Tonal language experience facilitates the use of spatial cues for segregating competing speech in bimodal cochlear implant listeners.

English-speaking bimodal and bilateral cochlear implant (CI) users can segregate competing speech using talker sex cues but not spatial cues. While tonal language experience allows for greater utilization of talker sex cues for listeners with normal hearing, tonal language benefits remain unclear for CI users. The present study assessed the ability of Mandarin-speaking bilateral and bimodal CI users to recognize target sentences amidst speech maskers that varied in terms of spatial cues and/or talker sex cues, relative to the target. Different from English-speaking CI users, Mandarin-speaking CI users exhibited greater utilization of spatial cues, particularly in bimodal listening.

Discovery of anticancer function of Febrifugine: Inhibition of cell proliferation, induction of apoptosis and suppression steroid synthesis in bladder cancer cells.

Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects. Febrifugine, identified as a quinazoline-type alkaloid compound extracted from the Cytidiaceae family plant Huangchangshan, exhibits heightened sensitivity to bladder cancer cells in comparison to control cells (non-cancer cells) group. The proliferation growth of bladder cancer cells T24 and SW780 was effectively inhibited by Febrifugine, and the IC50 was 0.02 and 0.018 µM respectively. Febrifugine inhibits cell proliferation by suppressing DNA synthesis and induces cell death by reducing steroidogenesis and promoting apoptosis. Combined with transcriptome analysis, Febrifugine was found to downregulate low density lipoprotein receptor-associated protein, lanosterol synthase, cholesterol biosynthesis second rate-limiting enzyme, 7-dehydrocholesterol reductase, flavin adenine dinucleotide dependent oxidoreductase and other factors to inhibit the production of intracellular steroids in bladder cancer T24 cells. The results of animal experiments showed that Febrifugine could inhibit tumor growth. In summary, the effect of Febrifugine on bladder cancer is mainly through reducing steroid production and apoptosis. Therefore, this study contributes to the elucidation of Febrifugine's potential as an inhibitor of bladder cancer and establishes a solid foundation for the future development of novel therapeutic agents targeting bladder cancer.

Cold-inducible RNA binding protein alleviates iron overload-induced neural ferroptosis under perinatal hypoxia insult.

Cold-inducible RNA binding protein (CIRBP), a stress response protein, protects cells from mild hypothermia or hypoxia by stabilizing specific mRNAs and promoting their translation. Neurons subjected to hypobaric hypoxia insult trigger various cell death programs. One of these is ferroptosis, a novel non-apoptotic form of programmed cell death, which is characterized by excessive iron ion accumulation and lipid peroxidation. Here, we establish that CIRBP can regulate neuronal ferroptosis both in vivo and in vitro. We observe that hypoxia leads to neuronal death via intracellular ferrous iron overload and impaired antioxidant systems, accompanied by suppressed CIRBP expression. Genetic enrichment of CIRBP in hippocampal neurons CIRBPTg mice bred with Emx1-Cre mice attenuates hypoxia-induced cognitive deficits and neuronal degeneration. Mechanistically, CIRBP alleviates neuronal ferroptosis and intracellular ferrous ion accumulation by binding to the mitochondrial ferritin (FTMT) 3'UTR to stabilize mRNA and promote its translation. Our novel study shows the critical role of CIRBP in the progression of ferroptosis, and provides promising therapeutic target for hypoxia-induced neurological diseases.

Machine learning-based prediction of the outcomes of cochlear implantation in patients with inner ear malformation.

OBJECTIVE: The objectives of this study are twofold: first, to visualize the structure of malformed cochleae through image reconstruction; and second, to develop a predictive model for postoperative outcomes of cochlear implantation (CI) in patients diagnosed with cochlear hypoplasia (CH) and incomplete partition (IP) malformation. METHODS: The clinical data from patients diagnosed with cochlear hypoplasia (CH) and incomplete partition (IP) malformation who underwent cochlear implantation (CI) at Beijing Tongren Hospital between January 2016 and August 2020 were collected. Radiological features were analyzed through 3D segmentation of the cochlea. Postoperative auditory speech rehabilitation outcomes were evaluated using the Categories of Auditory Performance (CAP) and the Speech Intelligibility Rating (SIR). This study aimed to investigate the relationship between cochlear parameters and postoperative outcomes. Additionally, a predictive model for postoperative outcomes was developed using the K-nearest neighbors (KNN) algorithm. RESULTS: In our study, we conducted feature selection by using patients' imaging and audiological attributes. This process involved methods such as the removal of missing values, correlation analysis, and chi-square tests. The findings indicated that two specific features, cochlear volume (V) and cochlear canal length (CDL), significantly contributed to predicting the outcomes of hearing and speech rehabilitation for patients with inner ear malformations. In terms of hearing rehabilitation, the KNN classification achieved an accuracy of 93.3%. Likewise, for speech rehabilitation, the KNN classification demonstrated an accuracy of 86.7%. CONCLUSION: The measurements obtained from the 3D reconstruction model hold significant clinical relevance. Despite the considerable variability in cochlear morphology across individuals, radiological features remain effective in predicting cochlear implantation (CI) prognosis for patients with inner ear malformations. The utilization of 3D segmentation techniques and the developed predictive model can assist surgeons in conducting preoperative cochlear structural measurements for patients with inner ear malformations. This, in turn, can offer a more informed perspective on the anticipated outcomes of cochlear implantation.

SCD1 sustains brown fat sympathetic innervation and thermogenesis during the long-term cold exposure.

Brown fat adipose tissue (BAT) is a therapeutic potential target to improve obesity, diabetes and cold acclimation in mammals. During the long-term cold exposure, the hyperplastic sympathetic network is crucial for BAT the maintain the highly thermogenic status. It has been proved that the sympathetic nervous drives the thermogenic activity of BAT via the release of norepinephrine. However, it is still unclear that how the thermogenic BAT affects the remodeling of the hyperplastic sympathetic network, especially during the long-term cold exposure. Here, we showed that following long-term cold exposure, SCD1-mediated monounsaturated fatty acid biosynthesis pathway was enriched, and the ratios of monounsaturated/saturated fatty acids were significantly up-regulated in BAT. And SCD1-deficiency in BAT decreased the capacity of cold acclimation, and suppressed long-term cold mediated BAT thermogenic activation. Furthermore, by using thermoneutral exposure and sympathetic nerve excision models, we disclosed that SCD1-deficiency in BAT affected the thermogenic activity, depended on sympathetic nerve. In mechanism, SCD1-deficiency resulted in the unbalanced ratio of palmitic acid (PA)/palmitoleic acid (PO), with obviously higher level of PA and lower level of PO. And PO supplement efficiently reversed the inhibitory role of SCD1-deficiency on BAT thermogenesis and the hyperplastic sympathetic network. Thus, our data provided insight into the role of SCD1-mediated monounsaturated fatty acids metabolism to the interaction between thermogenic activity BAT and hyperplastic sympathetic networks, and illustrated the critical role of monounsaturated fatty acids biosynthetic pathway in cold acclimation during the long-term cold exposure.

Increasing evolution, prevalence, and outbreaks for rift valley fever virus in the process of breaking geographical barriers.

BACKGROUND: Rift valley fever (RVF) is listed as one of prioritized diseases by WHO. This study aims to describe RVF virus' landscape distribution globally, and to insight dynamics change of its evolution, prevalence, and outbreaks in the process of breaking geographical barriers. METHODS: A systematic literature review and meta-analyses was conducted to estimate RVF prevalence by hosts using a random-effect model. Molecular clock-based phylogenetic analyses were performed to estimate RVF virus nucleotide substitution rates using nucleotide sequences in NCBI database. RVF virus prevalence, nucleotide substitution rates, and outbreaks were compared before and after breaking geographical barriers twice, respectively. RESULTS: RVF virus was reported from 26 kinds of hosts covering 48 countries from 1930 to 2022. Since RVF broke geographical barriers, (1) nucleotide substitution rates significantly increased after firstly spreading out of Africa in 2000, (2) prevalence in humans significantly increased from 1.92 % (95 % CI: 0.86-3.25 %) to 3.03 % (95 % CI: 2.09-4.12 %) after it broke Sahara Desert geographical barriers in 1977, and to 5.24 % (95 % CI: 3.81-6.82 %) after 2000, (3) RVF outbreaks in humans and the number of wildlife hosts presented increasing trends. RVF virus spillover may exist between bats and humans, and accelerate viral substitution rates in humans. During outbreaks, the RVF virus substitution rates accelerated in humans. 60.00 % RVF outbreaks occurred 0-2 months after floods and (or) heavy rainfall. CONCLUSION: RVF has the increasing risk to cause pandemics, and global collaboration on "One Health" is needed to prevent potential pandemics.

Colloidal Self-Assembly: From Passive to Active Systems.

Self-assembly fundamentally implies the organization of small sub-units into large structures or patterns without the intervention of specific local interactions. This process is commonly observed in nature, occurring at various scales ranging from atomic/molecular assembly to the formation of complex biological structures. Colloidal particles may serve as micrometer-scale surrogates for studying assembly, particularly for the poorly understood kinetic and dynamic processes at the atomic scale. Recent advances in colloidal self-assembly have enabled the programmable creation of novel materials with tailored properties. We here provide an overview and comparison of both passive and active colloidal self-assembly, with a discussion on the energy landscape and interactions governing both types. In the realm of passive colloidal assembly, many impressive and important structures have been realized, including colloidal molecules, one-dimensional chains, two-dimensional lattices, and three-dimensional crystals. In contrast, active colloidal self-assembly, driven by optical, electric, chemical, or other fields, involves more intricate dynamic processes, offering more flexibility and potential new applications. A comparative analysis underscores the critical distinctions between passive and active colloidal assemblies, highlighting the unique collective behaviors emerging in active systems. These behaviors encompass collective motion, motility-induced phase segregation, and exotic properties arising from out-of-equilibrium thermodynamics. Through this comparison, we aim to identify the future opportunities in active assembly research, which may suggest new application domains.

Impact of Epicardial Adipose Tissue on Right Cardiac Function and Prognosis in Pulmonary Arterial Hypertension.

BACKGROUND: Although epicardial adipose tissue (EAT) is linked to effects on survival in left-sided heart failure, the association between EAT and right-sided heart failure caused by pulmonary arterial hypertension (PAH) remains unknown. RESEARCH QUESTION: What are the potential impacts of EAT volume (EATV) on right ventricular function, biomarkers of myocardial injury, and long-term prognosis in patients with PAH?. STUDY DESIGN AND METHODS: A total of 135 age- and BMI-matched patients with PAH and 49 control subjects were included in this study. EATV was quantified by using cardiac magnetic resonance and was related to clinical correlates, N-terminal pro-brain natriuretic peptide, and cardiac function. Levels of EATV associated with the risk of clinical worsening were evaluated on a continuous scale (restricted cubic splines) and by previously defined centile categories with Cox proportional hazards regression models and Kaplan-Meier survival estimates. RESULTS: Compared with the control subjects, patients with PAH had a lower EATV (ln [EATV], 3.2 ± 0.8 mL vs 3.5 ± 0.7 mL; P = .034). The association of EATV with right ventricular end-diastolic volume (Pnonlinear = .001), right ventricular end-diastolic volume index (P < .001), right ventricular cardiac output (P = .003), N-terminal pro-brain natriuretic peptide (P = .030), and the risk of clinical worsening (P = .014) was U shaped. Compared with individuals with middle-level EATV, multivariable-adjusted hazard ratio for clinical worsening was 6.0 (95% CI, 1.3-27.8) for the individuals with low-level EATV and 6.8 (95% CI, 1.5-30.2) for high-level EATV in patients with PAH. INTERPRETATION: Patients with PAH had a decreased EATV compared with control subjects. EATV exhibited a U-shaped association with right ventricular function and biomarkers of myocardial injury in patients with PAH. Low and high levels of EATV might reduce long-term event-free survival in patients with PAH. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; No. ChiCTR2100049804; www.chictr.org.cn.

[Artificial intelligence-assisted prediction of olfactory disorders in patients with chronic rhinosinusitis].

Objective:To analyze the influencing factors and perform the prediction of olfactory disorders in patients with chronic rhinosinusitis（CRS） based on artificial intelligence. Methods:The data of 75 patients with CRS who underwent nasal endoscopic surgery from October 2021 to February 2023 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively. There were 53 males and 22 females enrolled in the study, with a median age of 42.0 years old. The CRS intelligent microscope interpretation system was used to calculate the proportion of area glands and blood vessels occupy in the pathological sections of each patient, and the absolute value and proportion of eosinophils, lymphocytes, plasma cells and neutrophils. The patients were grouped according to the results of the Sniffin' Sticks smell test, and the clinical baseline data, differences in nasal mucosal histopathological characteristics, laboratory test indicators and sinus CT were compared between the groups. Determine the independent influencing factors of olfactory disorders and receiver operating characteristic curves（ROC） were used to evaluate the performance of the prediction model. Statistical analysis was performed using SPSS 25.0 software. Results:Among the 75 CRS patients, 25 cases（33.3%） had normal olfaction and 50 cases（66.7%） had olfactory disorders. Multivariate Logistic regression analysis showed that tissue eosinophils percentage（OR=1.032, 95%CI 1.002-1.064, P=0.036）, Questionnaire of olfactory disorders-Negative statement（QOD-NS）（OR=1.079, 95%CI 1.004-1.160, P=0.040） and Anterior olfactory cleft score（AOCS）（OR=2.672, 95%CI 1.480-4.827, P=0.001） were independent risk factors for olfactory disorders in CRS patients. Further research found that the area under the ROC curve（AUC） of the combined prediction model established by the tissue eosinophil percentage, QOD-NS and AOCS was 0.836（95%CI 0.748-0.924, P<0.001）, which is better than the above single factor prediction model in predicting olfactory disorders in CRS. Conclusion:Based on pathological artificial intelligence, tissue eosinophil percentage, QOD-NS and AOCS are independent risk factors for olfactory disorders in CRS patients, and the combination of the three factors has a good predictive effect on CRS olfactory disorders.

Characterizing systemic physiological effects on the blood oxygen level dependent signal of resting-state fMRI in time-frequency space using wavelets.

Systemic physiological dynamics, such as heart rate variability (HRV) and respiration volume per time (RVT), are known to account for significant variance in the blood oxygen level dependent (BOLD) signal of resting-state functional magnetic resonance imaging (rsfMRI). However, synchrony between these cardiorespiratory changes and the BOLD signal could be due to neuronal (i.e., autonomic activity inducing changes in heart rate and respiration) or vascular (i.e., cardiorespiratory activity facilitating hemodynamic changes and thus the BOLD signal) effects and the contributions of these effects may differ spatially, temporally, and spectrally. In this study, we characterize these brain-body dynamics using a wavelet analysis in rapidly sampled rsfMRI data with simultaneous pulse oximetry and respiratory monitoring of the Human Connectome Project. Our time-frequency analysis across resting-state networks (RSNs) revealed differences in the coherence of the BOLD signal and heartbeat interval (HBI)/RVT dynamics across frequencies, with unique profiles per network. Somatomotor (SMN), visual (VN), and salience (VAN) networks demonstrated the greatest synchrony with both systemic physiological signals when compared to other networks; however, significant coherence was observed in all RSNs regardless of direct autonomic involvement. Our phase analysis revealed distinct frequency profiles of percentage of time with significant coherence between BOLD and systemic physiological signals for different phase offsets across RSNs, suggesting that the phase offset and temporal order of signals varies by frequency. Lastly, our analysis of temporal variability of coherence provides insight on potential influence of autonomic state on brain-body communication. Overall, the novel wavelet analysis enables an efficient characterization of the dynamic relationship between cardiorespiratory activity and the BOLD signal in spatial, temporal, and spectral dimensions to inform our understanding of autonomic states and improve our interpretation of the BOLD signal.

Comprehensive strength evaluation system of commercial centres based on multi-source data: a case of Hefei central city.

Urban commercial centres are the most concentrated areas of economic activity. Understanding the spatial distribution pattern and comprehensive strength of urban commercial centres is important to guide the reasonable graded allocation of urban commercial space, spatial structure optimization and sustainable development of the commercial economy. Herein, mobile phone signalling data are used to identify the functional connection between recreational and residential places and local spatial autocorrelation analysis is used to identify the 24 commercial centres in the central city of Hefei. The comprehensive strength evaluation system of commercial centres is constructed from their basic conditions and customer consumption behaviours, and their comprehensive strength indices are accordingly measured and graded. The spatial distribution characteristics of commercial centres at all levels are analysed, and optimisation suggestions are made for the whole area and region. The following conclusions are drawn from the results of this study. (1) Compared to traditional single-perspective evaluations, the developed comprehensive strength evaluation system considers supply and demand perspectives for commercial centres, providing a more holistic and accurate portrayal of the strengths of various centres within a region. (2) The current commercial centres are characterised by 'large dispersion and small concentration' in spatial and hierarchical distribution. (3) The commercial centres in Hefei have formed a relatively complete 'first, second, and third level' commercial centre system, with the first level as the core and relying on the urban road system to form a network spatial connection. (4) Most of the commercial centres are concentrated in the First Ring Road, Swan Lake in the Government Affairs District and Binhu Century Town Estate, while most areas north of the Second Ring Road and Binhu New District still lack large-scale commercial centres. This study provides a technical reference for analysing urban commercial spatial structure patterns and provides decision support for optimising the spatial layout of urban commercial service functions.

Evaluating the role of serum uric acid in the risk stratification and therapeutic response of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD).

Background: Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease that negatively impacts quality of life, exercise capacity, and mortality. This study sought to investigate the relationship between serum uric acid (UA) level and the disease severity and treatment response of patients with PAH and congenital heart disease (PAH-CHD). Methods: This study included 225 CHD patients and 40 healthy subjects. Serum UA was measured in all patients, and UA levels and haemodynamic parameters were re-evaluated in 20 patients who had received PAH-specific drug treatment for at least 7 ± 1 month. Results: Serum UA levels were significantly higher in PAH-CHD patients than in CHD patients with a normal pulmonary artery pressure and normal subjects (347.7 ± 105.7 µmol/L vs. 278.3 ± 84.6 µmol/L; 347.7 ± 105.7 µmol/L vs. 255.7 ± 44.5 µmol/L, p < 0.05). UA levels in the intermediate and high risk groups were significantly higher than those in the low-risk group (365.6 ± 107.8 µmol/L vs. 311.2 ± 82.8 µmol/L; 451.6 ± 117.6 µmol/L vs. 311.2 ± 82.8 µmol/L, p < 0.05). Serum UA levels positively correlated with mean pulmonary arterial pressure, WHO functional class, pulmonary vascular resistance, and NT-proBNP (r = 0.343, 0.357, 0.406, 0.398; p < 0.001), and negatively with mixed venous oxygen saturation (SvO2) and arterial oxygen saturation (SaO2) (r = -0.293, -0.329; p < 0.001). UA significantly decreased from 352.7 ± 97.5 to 294.4 ± 56.8 µmol/L (p = 0.001) after PAH-specific drug treatment for at least 6 months, along with significant decreases in mean pulmonary arterial pressure and pulmonary vascular resistance and increases in cardiac index and mixed SvO2. Conclusion: Serum UA can be used as a practical and economic biomarker for risk stratification and the evaluation of PAH-specific drug treatment effects for patients with PAH-CHD.

Effectiveness of social media with or without wearable devices to improve physical activity and reduce sedentary behavior: A randomized controlled trial of Chinese postgraduates.

The present study was aimed to verify whether an integrating of wearable activity tracker device and a social media intervention strategy would be better than a standalone social media intervention for improving physical activity (PA) and reducing sedentary time for Chinese postgraduate population. A total of 42 full-time postgraduate students participated in this study, which were randomized to receive a 4-week social media intervention through WeChat either with (Wearable Device group) or without (control group) a wearable activity tracker device. Energy expenditure, step counts, moderate to vigorous physical activity time (MVPA) and sedentary time were assessed before and after the intervention. Besides, anthropometric parameters of body weight, body mass index, body fat rate, waist-to-hip ratio, as well as self-reported quality of life were also evaluated. It was found that both energy expenditure and step counts were significantly increased, while sedentary time was significantly reduced during the post-intervention test compared to the baseline test for Wearable Device group. No significant difference of PA was found for the control group. The results demonstrated that the integrating of wearable activity tracker device and a social media intervention was effective in promoting PA, while a standalone social media intervention may have no effect on the influence of PA for Chinese postgraduates.

Analysis of relationship between P wave dispersion and diagnosis of pulmonary arterial hypertension and risk stratification.

BACKGROUND: The aim of this study was to measure the P-wave dispersion(PWD) in the ECG of patients with pulmonary arterial hypertension(PAH). METHODS: A total of 103 PAH patients were collected, including 55 patients related with congenital heart disease(CHD) and 44 patients with idiopathic pulmonary arterial hypertension(IPAH). In addition, 30 CHD patients without PAH (nPAH-CHD group) and 30 healthy controls (HCG group) were collected as control. Patients in the PAH group were categorized into the low-risk group (30 cases), moderate-risk group (53 cases) and high-risk group (20 cases), followed by comparison of PWD difference between groups. The ROC curve was used to evaluate the diagnostic efficacy of PWD on PAH-CHD and IPAH. RESULTS: The levels of PWD and maximum P wave duration(Pmax) in PAH-CHD and IPAH group were significantly higher than those in nPAH-CHD and HCG group (P < 0.05). PWD level was positively correlated with right ventricular end-diastolic diameter(RVD), right atrial end-systolic diameter(RAS), mean pulmonary arterial pressure(mPAP), pulmonary vascular resistance(PVR)(r = 0.407, 0.470, 0.477, 0.423, P < 0.001), and was negatively correlated with systolic displacement of tricuspid valve annulus(TAPSE) level (r = -0.551, P < 0.001). After risk quantification in 103 PAH patients, we found that PWD was significantly different among the low-risk, moderate-risk and high-risk groups (43.89 ± 9.91 vs. 51.29 ± 6.61, 62.15 ± 10.44, P < 0.001). CHD-PAH and IPAH were identified by PWD with a cut off value of 41.5 ms (P < 0.001), and a cut off value of 41.45 ms (P < 0.001), respectively. CONCLUSIONS: PWD might be an effective ECG indicator for PAH, which might be used as a relatively economical indicator for PAH patients to assist in early diagnosis, disease severity assessment and prognosis evaluation.

Effects of microplastics on functional genes related to CH4 and N2O metabolism in bacteriophages during manure composting and its planting applications.

Microplastics (MPs), as a new type of pollutant, widely exist in livestock and poultry breeding and agricultural soils. However, research on MPs pollution on greenhouse gas emissions in combined planting and breeding systems is lacking, especially from the perspective of phage horizontal gene transfer. Therefore, this paper explores the effects of MPs on functional genes related to CH4 and N2O metabolism in bacteriophages during manure composting and its planting applications. The results of the study indicated that the addition of MPs had an impact on both the physicochemical properties and microbial community structure of manure during the composting process and on the compost-applied rhizosphere soil of lactuca (Lactuca sativa). Specifically, on day 7 of composting, mcrA/pmoA and (nirS+nirK) levels in bacteria in the MP group significantly increased. Additionally, it was observed that the MP group had higher average temperatures during the high-temperature period of composting, which led to a rapid reduction in phages. However, the phage levels quickly recovered during the cooling period. Furthermore, the addition of MPs to the rhizosphere soil resulted in higher levels of nirK. These changes may affect greenhouse gas emissions.

Tunable Self-Thermophoretic Nanomotors with Polymeric Coating.

Thermophoretic micro/nanomotors (MNMs) generate self-propulsion without a chemical reaction. Intrinsically, this promises excellent biocompatibility and is thus suitable for biomedical applications. However, their propulsion efficiency is severely limited due to the poor understanding of the thermophoretic process, which dominates the conversion from thermal energy into mechanical movement. We here developed a series of self-thermophoresis light-powered MNMs with variable surface coatings and discovered obvious self-thermophoresis propulsion enhancement of the polymeric layer. An intrinsically negative self-thermophoretic movement is also observed for the first time in the MNM system. We propose that enthalpic contributions from polymer-solvent interactions should play a fundamental role in the self-thermophoretic MNMs. Quantitative microcalorimetry and molecular dynamics simulations are performed to support our hypothesis. The polymer solvation enthalpy and coating thickness influences on self-thermophoresis are investigated, further highlighting the essential enthalpy contributions to thermophoresis. Our work indicates that surface grafting would be important in designing high-efficiency thermally driven nanorobotic systems for biomedical applications.

Integrated multi-omics analyses reveal Jorunnamycin A as a novel suppressor for muscle-invasive bladder cancer by targeting FASN and TOP1.

BACKGROUND: Bladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied. METHODS: To examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed. RESULTS: JorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 µM, respectively. JorA-induced significantly changed proteins were enriched in "cancer-related pathways" and "EGFR-related signaling pathways", which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were - 8.153 and - 7.264 kcal/mol, respectively). CONCLUSIONS: The marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy.

Susceptibility of Eucalyptus trees to defoliation by the Eucalyptus snout beetle, Gonipterus sp. n. 2, is enhanced by high foliar contents of 1,8-cineole, oxalic acid and sucrose and low contents of palmitic and shikimic acid.

Gonipterus sp. n. 2 (Coleoptera, Curculionidae) is an invasive, commercially important weevil that causes large-scale defoliation of Eucalyptus trees. The weevil specifically feeds on young leaves and new shoots, thus reducing tree growth. The weevil displays a very strong preference for certain Eucalyptus genotypes, however, this behaviour and the chemistry underlying it is poorly understood, thereby complicating the selection of resistant trees. To elucidate the feeding preference of Gonipterus sp. n. 2, we assessed the relative levels of susceptibility of 62 Eucalyptus genotypes from 23 species using a laboratory choice assay. This revealed large intraspecific variation in susceptibility to weevil feeding, which for certain species, exceeded the interspecific variation. A semiquantitative metabolite profile analysis on 13 genotypes revealed strong correlations of 10 metabolites to feeding damage. The behavioural effects of the identified compounds were assessed through an in vitro feeding preference assay using artificial diets as well as under field conditions. This revealed three phagostimulants (1,8-cineole, oxalic acid and sucrose) and two feeding deterrent compounds (shikimic acid and palmitic acid) for Gonipterus sp. n. 2. These chemical markers can be applied to tree breeding programmes for the selection of resistant genotypes to reduce damage caused by Gonipterus weevils.

Differences in rectal amino acid levels determine bacteria-originated sex pheromone specificity in two closely related flies.

Sex pheromones are widely used by insects as a reproductive isolating mechanism to attract conspecifics and repel heterospecifics. Although researchers have obtained extensive knowledge about sex pheromones, little is known about the differentiation mechanism of sex pheromones in closely related species. Using Bactrocera dorsalis and Bactrocera cucurbitae as the study model, we investigated how the male-borne sex pheromones are different. The results demonstrated that both 2,3,5-trimethylpyrazine (TMP) and 2,3,5,6-tetramethylpyrazine (TTMP) were sex pheromones produced by rectal Bacillus in the two flies. However, the TMP/TTMP ratios were reversed, indicating sex pheromone specificity in the two flies. Bacterial fermentation results showed that different threonine and glycine levels were responsible for the preference of rectal Bacillus to produce TMP or TTMP. Accordingly, threonine (glycine) levels and the expression of the threonine and glycine coding genes were significantly different between B. dorsalis and B. cucurbitae. In vivo assays confirmed that increased rectal glycine and threonine levels by amino acid feeding could significantly decrease the TMP/TTMP ratios and result in significantly decreased mating abilities in the studied flies. Meanwhile, decreased rectal glycine and threonine levels due to RNAi of the glycine and threonine coding genes was found to significantly increase the TMP/TTMP ratios and result in significantly decreased mating abilities. The study contributes to the new insight that insects and their symbionts can jointly regulate sex pheromone specificity in insects, and in turn, this helps us to better understand how the evolution of chemical communication affects speciation.