High-performance peptide biosensor based on unified structure of lotus silk.

The sensitive materials of current gas sensors are fabricated on planar substrates, significantly limiting the quantity of sensitive material available on the sensor and the complete exposure of the sensitive material to the target gas. In this work, we harnessed the finest, resilient, naturally degradable, and low-cost lotus silk derived from plant fibers, to fabricate a high-performance bio-sensor for toxic and harmful gas detection, employing peptides with full surface connectivity. The proposed approach to fabricate gas sensors eliminated the need for substrates and electrodes. To ascertain the effectiveness and versatility of the sensors created via this method, sensors for three distinct representative gases (isoamyl alcohol, 4-vinylanisole, and benzene) were prepared and characterized. These sensors surpassed reported detection limits by at least one order of magnitude. The inherent pliancy of lotus silk imparts adaptability to the sensor architecture, facilitating the realization of 1D, 2D, or 3D configurations, all while upholding consistent performance characteristics. This innovative sensor paradigm, grounded in lotus silk, represents great potential toward the advancement of highly proficient bio gas sensors and associated applications.

Lithium Niobate Electro-Optic Modulation Device without an Overlay Layer Based on Bound States in the Continuum.

Electro-optic modulation devices are essential components in the field of integrated optical chips. High-speed, low-loss electro-optic modulation devices represent a key focus for future developments in integrated optical chip technology, and they have seen significant advancements in both commercial and laboratory settings in recent years. Current electro-optic modulation devices typically employ architectures based on thin-film lithium niobate (TFLN), traveling-wave electrodes, and impedance-matching layers, which still suffer from transmission losses and overall design limitations. In this paper, we demonstrate a lithium niobate electro-optic modulation device based on bound states in the continuum, featuring a non-overlay structure. This device exhibits a transmission loss of approximately 1.3 dB/cm, a modulation bandwidth of up to 9.2 GHz, and a minimum half-wave voltage of only 3.3 V.

Construction and validation of infection risk model for patients with external ventricular drainage: a multicenter retrospective study.

PURPOSE: External ventricular drainage (EVD) is a life-saving neurosurgical procedure, of which the most concerning complication is EVD-related infection (ERI). We aimed to construct and validate an ERI risk model and establish a monographic chart. METHODS: We retrospectively analyzed the adult EVD patients in four medical centers and split the data into a training and a validation set. We selected features via single-factor logistic regression and trained the ERI risk model using multi-factor logistic regression. We further evaluated the model discrimination, calibration, and clinical usefulness, with internal and external validation to assess the reproducibility and generalizability. We finally visualized the model as a nomogram and created an online calculator (dynamic nomogram). RESULTS: Our research enrolled 439 EVD patients and found 75 cases (17.1%) had ERI. Diabetes, drainage duration, site leakage, and other infections were independent risk factors that we used to fit the ERI risk model. The area under the receiver operating characteristic curve (AUC) and the Brier score of the model were 0.758 and 0.118, and these indicators' values were similar when internally validated. In external validation, the model discrimination had a moderate decline, of which the AUC was 0.720. However, the Brier score was 0.114, suggesting no degradation in overall performance. Spiegelhalter's Z-test indicated that the model had adequate calibration when validated internally or externally (P = 0.464 vs. P = 0.612). The model was transformed into a nomogram with an online calculator built, which is available through the website: https://wang-cdutcm.shinyapps.io/DynNomapp/ . CONCLUSIONS: The present study developed an infection risk model for EVD patients, which is freely accessible and may serve as a simple decision tool in the clinic.

Microwave photonic radar system with improved SNR performance utilizing optical resonant amplification and random Fourier coefficient waveforms.

A microwave photonic (MWP) radar system with improved signal-to-noise ratio (SNR) performance is proposed and experimentally demonstrated. By improving the SNR of echoes through properly designed radar waveforms and resonant amplification in the optical domain, the proposed radar system can detect and image weak targets that were previously hidden in noise. Echoes with a common low-level SNR obtain high optical gain and the in-band noise is suppressed during resonant amplification. The designed radar waveforms, based on random Fourier coefficients, reduce the effect of optical nonlinearity while providing reconfigurable waveform performance parameters for different scenarios. A series of experiments are developed to verify the feasibility of the SNR improvement of the proposed system. Experimental results show a maximum SNR improvement of 3.6 dB with an optical gain of 28.6 dB for the proposed waveforms over a wide input SNR range. From a comparison with linear frequency modulated signals in microwave imaging of rotating targets, significant quality enhancement is observed. The results confirm the ability of the proposed system to improve SNR performance of MWP radars and its great application potential in SNR-sensitive scenarios.

Susceptibility of Hyphantria cunea larvae to Beauveria bassiana under Cd Stress: An integrated study of innate immunity and energy metabolism.

Biological control is widely used for integrated pest management. However, there are many abiotic factors that can affect the biocontrol efficiency. In this study, we investigated the susceptibility of Hyphantria cunea larvae to Beauveria bassiana under Cd stress, and the corresponding mechanism was analyzed around innate immunity and energy metabolism. The results showed that mortality of H. cunea larvae treated with Cd and B. bassiana was significantly higher than those treated with B. bassiana alone, and the combined lethal effect exhibited a synergistic effect. Compared with the single fungal treatment group, the total hemocyte count in the combined Cd and fungal treatment group decreased significantly, accompanied by a decrease in phagocytosis, encapsulation, and melanization activity. The expression levels of three phagocytosis-related genes, one encapsulation-promoting gene, and one melanization-regulating gene were significantly lower in the combined treatment group than those in the single fungal treatment group. Furthermore, pathogen recognition ability, signal transduction level, and immune effector expression level were weaker in the combined treatment group than those in the single fungal treatment group. The expression levels of 14 key metabolites and 7 key regulatory genes in glycolysis and tricarboxylic acid cycle pathways were significantly lower in the combined treatment group than those in the single fungal treatment group. Taken together, the weakness of innate immunity and energy metabolism in response to pathogen infection resulted in an increased susceptibility of H. cunea larvae to B. bassiana under Cd pre-exposure. Microbial insecticide is a preferred strategy for pest control in heavy metal-polluted areas. AVAILABILITY OF DATA AND MATERIAL: All the data that support the findings of this study are available in the manuscript.

Miniature Fourier Transform Spectrometer Based on Thin-Film Lithium Niobate.

A miniature Fourier transform spectrometer is proposed using a thin-film lithium niobate electro-optical modulator instead of the conventional modulator made by titanium diffusion in lithium niobate. The modulator was fabricated by a contact lithography process, and its voltage-length and optical waveguide loss were 2.26 V·cm and 1.01 dB/cm, respectively. Based on the wavelength dispersion of the half-wave voltage of the fabricated modulator, the emission spectrum of the input signal was retrieved by Fourier transform processing of the interferogram, and the analysis of the experimental data of monochromatic light shows that the proposed miniaturized FTS can effectively identify the input signal wavelength.

Low-loss, ultracompact n-adjustable waveguide bends for photonic integrated circuits.

Countless waveguides have been designed based on four basic bends: circular bend, sine/cosine bend, Euler bend (developed in 1744) and Bezier bend (developed in 1962). This paper proposes an n-adjustable (NA) bend, which has superior properties compared to other basic bends. Simulations and experiments indicate that the NA bends can show lower losses than other basic bends by adjusting n values. The circular bend and Euler bend are special cases of the proposed NA bend as n equals 0 and 1, respectively. The proposed bend are promising candidates for low-loss compact photonic integrated circuits.

Sex Pheromone Receptor-Derived Peptide Biosensor for Efficient Monitoring of the Cotton Bollworm Helicoverpa armigera.

The cotton bollworm, Helicoverpa armigera (H. armigera), causes damage to a wide range of cultivated crops and is one of the pests with the greatest economic importance for global agriculture. Currently, the detection of H. armigera is based on manual sampling. A low limit of detection (LOD), convenient, and real-time monitoring method is urgently needed for its early warning and efficient management. Here, we characterized the amino acid sequence in the sex pheromone receptors (SPRs) recognizing the pheromone components of H. armigera by three-dimensional (3D) modeling and molecular docking. Next, sex pheromone receptor-derived peptides (SPRPs) were synthesized and conjugated to nanotubes by chemical connection. The modified nanotubes were used to fabricate a sensor capable of real-time monitoring of gaseous sex pheromone compounds with a low LOD (∼10 ppb for Z11-16:Ald) and selectivity, and the sensor was able to detect a single live H. armigera. Furthermore, the developed biosensor allowed direct monitoring of the pheromone release dynamics by female H. armigera and showed that the release was instantly reduced in response to light. Here, we report the first demonstration of a biosensing method for detecting gaseous sex pheromones and live H. armigera. The findings show the great potential of the SPRP sensor for broad applications in insect biology study and infestation monitoring.

Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling.

BACKGROUND: PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated. METHODS: By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes. RESULTS: PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell-cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs. CONCLUSIONS: Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.

Ultrasensitive Flexible Olfactory Receptor-Derived Peptide Sensor for Trimethylamine Detection by the Bending Connection Method.

Trimethylamine (TMA) is a harmful gas that exists ubiquitously in the environment; therefore, the sensitive and specific monitoring of TMA is necessary. In this work, we prepared ultrasensitive flexible sensors for TMA detection based on single-walled carbon nanotubes (SWCNTs) and olfactory receptor-derived peptides (ORPs) on low-cost plastic substrates. A novel bending connection method was developed by intentionally bending the interdigitated electrodes with SWCNTs to form a three-dimensional structure during the ORP-connection process, leading to the exposure of more modification sites. The method showed ∼4.7-fold more effective connection amount of the ORPs to SWCNTs compared to the conventional flat-condition connection method. The flexible ORP-SWCNT sensors could significantly improve the limit of detection for gaseous TMA from the reported lowest limit of 10 parts per quadrillion (ppq) to 0.1 ppq. The flexible ORP sensors also exhibited excellent sensitivity to vaporized TMA standards and TMA generated by different kinds of foods under different bending conditions. The results showed that the bending connection method in this work was effective for ultrasensitive flexible ORP sensors and their associated applications.

Investigation of signal-to-noise ratio performance of microwave photonic links enhanced by optical injection locking and channelized spectrum stitching.

A signal-to-noise ratio (SNR) improvement method for microwave photonic (MWP) links enhanced by optical injection locking (OIL) and channelized spectrum stitching (CSS) is investigated and experimentally demonstrated. By exploiting the resonant amplification characteristics of OIL, both optical gain and in-band noise suppression of the input radio frequency signal can be achieved. The injection bandwidth is channelized to further suppress noise during OIL, and the input signal can be well reconstructed by spectrum stitching in the digital domain. Experimental results show that the optimal improvement in SNR of 3.6 dB is achieved for linear frequency modulated signals and at least an additional improvement of 7.2 dB can be obtained by adopting CSS. Other broadband signals for radar and communication are used to further verify the ability to improve SNR. The potential for application scenarios with large operating bandwidth and high optical gain is also demonstrated.

Kynurenine produced by tryptophan 2,3-dioxygenase metabolism promotes glioma progression through an aryl hydrocarbon receptor-dependent signaling pathway.

The current studies associated with tumor biology continue to describe a high correlation between tryptophan (Trp) metabolism and tumor progression. These findings reflect the complex underlying mechanism of tumor development and highlight the need to explore additional drug targets for carcinoma-associated diseases. In our study, we reported that elevated Trp metabolism was observed in highly malignant glioma tumor tissues from patients. The elevated Trp metabolism in glioma cells were induced by the overexpression of Trp 2,3-dioxygenase 2 (TDO2), which further contributed to the production of the metabolite kynurenine (Kyn). Subsequently, the Kyn derived from Trp metabolism was able to mediate the activation of the aryl hydrocarbon receptor (AhR) and downstream PI3K/AKT signals, resulting in the strengthening of tumor stemness and growth. Meanwhile, the activation of the AhR could promote the process of epithelial-mesenchymal transition in gliomas through a TGF-ß-dependent mechanism, leading to enhanced tumor invasion in vitro and in vivo. Inhibition of the AhR using StemRegenin 1 was demonstrated to suppress glioma growth and improve the outcome of traditional chemotherapy in subcutaneous tumor-bearing mice, representing a promising therapeutic target for clinical glioma treatment.

ATP is not essential for cadaverine production by Escherichia coli whole-cell bioconversion.

ATP plays an essential role in the substrate/product transmembrane transportation during whole-cell bioconversion. This study aimed to address the impact of ATP upon cadaverine synthesis by whole-cell biocatalysts. The results showed no significant change in the ATP content (P = 0.625), and the specific cadaverine yield (P = 0.374) was observed in enzyme-catalyzed cadaverine synthesis with exogenous addition of ATP, indicating that the enzyme-catalyzed process does not require the participation of ATP. Furthermore, a whole-cell biocatalyst co-overexpressed methionine adenosyltransferase (MetK), lysine decarboxylase (CadA), and lysine/cadaverine antiporter (CadB) was constructed and used to investigate the effect of ATP deficiency on the cadaverine production by conversion of L-methionine and L-lysine, simultaneously. The results showed no significant difference (P = 0.585) in the specific cadaverine content between high and low levels of intracellular ATP. In addition, the intra- and extracellular cadaverine concentration and the ratio of ATP/ADP of whole-cell biocatalyst were determined. Results showed that the extracellular cadaverine concentration was much higher than the intracellular concentration, and no significant changes in ATP/ADP ratio during cadaverine synthesis. In contrast, an inhibition effect of the proton motive force (PMF) inhibitor carbonyl cyanide m-chlorophenylhydrazone (CCCP) on cadaverine production was detected. These findings strongly suggest that cadaverine transport in whole-cell biocatalysts was energized by PMF rather than ATP. Finally, a model was proposed to describe cadaverine's PMF-driven transport under different external pHs during whole-cell biocatalysis. This study is the first to experimentally confirm that the cadaverine production by Escherichia coli whole-cell bioconversion is independent of intracellular ATP, which helps guide the subsequent construction of biocatalysts and optimize transformation conditions.

High-performance olfactory receptor-derived peptide sensor for trimethylamine detection based on Steglich esterification reaction and native chemical ligation connection.

Trimethylamine (TMA) commonly exists in daily life and is harmful to human health, therefore the convenient and sensitive monitoring of TMA is highly desired. In this study, we developed a method to fabricate a high-performance TMA sensor by chemically conjugating olfactory receptor-derived peptides (ORPs) to single-walled carbon nanotubes (SWCNTs) on interdigital electrodes. First, the SWCNTs were modified with thioester by Steglich esterification reaction. Next, the ORPs with a cysteine residue at the N-terminus were connected to the thioester by native chemical ligation and modified to the surface of the SWCNTs. The chemical connection method enabled more effective loading of ORPs to the SWCNTs compared to the previously reported physical connection method. Using this approach, the ORPs-SWCNTs sensor for gaseous TMA was fabricated and enabled detection of TMA with a concentration as low as 0.01 parts per trillion, which was three orders of magnitude lower than the reported lowest detection limit up to date. Furthermore, we tested the performance of the ORP-sensor with vaporized TMA and TMA generated from various spoiled food, and the sensor exhibited excellent sensitivity, selectivity, and stability for TMA detection. The results demonstrated the effectiveness of the proposed chemical connection method for the fabrication of ORP-sensor and the great potential of using these sensors for applications in environmental safety, food quality evaluation, and healthcare.

Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 µM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 µM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

Screening of gamma-aminobutyric acid-producing lactic acid bacteria and its application in Monascus-fermented rice production.

BACKGROUND: Gamma-aminobutyric acid (GABA), with an antidepressant effect, and Monacolin K, with a cholesterol-lowering effect, are the main bioactive ingredients in Monascus-fermented rice (MFR). The simultaneous enrichment of both ingredients can effectively enhance the health benefits of MFR. However, the capacity of Monascus spp. to produce GABA is limited. METHODS: Seventeen lactic acid bacteria (LAB) strains were preliminarily screened for GABA-producing by whole-cells bioconversion of L-glutamate, followed by rescreening through fermentation with the addition of the precursor L-glutamic acid. Subsequently, the bioconversion conditions (temperature, metal ions, and pH) for the conversion of L-monosodium glutamate (MSG) were investigated. Additionally, the GABA-producing LAB was co-inoculated with a monacolin K producing strain Monascus anka 20-2, and the ratio of M. anka 20-2 to LAB in microbial consortia was optimized for MFR production. RESULTS: The strain Lactobacillus plantarum 8014 was screened out for its ability to produce GABA. At an optimal temperature of 33°C and pH 7.5, with the addition of 0.05 g/L ZnSO4, the strain showed an L-glutamate conversion rate of 100%. The ratio optimization of M. anka 20-2 to L. plantarum 8014 in microbial consortia showed that when the dry cell ratio was 2:1, the content of monacolin K and GABA in the MFR simultaneously reached 2.22 mg/g and 29.9 mg/g, respectively. CONCLUSIONS: A two-stage fermentation using microbial consortia containing M. anka 20-2 and L. plantarum 8014 was developed for the production of bioactive MFR, in which the active ingredients monacolin K and GABA were simultaneously enriched, with good consumer acceptability due to the aromatic scent produced by lactic acid bacteria.

Practical two-dimensional beam steering system using an integrated tunable laser and an optical phased array.

A practical two-dimensional beam steering solid-state system based on the synthesis of one-dimensional wavelength tuning and a one-dimensional optical phased array is demonstrated and investigated. The system incorporates an integrated multiple-channel-interference widely tunable laser, an integrated 32-channel optical phased array, an offline phase error correction unit, and home-made control electronics. The introduction of the integrated tunable laser avoids the traditional bulky light source fed into the optical phased array, making the architecture promising to be miniaturized. In addition, a calibration method based on particle swarm optimization is proposed and proved to be effective to correct the phase errors existing in the arrayed channels and improve the emitted far-field quality. Other practical aspects, such as high-speed control and cost, are taken into the consideration of the system design as well. Under the control of home-made electronics, the laser exhibits a tuning range of 50 nm with a 44 dB side-mode suppression ratio, and the system presents the characteristics of low divergence (0.63∘×0.58∘), high side-lobe suppression ratio (>10dB), and high-speed response (<10µs time constant) in an aliasing-free sweeping range of 18∘×7∘.

Hyperprolactinemia in clinical non-functional pituitary macroadenomas: A STROBE-compliant study.

Hyperprolactinemia is a prevalent endocrine disorder presented in patients with non-functional pituitary adenomas (NFPAs). However, the mechanism involved in hyperprolactinemia in NFPA is not fully illustrated. The current study aims to investigate predictors for hyperprolactinemia in NFPA via analyzing relevant clinical features. Thus, in this study, a cohort of 214 cases with integrated medical records was retrospectively analyzed concerning clinical, pathological, and endocrinological studies before and after surgery.Hyperprolactinemia happened in 93 cases (43.5%). Women (adjust odds ratio [OR] = 3.093; P < .01), age of patients (adjust OR = 0.951; P < .01), and serum free tetraiodothyronine (FT4) level (adjust OR = 0.882; P = .02) were independent predictors for developing preoperative hyperprolactinemia. Tumor size and hypopituitarism had no impact on hyperprolactinemia. During a median follow-up of 43.5 (range, 22-80) months, 83.9% patients with preoperative hyperprolactinemia experienced prolactin (PRL) normalization. Preoperative PRL level (adjusted OR = 1.741, P = .03) was the exclusive predictor for PRL normalization after adjusting for tumor volume, preoperative serum FT4 concentration, and postoperative residual. The PRL normalization rate of patients with lower PRL level (<2.35-fold upper limit of normal range) was 95.2% and decreased to 65.5% for patients with higher PRL level.In conclusion, our results suggest existence of potentially alternative mechanisms underlying hyperprolactinemia in NFPAs, like the discrepancy of sex and age and the negative feedback of FT4. Preoperative PRL is a predictor for postoperative PRL normalization, which is of clinically relevant for postoperative management of NFPAs.

Proliferation, Differentiation and Immunoregulatory Capacities of Brown and White Adipose-Derived Stem Cells from Young and Aged Mice.

BACKGROUND AND OBJECTIVES: Adipose tissue is a source of mesenchymal stem cells, which have the potential to differentiate into various types of cells. Adipose-derived stem cells (ADSCs) are now recognized as an accessible, abundant, and reliable stem cells suitable for tissue engineering and regenerative medicine applications. However, few literatures gave a comprehensive report on the capacities of ADSCs harvested from different sites. Especially, the capacities of ADSCs from aged mice remained unclear. In this study, we investigated several main capacities of brown adipose derived stem cells (B-ADSCs) and white adipose derived stem cells (W-ADSCs) from both young and aged mice. METHODS AND RESULTS: When isolated from young mice, B-ADSCs showed a stronger proliferation rate and higher osteogenic, adipogenic and myocardial differentiation ability than W-ADSCs. Carboxy fluorescein diacetate succinimidyl ester (CFSE) labeling test suggested no significant difference in immunosuppression capacity between B-ADSCs and W-ADSCs. Similarly, no difference between these two were found in several immune related molecules, such as programmed death-ligand 1 (PD-L1), intercellular cell adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), interleukin 10 (IL10), and suppressor of cytokine signaling 1 (socs1). When isolated from aged mice, B-ADSCs also showed a stronger proliferation rate and higher osteogenic, adipogenic and myocardial differentiation ability than W-ADSCs; however, it demonstrated an attenuated immunosuppression capacity compared to W-ADSCs. CONCLUSIONS: In summary, our data showed that ADSCs' characteristics were tissue source dependent and changed with age. It provided evidence for choosing the right tissue-specific ADSCs for clinical application and fundamental research.