TFEB safeguards trophoblast syncytialization in humans and mice.

Nutrient sensing and adaptation in the placenta are essential for pregnancy viability and proper fetal growth. Our recent study demonstrated that the placenta adapts to nutrient insufficiency through mechanistic target of rapamycin (mTOR) inhibition-mediated trophoblast differentiation toward syncytiotrophoblasts (STBs), a highly specialized multinucleated trophoblast subtype mediating extensive maternal-fetal interactions. However, the underlying mechanism remains elusive. Here, we unravel the indispensable role of the mTORC1 downstream transcriptional factor TFEB in STB formation both in vitro and in vivo. TFEB deficiency significantly impaired STB differentiation in human trophoblasts and placenta organoids. Consistently, systemic or trophoblast-specific deletion of Tfeb compromised STB formation and placental vascular construction, leading to severe embryonic lethality. Mechanistically, TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 in human trophoblasts and thereby promoted STB formation, independent of its canonical function as a master regulator of the autophagy-lysosomal pathway. Moreover, we demonstrated that TFEB directed the trophoblast syncytialization response driven by mTOR complex 1 (mTORC1) signaling. TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth-restricted placentas exhibiting suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis ensures proper STB formation during placenta development and under nutrient stress, shedding light on TFEB as a mechanistic link between nutrient-sensing machinery and trophoblast differentiation.

Facile Transformation from Rofecoxib to a New Near-Infrared Lipid Droplet Fluorescent Probe and Its Investigations on AIE Property, Solvatochromism and Mechanochromism.

Lipid-related cancers cause a large number of deaths worldwide. Therefore, development of highly efficient Lipid droplets (LDs) fluorescent imaging probes will be beneficial to our understanding of lipid-related cancers by allowing us to track the metabolic process of LDs. In this work, a LDs-specific NIR (λmax = 698 nm) probe, namely BY1, was rationally designed and synthesized via a one-step reaction by integrating triphenylamine (electron-donor group) unit into the structure of rofecoxib. This integration strategy enabled the target BY1 to form a strong Donor-Acceptor (D-A) system and endowed BY1 with obvious aggregation-induced emission (AIE) effect. Meanwhile, BY1 also showed observable solvent effect and reversible mechanochromatic luminescent property, which could be interpreted clearly via density functional theory (DFT) calculations, differential scanning calorimetry (DSC), powder X-ray diffraction (XPRD), and single crystal X-ray data analysis. More importantly, BY1 exhibited highly specific fluorescent imaging ability (Pearson's correlation = 0.97) towards lipid droplets in living HeLa cells with low cytotoxicity. These results demonstrated that BY1 is a new promising fluorescent probe for lipid droplets imaging, and it might be beneficial to facilitate biological research of lipid-related cancers.

Unified Accurate Attitude Control for Dual-Tiltrotor UAV with Cyclic Pitch Using Actuator Dynamics Compensated LADRC.

This paper proposes a unified attitude controller based on the modified linear active disturbance rejection control (LADRC) for a dual-tiltrotor unmanned aerial vehicle (UAV) with cyclic pitch to achieve accurate attitude control despite its nonlinear and time-varying characteristics during flight mode transitions. The proposed control algorithm has higher robustness against model mismatch compared with the model-based control algorithms. The modified LADRC utilizes the state feedbacks from the onboard sensors like IMU and Pitot tube instead of the mathematical model of the plane. It has less dependency on the accurate dynamics model of the dual-tiltrotor UAV, which can hardly be built. In contrast to the original LADRC, an actuator model is integrated into the modified LADRC to compensate for the non-negligible slow rotor flapping dynamics and servo dynamics. This modification eliminates the oscillation of the original LADRC when applied on the plant with slow-response actuators, such as propeller and rotors of the helicopter. In this way, the stability and performance of the controller are improved. The controller replaces the gain-scheduling or the control logic switching by a unified controller structure, which simplifies the design approach of the controller for different flight modes. The effectiveness of the modified LADRC and the performance of the unified attitude controller are demonstrated in both simulation and flight tests using a dual-tiltrotor UAV. The attitude control error is less than ±4° during the conversion flight. The control rising time in different flight modes is all about 0.5 s, despite the variations in the airspeed and tilt angle. The flight results show that the controller guarantees high control accuracy and uniform control quality in different flight modes.

Achieving Molecular Fluorescent Conversion from Aggregation-Caused Quenching to Aggregation-Induced Emission by Positional Isomerization.

In this work, we synthesized a pair of positional isomers by attaching a small electron-donating pyrrolidinyl group at ortho- and para-positions of a conjugated core. These isomers exhibited totally different fluorescent properties. PDB2 exhibited obvious aggregation-induced emission properties. In contrast, PDB4 showed the traditional aggregation-caused quenching effect. Their different fluorescent properties were investigated by absorption spectroscopy, fluorescence spectroscopy, density functional theory calculations and single-crystal structural analysis. These results indicated that the substituent position of the pyrrolidinyl groups affects the twisted degree of the isomers, which further induces different molecular packing modes, thus resulting in different fluorescent properties of these two isomers. This molecular design concept provided a new accurate strategy for designing new aggregation-induced emission luminogens.

Technical progress in circulating tumor DNA analysis using next generation sequencing.

Circulating tumor DNA (ctDNA) is tumor-derived, fragmented DNA that circulates freely in body fluids, predominantly in the peripheral blood. Recently, ctDNA analysis has been suggested as a complement to tissue biopsy in the detection and treatment of cancer. Genetic and epigenetic information specific to tumor cells, including single nucleotide variations, copy number variations, and modified methylation patterns, can be detected in ctDNA. Importantly, mutations in heterogenous tumors that could impart therapeutic resistance could be identified in ctDNA, which would aid in cancer diagnosis, prognosis, and real-time monitoring, and inform treatment with targeted therapies. However, ctDNA is still not a routinely used method for this purpose, because its detection techniques lack adequate sensitivity for reliable use in scientific studies and clinical trials. This review provides an up-to-date summary of ctDNA mutation detection methods based on next generation sequencing, highlighting their advantages and limitations, and focusing in particular on several optimized library preparation methods for improved sensitivity and specificity of ctDNA detection.

Analysis of genome-wide in cell free DNA methylation: progress and prospect.

DNA methylation is an important epigenetic marker that affects gene expression. Cell-free DNA methylation detection is a promising approach as abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. This review summarizes the existing literature and reviews on the detection methods based on next generation sequencing for DNA methylation. The review also discusses the feasibility of detecting cfDNA methylation and the latest progress.

Sub-200 fs soliton mode-locked fiber laser based on bismuthene saturable absorber.

Few-layer bismuthene is an emerging two-dimensional material in the fields of physics, chemistry, and material science. However, its nonlinear optical property and the related photonics device have been seldom studied so far. Here, we demonstrate a sub-200 fs soliton mode-locked erbium-doped fiber laser (EDFL) using a microfiber-based bismuthene saturable absorber for the first time, to the best of our knowledge. The bismuthene nanosheets are synthesized by the sonochemical exfoliation method and transferred onto the taper region of a microfiber by the optical deposition method. Stable soliton pulses centered at 1561 nm with the shortest pulse duration of about 193 fs were obtained. Our findings unambiguously imply that apart from its fantastic electric and thermal properties, few-layer bismuthene may also possess attractive optoelectronic properties for nonlinear photonics, such as mode-lockers, Q-switchers, optical modulators and so on.

Research on the chemical oxygen demand spectral inversion model in water based on IPLS-GAN-SVM hybrid algorithm.

Spectral collinearity and limited spectral datasets are the problems influencing Chemical Oxygen Demand (COD) modeling. To address the first problem and obtain optimal modeling range, the spectra are preprocessed using six methods including Standard Normal Variate, Savitzky-Golay Smoothing Filtering (SG) etc. Subsequently, the 190-350 nm spectral range is divided into 10 subintervals, and Interval Partial Least Squares (IPLS) is used to perform PLS modeling on each interval. The results indicate that it is best modeled in the 7th range (238~253 nm). The values of Mean Square Error (MSE), Mean Absolute Error (MAE) and R2score of the model without pretreatment are 1.6489, 1.0661, and 0.9942. After pretreatment, the SG is better than others, with MSE and MAE decreasing to 1.4727, 1.0318 and R2score improving to 0.9944. Using the optimal model, the predicted COD for three samples are 10.87 mg/L, 14.88 mg/L, and 19.29 mg/L. To address the problem of the small dataset, using Generative Adversarial Networks for data augmentation, three datasets are obtained for Support Vector Machine (SVM) modeling. The results indicate that, compared to the original dataset, the SVM's MSE and MAE have decreased, while its accuracy has improved by 2.88%, 11.53%, and 11.53%, and the R2score has improved by 18.07%, 17.40%, and 18.74%.

Design and implementation of a Li River water quality monitoring and analysis system based on outlier data analysis.

The detection of water quality indicators such as Temperature, pH, Turbidity, Conductivity, and TDS involves five national standard methods. Chemically based measurement techniques may generate liquid residue, causing secondary pollution. The water quality monitoring and data analysis system can effectively address the issues that conventional methods require multiple pieces of equipment and repeated measurements. This paper analyzes the distribution characteristics of the historical data from five sensors at a specific time, displays them graphically in real time, and provides an early warning of exceeding the standard; It selects four water samples from different sections of the Li River, based on the national standard method, the average measurement errors of Temperature, PH, TDS, Conductivity and Turbidity are 0.98%, 2.23%, 2.92%, 3.05% and 3.98%.;It further uses the quartile method to analyze the outlier data over 100,000 records and five historical periods are selected. Experiment results show the system is relatively stable in measuring Temperature, PH and TDS, and the proportion of outlier is 0.42%, 0.84% and 1.24%. When Turbidity and Conductivity are measured, the proportion is 3.11% and 2.92%. In the experiment of using 7 methods to fill outlier, K nearest neighbor algorithm is better than others. The analysis of data trends, outliers, means, and extreme values assists in making decisions, such as updating and maintaining equipment, addressing extreme water quality situations, and enhancing regional water quality oversight.

Application of Bioinformatics in Predicting the Efficacy of Digestive Tumour Immunotherapy Target TIM-3 and its Inhibitors.

Background: Our main objective is to apply bioinformatics in predicting the efficacy of digestive tumour immunotherapy target TIM-3 and its inhibitors. Methods: Our study used the gene expression omnibus (GEO) database to identify datasets associated with digestive tumours and the action of TIM-3. The GSE427729 dataset based on the GPL10192 platform. The dataset consisted of six samples of total RNA derived from TIM-3 control and knockdown RAW 264.7 cells. We used GEO2R tool to identify DEGs before performing Gene Ontology and identifying the kyoto encyclopedia of genes and genomes (KEGG) pathways. Lastly, we determined the PPI networks to identify hub genes. Results: Our study identified 57 differentially expressed genes based on an adjusted p-value of less than 0.05 and a log2 fold change of 2.0. There were 26 down-regulated genes with 31 up-regulated genes while 22, 404 genes were non-significant. The DEGs were enriched in biological pathways such as activating leukocytes, cells, and development of the immune system. Additionally, we identified four significant KEGG pathways that were implicated in digestive tumour immunotherapy and TIM-3; pathways of pancreatic cancer, NF-Kappa B signalling pathway, Toll-like receptor signalling pathway and C-type lectin receptor signalling pathway. The PPI networks identified 10 hub genes that were implicated in digestive tumour immunotherapy target TIM-3 (Myd88, Traf6, Irf7, Cdk4, Ccnd2, Mapkap1, Prr5, Mpp3, Serpinb6b and Pvrl3). Conclusion: Targeting these biological pathways, KEGG pathways, molecular functions and cellular processes can lead to novel therapeutic treatment and management in digestive tumours based on TIM-3 immunotherapy.

Sensing and Controlling Strategy for Upper Extremity Prosthetics Based on Piezoelectric Micromachined Ultrasound Transducer.

Surface electromyography (sEMG) is currently the primary method for user control of prosthetic manipulation. Its inherent limitations of low signal-to-noise ratio, limited specificity and susceptibility to noise, however, hinder successful implementation. Ultrasound provides a possible alternative, but current systems with medical probes are expense, bulky and non-wearable. This work proposes an innovative prosthetic control strategy based on a piezoelectric micromachined ultrasound transducer (PMUT) hardware system. Two PMUT-based probes were developed, comprising a 23×26 PMUT array and encapsulated in Ecoflex material. These compact and wearable probes represent a significant improvement over traditional ultrasound probes as they weigh only 1.8 grams and eliminate the need for ultrasound gel. A preliminary test of the probes was performed in non-disabled subjects performing 12 different hand gestures. The two probes were placed perpendicular to the flexor digitorum superficialis and brachioradialis muscles, respectively, to transmit/receive pulse-echo signals reflecting muscle activities. Hand gesture was correctly predicted 96% of the time with only these two probes. The adoption of the PMUT-based strategy greatly reduced the required number of channels, amount of processing circuit and subsequent analysis. The probes show promise for making prosthesis control more practical and economical.

High-Density Artificial Synapse Array Consisting of Homogeneous Electrolyte-Gated Transistors.

The artificial synapse array with an electrolyte-gated transistor (EGT) as an array unit presents considerable potential for neuromorphic computation. However, the integration of EGTs faces the drawback of the conflict between the polymer electrolytes and photo-lithography. This study presents a scheme based on a lateral-gate structure to realize high-density integration of EGTs and proposes the integration of 100 × 100 EGTs into a 2.5 × 2.5 cm2 glass, with a unit density of up to 1600 devices cm-2 . Furthermore, an electrolyte framework is developed to enhance the array performance, with ionic conductivity of up to 2.87 × 10-3  S cm-1 owing to the porosity of zeolitic imidazolate frameworks-67. The artificial synapse array realizes image processing functions, and exhibits high performance and homogeneity. The handwriting recognition accuracy of a representative device reaches 92.80%, with the standard deviation of all the devices being limited to 9.69%. The integrated array and its high performance demonstrate the feasibility of the scheme and provide a solid reference for the integration of EGTs.

Insights into the Correlation between Microbial Community Succession and Pericarp Degradation during Pepper (Piper nigrum L.) Peeling Process via Retting.

White pepper, used both as a seasoning in people's daily diets and as a medicinal herb, is typically produced by removing the pericarp of green pepper through the retting process. However, the mechanism of the retting process for peeling remains unclear. Therefore, this study aimed to investigate the changes in physicochemical factors, microbial community succession effects, and metabolites of the pepper pericarp during the pepper peeling process. The findings indicated that pre-treatment involving physical friction before the retting process effectively reduced the production time of white pepper. During the retting process, the pectinase activity increased, leading to a decrease in the pectin content in the pepper pericarp. There was a significant correlation observed between the changes in pH, pectin content, and peeling rate and the Shannon diversity index of bacteria and fungi. Prevotella, Lactococcus, and Candida were the dominant microbial genera during the retting. The functional predictions suggested that the monosaccharides degraded from the pepper pericarp could have been utilized by microbes through sugar metabolism pathways. Metabolomic analysis showed that the metabolic pathways of carbohydrates and amino acids were the main pathways altered during the pepper peeling process. The verification experiment demonstrated that the degradation of pectin into galacturonic acid by polygalacturonase was identified as the key enzyme in shortening the pepper peeling time. The structure of the pepper pericarp collapsed after losing the support of pectin, as revealed by scanning electron microscopy. These results suggest that the decomposition of the pepper pericarp was driven by key microbiota. The succession of microbial communities was influenced by the metabolites of the pepper pericarp during retting. These findings provide new insights into the retting process and serve as an important reference for the industrial production of white pepper.

Cytochrome P450 CitCYP97B modulates carotenoid accumulation diversity by hydroxylating ß-cryptoxanthin in Citrus.

Carotenoids in plant foods provide health benefits by functioning as provitamin A. One of the vital provitamin A carotenoids, ß-cryptoxanthin, is typically plentiful in citrus fruit. However, little is known about the genetic basis of ß-cryptoxanthin accumulation in citrus. Here, we performed a widely targeted metabolomic analysis of 65 major carotenoids and carotenoid derivatives to characterize carotenoid accumulation in Citrus and determine the taxonomic profile of ß-cryptoxanthin. We used data from 81 newly sequenced representative accessions and 69 previously sequenced Citrus cultivars to reveal the genetic basis of ß-cryptoxanthin accumulation through a genome-wide association study. We identified a causal gene, CitCYP97B, which encodes a cytochrome P450 protein whose substrate and metabolic pathways in land plants were undetermined. We subsequently demonstrated that CitCYP97B functions as a novel monooxygenase that specifically hydroxylates the ß-ring of ß-cryptoxanthin in a heterologous expression system. In planta experiments provided further evidence that CitCYP97B negatively regulates ß-cryptoxanthin content. Using the sequenced Citrus accessions, we found that two critical structural cis-element variations contribute to increased expression of CitCYP97B, thereby altering ß-cryptoxanthin accumulation in fruit. Hybridization/introgression appear to have contributed to the prevalence of two cis-element variations in different Citrus types during citrus evolution. Overall, these findings extend our understanding of the regulation and diversity of carotenoid metabolism in fruit crops and provide a genetic target for production of ß-cryptoxanthin-biofortified products.

DIEANet: an attention model for histopathological image grading of lung adenocarcinoma based on dimensional information embedding.

Efficient and rapid auxiliary diagnosis of different grades of lung adenocarcinoma is conducive to helping doctors accelerate individualized diagnosis and treatment processes, thus improving patient prognosis. Currently, there is often a problem of large intra-class differences and small inter-class differences between pathological images of lung adenocarcinoma tissues under different grades. If attention mechanisms such as Coordinate Attention (CA) are directly used for lung adenocarcinoma grading tasks, it is prone to excessive compression of feature information and overlooking the issue of information dependency within the same dimension. Therefore, we propose a Dimension Information Embedding Attention Network (DIEANet) for the task of lung adenocarcinoma grading. Specifically, we combine different pooling methods to automatically select local regions of key growth patterns such as lung adenocarcinoma cells, enhancing the model's focus on local information. Additionally, we employ an interactive fusion approach to concentrate feature information within the same dimension and across dimensions, thereby improving model performance. Extensive experiments have shown that under the condition of maintaining equal computational expenses, the accuracy of DIEANet with ResNet34 as the backbone reaches 88.19%, with an AUC of 96.61%, MCC of 81.71%, and Kappa of 81.16%. Compared to seven other attention mechanisms, it achieves state-of-the-art objective metrics. Additionally, it aligns more closely with the visual attention of pathology experts under subjective visual assessment.

Supershear triggering and cascading fault ruptures of the 2023 Kahramanmaras, Türkiye, earthquake doublet.

On 6 February 2023, two large earthquakes (moment magnitude 7.8 and 7.6) shocked a vast area of southeastern Türkiye and northern Syria, leading to heavy casualties and economic loss. To investigate the rupture process over multiple fault segments, we performed a comprehensive analysis of local seismic and geodetic data and determined supershear ruptures on the initial branch and the Pazarcik and Erkenek segments and subshear ruptures on the Amanos segment of event 1. The bilateral rupture of event 2 also presents distinct sub- and supershear velocities. The dynamic stress of the branch fault rupture triggered the Pazarcik segment initial rupture at a point 9 kilometers west of the junction of these two faults, boosting the supershear rupture of the Pazarcik segment of the main fault. The geometry and prestress level of multiple segments controlled the rupture behaviors and influenced the ground shaking intensity.

One-Step Transformations from ACQ Luminogens to DSEgens via the Boc Protection Process.

Dual-state emission luminogens (DSEgens), as a new type of luminescent materials that can effectively emit light in solution and solid state, have attracted tremendous attention due to their potential application in chemical sensing, biological imaging, organic electronic devices, etc. In this study, two new rofecoxib derivatives ROIN and ROIN-B have been synthesized, and their photophysical properties are fully investigated by experimental studies and theoretical calculations. The key intermediate ROIN, resulting from one-step conjugation of rofecoxib with an indole unit, shows the classical aggregation-caused quenching (ACQ) effect. Meanwhile, by introducing a tert-butoxycarbonyl (Boc) group on the basis of ROIN without enlarging the π conjugation system, ROIN-B was successfully developed with an obvious DSE property. In addition, both fluorescent behaviors and their transformation from ACQ to DSE were elucidated clearly by going through the analysis of their single X-ray data. Moreover, the target ROIN-B, as a new DSEgens, also displays reversible mechanofluorochromism and lipid droplet-specific imaging ability in HeLa cells. Taken together, this work proposes a precise molecular design strategy to afford a new DSEgens, which may provide guidance for the future exploration of new DSEgens.

Psychosocial interventions for suicidal and self-injurious-related behaviors among adolescents: a systematic review and meta-analysis of Chinese practices.

Background: Suicidal and self-injurious-related behaviors (SSIRBs) are a serious public health challenge in China. However, a comprehensive systematic review of psychosocial interventions for SSIRBs among Chinese adolescents has not been performed. To fill this gap, this systematic review and meta-analysis aimed to examine psychosocial interventions for SSIRBs among Chinese adolescents. Methods: Eight international (PubMed, EMBASE, Cochrane Library, ScienceDirect, Clinical Trial, CINAHL, PsycINFO, and Web of Science) and four Chinese (Wanfang, SinoMed, CEPS, and CNKI) databases were searched from inception to 31 January 2023. Data extraction and quality assessment were independently conducted by two groups of researchers. Qualitative synthesis and meta-analysis were both used. Results: The initial search yielded 16,872 titles. Of the 649 full texts reviewed, 19 intervention articles focusing on SSIRBs met the inclusion criteria. Thirteen out of the 19 included studies involved cognitive-behavioral therapy (CBT). Seven non-suicidal self-injury (NSSI) studies assessing self-injurious behaviors were included (six short-term studies and three long-term studies). Compared with long-term interventions [-1.30 (95% CI: -1.84, -0.76)], short-term psychosocial interventions had a higher standardized mean difference (SMD) value [1.86 (95% CI: -2.72, -0.99)]. Meta-regression showed an inverse relationship between the treatment response and sample size (slope = 0.068, Z = 2.914, p = 0.004) and proportion of females (slope = 1.096, Z = 5.848, p < 0.001). Subgroup analyses showed that compared with the "less than 1 month" group [-0.494 (-0.783, -0.205)], in the "immediate postintervention" group, the pooled estimate was significantly lower [-2.800 (-4.050, -1.550), p < 0.001]. Conclusion: Our review systematically summarized the key characteristics and effectiveness of existing psychosocial interventions for SSIRBs among Chinese adolescents. Short-term psychosocial interventions for NSSI were significantly effective in reducing self-injurious behavior scores, especially in the immediate postintervention period. More favorable treatment responses could be observed in both male and small samples.

Equivalence of LADRC and INDI controllers for improvement of LADRC in practical applications.

This paper explores the equivalence between the linear active disturbance rejection control (LADRC) and incremental nonlinear dynamic inversion (INDI) controllers. The equivalence is verified using an n-order, single-input-single-output, perturbed, pure integration plant which represents a class of feedback linearizable systems. And the linear extended state observer (LESO) inside the LADRC is interpreted from a filter perspective, which shows that the core of the LESO is a low-pass filter. A better parameter tuning method is proposed for the LESO. Then, based on the equivalence, an actuator model is integrated into the LADRC to improve its performance on the plant with non-negligible actuator dynamics that are ignored by the original LADRC. Through the modification, compared with the original LADRC, the bandwidth of the LESO and the whole controller is extended, so that improved performance can be achieved on the plants with low-bandwidth actuators. The equivalence between two controllers and the effectiveness of the improved LADRC are both demonstrated by experiments conducted on a quadrotor.

Simple and Effective: Spatial Rescaling for Person Reidentification.

Global average pooling (GAP) allows convolutional neural networks (CNNs) to localize discriminative information for recognition using only image-level labels. While GAP helps CNNs to attend to the most discriminative features of an object, e.g., head of a bird or one man's bag, it may suffer if that information is missing due to camera viewpoint changes and intraclass variations in some tasks. To circumvent this issue, we propose one new module to help CNNs to see more, namely, Spatial Rescaling (SpaRs) layer. It introduces spatial relations among the feature map activations back to the model, guiding the model to focus on a broad area in the feature map. With simple implementation, it can be inserted into CNNs of various architectures directly. SpaRs layer consistently improves the performance over the reidentification (re-ID) models. Besides, the new module based on different normalization methods also demonstrates the superiority of fine-grained and general image classification benchmarks. The visualization method shows the changes in activated regions when equipped with the SpaRs layer for better understanding. Our code is publicly available at https://github.com/HRanWang/Spatial-Re-Scaling.