and significantly detrimental pathogens that cause severe economic and yield losses in crops. Currently, control of RKN primarily relies on the application of chemical nematicides but it has environmental and public health concerns, which open new doors for alternative methods in the form of biological control. Methods: In this study, we investigated the nematicidal and attractive activities of an endophytic strain WF01 against Meloidogyne incognita in concentration-dependent experiments. The active nematicidal metabolite was extracted in the WF01 crude extract through the Sephadex column, and its structure was identified by nuclear magnetic resonance and mass spectrometry data. Results: The strain WF01 was identified as Aspergillus tubingensis based on morphological and molecular characteristics. The nematicidal and attractive metabolite of A. tubingensis WF01 was identified as oxalic acid (OA), which showed solid nematicidal activity against M. incognita, having LC50 of 27.48 µg ml-1. The Nsy-1 of AWC and Odr-7 of AWA were the primary neuron genes for Caenorhabditis elegans to detect OA. Under greenhouse, WF01 broth and 200 µg ml-1 OA could effectively suppress the disease caused by M. incognita on tomatoes respectively with control efficiency (CE) of 62.5% and 70.83%, and promote plant growth. In the field, WF01-WP and 8% OA-WP formulations showed moderate CEs of 51.25%-61.47% against RKN in tomato and tobacco. The combined application of WF01 and OA resulted in excellent CEs of 66.83% and 69.34% toward RKN in tomato and tobacco, respectively. Furthermore, the application of WF01 broth or OA significantly suppressed the infection of J2s in tomatoes by upregulating the expression levels of the genes (PAL, C4H, HCT, and F5H) related to lignin synthesis, and strengthened root lignification. Conclusion: Altogether, our results demonstrated that A. tubingensis WF01 exhibited multiple weapons to control RKN mediated by producing OA to lure and kill RKN in a concentration-dependent manner and strengthen root lignification. This fungus could serve as an environmental bio-nematicide for managing the diseases caused by RKN.

Screening and Anti-angiogenesis Activity of Chiloscyllium plagiosum Anti-human VEGFR2 Single-domain Antibody.

Recently, the incidence of malignant tumors is on the rise and searching for new treatments on it has become the research priority. Blocking the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is one of the treatment strategies that used in the development of specific anti-angiogenic drugs. The deficiencies in tissue penetration and affinity maturation become the weakness of these drugs in anti-tumors applications. The single heavy chain antibody found in Chiloscyllium plagiosum, which has a low molecular weight and superior tissue penetration of variable region (VNARs), was considered to have the high antigen binding activity and stability. This type of antibody has a simple structure that can be prokaryoticaly expressed, which makes it easily to produce new antiangiogenic target drugs. Specific anti-IgNAR rabbit multiple antibodies have been used to assess the level of VNARs in sharks and have shown a significant enrichment of IgNAR after triple immunization. An anti-VEGFR2 phage library was used for the targeted VNARs screening, and five candidate VNARs sequences were subsequently obtained by phage screening, followed by combined screening with the transcriptome library, and analysis of conserved regions along with 3D modelling matched the VNAR profile. ELISA and cell-based assays showed that two of the VNARs, VNAR-A6 and VNAR-E3, had a superior antigen affinity and anti-angiogenic activity thereby being able to inhibit human Umbilical Vein Endothelial Cells proliferation and migration. The anti-VEGFR2 VNARs derived from the immunized Chiloscyllium plagiosum and screened by phage library, which provide the new research ideas and specific approaches for the development of new drugs. The anti-VEGFR2 VNARs are capable for blocking the VEGF-VEGFR pathway, which of these may contribute to expanding the use of anti-angiogenic drugs.

PARP inhibitor boost the efficacy of photothermal therapy to TNBC through enhanced DNA damage and inhibited homologous recombination repair.

Triple-negative breast cancer (TNBC) could benefit from PARP inhibitors (PARPi) for their frequent defective homologous recombination repair (HR). However, the efficacy of PARPi is limited by their lower bioavailability and high susceptibility to drug resistance, so it often needs to be combined with other treatments. Herein, polydopamine nanoparticles (PDMN) were constructed to load Olaparib (AZD) as two-channel therapeutic nanoplatforms. The PDMN has a homogeneous spherical structure around 100 nm and exhibits a good photothermal conversion efficiency of 62.4%. The obtained AZD-loaded nanoplatform (PDMN-AZD) showed enhanced antitumor effects through the combination of photothermal therapy (PTT) and PARPi. By western blot and flow cytometry, we found that PTT and PARPi could exert synergistic antitumor effects by further increasing DNA double-strand damage (DSBs) and enhancing HR defects. The strongest therapeutic effect of PDMN-AZD was observed in a BRCA-deficient mouse tumor model. In conclusion, the PDMN-AZD nanoplatform designed in this study demonstrated the effectiveness of PTT and PARPi for synergistic treatment of TNBC and preliminarily explained the mechanism.

Modulation of sleep/wake patterns by gephyrin phosphorylation status.

Sleep/wake cycles intricately shape physiological activities including cognitive brain functions, yet the precise molecular orchestrators of sleep remain elusive. Notably, the clinical impact of benzodiazepine drugs underscores the pivotal role of GABAergic neurotransmission in sleep regulation. However, the specific contributions of distinct GABAA receptor subtypes and their principal scaffolding protein, gephyrin, in sleep dynamics remain unclear. The evolving role of synaptic phospho-proteome alterations at excitatory and inhibitory synapses suggests a potential avenue for modulating gephyrin and, consequently, GABAARs for sleep through on-demand kinase recruitment. Our study unveils the distinctive roles of two prevalent GABAA receptor subtypes, α1- and α2-GABAARs, in influencing sleep duration and electrical sleep activity. Notably, the absence of α1-GABAARs emerges as central in sleep regulation, manifesting significant alterations in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during dark or active phases, accompanied by altered electroencephalogram (EEG) patterns across various frequencies. Gephyrin proteomics analysis reveals sleep/wake-dependent interactions with a repertoire of known and novel kinases. Crucially, we identify the regulation of gephyrin interaction with ERK1/2, and phosphorylations at serines 268 and 270 are dictated by sleep/wake cycles. Employing AAV-eGFP-gephyrin or its phospho-null variant (S268A/S270A), we disrupt sleep either globally or locally to demonstrate gephyrin phosphorylation as a sleep regulator. In summary, our findings support the local cortical sleep hypothesis and we unveil a molecular mechanism operating at GABAergic synapses, providing critical insights into the intricate regulation of sleep.

Candidatus Liberibacter asiaticus influences the emergence of the Asian citrus psyllid Diaphorina citri by regulating key cuticular proteins.

The Asian citrus psyllid, Diaphorina citri, is the primary vector of the HLB pathogen, Candidatus Liberibacter asiaticus (CLas). The acquisition of CLas shortens the developmental period of nymphs, accelerating the emergence into adulthood and thereby facilitating the spread of CLas. Cuticular proteins (CPs) are involved in insect emergence. In this study, we investigated the molecular mechanisms underlying CLas-promoted emergence in D. citri via CP mediation. Here, a total of 159 CP genes were first identified in the D. citri genome. Chromosomal location analysis revealed an uneven distribution of these CP genes across the 13 D. citri chromosomes. Proteomic analysis identified 54 differentially expressed CPs during D. citri emergence, with 14 CPs exhibiting significant differential expression after CLas acquisition. Five key genes, Dc18aa-1, Dc18aa-2, DcCPR-24, DcCPR-38 and DcCPR-58, were screened from the proteome and CLas acquisition. The silencing of these 5 genes through a modified feeding method significantly reduced the emergence rate and caused various abnormal phenotypes, indicating the crucial role that these genes play in D. citri emergence. This study provides a comprehensive overview of the role of CPs in D. citri and reveals that CLas can influence the emergence process of D. citri by regulating the expression of CPs. These key CPs may serve as potential targets for future research on controlling huanglongbing (HLB) transmission.