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Abstract The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC.

Abstract Hydrogels capable of swift mechanical energy dissipation hold promise for a range of applications including impact protection, shock absorption, and enhanced damage resistance. Traditional energy absorption in such materials typically relies on viscoelastic mechanisms, involving sacrificial bond breakage, yet often suffers from prolonged recovery times. Here, we introduce a hydrogel designed for friction-based damping. This hydrogel features an internal structure that facilitates the motion of a chain walker within its network, effectively dissipating mechanical stress. The hydrogel network architecture allows for rapid restoration of its damping capacity, often within seconds, ensuring swift material recovery post-deformation. We further demonstrate that this hydrogel can significantly shield encapsulated cells from mechanical trauma under repetitive compression, owing to its proficient energy damping and rapid rebound characteristics. Therefore, this hydrogel has potential for dynamic load applications like artificial muscles and synthetic cartilage, expanding the use of hydrogel dampers in biomechanics and related areas.

Abstract Excitons in monolayer semiconductors, benefitting from their large binding energies, hold great potential towards excitonic circuits bridging nano-electronics and photonics. However, achieving room-temperature ultrafast on-chip electrical modulation of excitonic distribution and flow in monolayer semiconductors is nontrivial. Here, utilizing lateral bias, we report high-speed electrical modulation of the excitonic distribution in a monolayer semiconductor junction at room temperature. The alternating charge trapping/detrapping at the two monolayer/electrode interfaces induces a non-uniform carrier distribution, leading to controlled in-plane spatial variations of excitonic populations, and mimicking a bias-driven excitonic flow. This modulation increases with the bias amplitude and eventually saturates, relating to the energetic distribution of trap density of states. The switching time of the modulation is down to 5 ns, enabling high-speed excitonic devices. Our findings reveal the trap-assisted exciton engineering in monolayer semiconductors and offer great opportunities for future two-dimensional excitonic devices and circuits.

With increasing attention being paid to electric vehicles, hybrid braking systems combining regenerative braking and conventional friction braking have become a hot research topic. Although some important advancements have been achieved in the field of hybrid braking system control, these have not been fully summarized. In order to fill this gap and provide a comprehensive perspective for other researchers, this paper surveys a wide range of research works reported in the literature on hybrid braking system control. We identify the advantages and limitations of existing hybrid brake control strategies via comparative analysis. Through analysis, we find that the control strategy used for brake torque distribution and braking systems’ coordinated control in current hybrid braking systems are usually designed separately. In order to ensure braking stability, most of the current hybrid braking control strategies are designed relatively conservatively, and it is difficult to fully leverage the advantages of hybrid braking systems. Comprehensively considering the coordinated control of braking torque distribution and braking systems is a good research direction for hybrid braking control research. Overall, this survey summarizes the existing research relevant to hybrid brake control methods and also discusses the research challenges and new research directions.

Based on upper echelons theory and using a sample of private Chinese A-share listed firms from 2008 to 2020, this paper studies the impact of executives’ overseas experience on firms’ labor investment efficiency. The results show that executives with overseas experience significantly enhance firms’ labor investment efficiency. After distinguishing between different types of overseas experience, the results show that executives with only study experience or with both study and work experience abroad have a significant positive effect on firms’ labor investment efficiency, while executives with only overseas work experience have no significant effect. A cross-sectional analysis based on labor adjustment costs shows that the positive impact of executives’ overseas experience is more pronounced in labor-intensive firms, firms with a greater proportion of R&D investment and firms with a higher percentage of highly educated employees. The mechanism tests show that executives with overseas experience can optimize labor investment efficiency by lowering agency costs, attracting analyst attention and alleviating financing constraints under conditions of underemployment. This study enriches the literature on the characteristics of executive teams and the efficiency of labor investment, providing reference and inspiration for firms to attract more high-quality returnees and optimize their labor resource allocation.

Abstract Background Colorectal cancer (CRC) is a disease with high morbidity and mortality rates globally. Long noncoding RNAs (lncRNAs) play a fundamental role in tumor progression, and increasing attention has been paid to their role in CRC. This study aimed to determine the function of lncRNA DICER1 antisense RNA 1 (DICER1‐AS1) in CRC and confirm its potential regulatory mechanisms in CRC. Methods The publicly available dataset was used to assess DICER1‐AS1 function and expression in CRC. RT–qPCR or western blot assays were performed to verify DICER1‐AS1, miR‐650, and mitogen‐activated protein kinase 1 (MAPK1) expression in CRC cells or tissues. To determine the function of DICER1‐AS1, we performed CCK‐8, colony formation, transwell, cell cycle, and in vivo animal assays. Using RNA sequence analysis, luciferase reporter assays, and bioinformatics analysis, the connection between DICER1‐AS1, MAPK1, and miR‐650 was investigated. Results DICER1‐AS1 was significantly upregulated in CRC tissue compared to normal colon tissue. High DICER1‐AS1 expression suggested a poor prognosis in CRC patients. Functionally, upregulation of DICER1‐AS1 effectively promoted CRC proliferation, migration, and invasion ex vivo and tumor progression in vivo. Mechanistically, DICER1‐AS1 functions as a competitive endogenous RNA (ceRNA) that sponges miR‐650 to upregulate MAPK1, promotes ERK1/2 phosphorylation, and sequentially activates the MAPK/ERK signaling pathway. Conclusion Our investigations found that upregulation of DICER1‐AS1 activates the MAPK/ERK signaling pathway by sponging miR‐650 to promote CRC progression, revealing a possible clinically significant biomarker and therapeutic target.

Nonvolatile compact on-chip optical filters with a tunable spectral response are required in low-power optical communication systems and applications. By capping phase change materials (PCMs) films on a phase-shifted Bragg grating (PSBG), the key parameters of a filter such as center wavelength and extinction ratio can be tuned simultaneously for filtering or processing purposes. A 9 nm wavelength shift, and amplitude modulations of 16.1 dB in the transmission channel and 42.5 dB in the reflection channel while keeping the center wavelength unchanged are achieved in this filter at 1550 nm. Moreover, the device has a compact size of 500 nm × 31.9 $\mu$m and an insertion loss as low as -0.76 dB, making it ideal for large-scale integration. The advent of such compact, reconfigurable, nonvolatile optical filters opens up new avenues for next-generation low-power general-purpose photonic integrated circuits (PICs) and has potential applications in wavelength division multiplexing (WDM) systems, spectral shaping, and on-chip signal processors.

Fluoride is an essential micronutrient for humans. Nonetheless, when the amount of fluoride ion is greater than required, it will cause skeletal fluorosis and dental fluorosis to threaten human health. In this paper, a series of sodium alginate (SA)-based foam materials are prepared by freeze-drying technique and anchored with the nano-activated alumina (nAl2O3) in the SA to obtain a novel adsorbent of SA-nAl2O3 foam used for fluoride ions removal. The SA-nAl2O3 foam morphology was further explored and confirmed that nAl2O3 existed stably in the SA. The adsorption results showed that the maximal fluoride ion adsorption capacity was 5.09 mg/g with 20 mg/L fluorine solutions at a pH of 3. The adsorption isotherm fitted adequately to the Langmuir isotherm model, which demonstrated that the adsorption process is closer to monolayer adsorption. The adsorption kinetics behavior of SA-nAl2O3 foam was described by a pseudo-second-order model, and the adsorption process occurred by chemisorption. Adsorption thermodynamics analysis emphasized that the adsorption process was spontaneous and endothermic. The main mechanism of the foam is ion exchange. The SA-nAl2O3 foam exhibited excellent regeneration performance and stability after three cycles. HIGHLIGHTS A novel adsorption material of SA-nAl2O3 foam was obtained for fluoride ion removal.; SA-nAl2O3 foam exhibited steady fluoride ion adsorption capacity.; SA-nAl2O3 foam has excellent regenerability after three cycles;

Abstract Background We aimed to investigate response and prognostic factors in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic colorectal cancer (mCRC) and compare the curative effect on patients who received different therapy regimens (including chemotherapy and chemotherapy combined with targeted drugs). Methods We retrospectively analyzed all HER2 positive mCRC patients treated at Peking University Cancer Hospital between September 2011 and February 2021. We divided 63 HER2 positive mCRC into group A and group B according to the use of trastuzumab or not. Besides, we assigned four subgroups according to the first-line therapies of KRAS/NRAS/BRAF WT patients. The Kaplan–Meier estimator was used to calculate PFS and OS. Univariable analysis and Cox proportional hazards models were used to analyze the association between clinicopathological features and survival outcomes. Results Among 63 patients, 54 (85.7%) were KRAS/NRAS/BRAF wild-type (WT). Univariate analysis showed that the male sex, primary lesions in the right colon, simultaneous metastasis, and unresectable primary lesions were significant risk factors for poor survival of HER2 positive mCRC (P

Cell microenvironments in human body are always complex, dynamic, and asymmetric. Light-controlled materials can mimic different physical and chemical environments non-invasively, in site, and dynamically, as a result, is attracting increasing attention in tissue engineering, cancer biology, and regenerating medicine. In this review, we discuss different light-controlled materials regulating cell behaviors. By controlling mechanical or cell adhesion properties, these materials synthesized by functional proteins or light-sensitive chemical groups can mimic microenvironments and regulate cell behaviors like migration and differentiation.

In order to study the effect of soil salt content on the corrosion of buried metal by the stray current in urban rail transit, a small experimental platform for the buried metal corrosion is built. The corrosion rate and mass loss of buried carbon steel specimens in soil samples with or without DC stray current are measured and calculated when different content of NaCl is added into the soil samples, respectively. The experimental results show that the corrosion rate and mass loss of the buried metal increase with the increase of soil salt content. DC stray current will aggravate the corrosion of the buried metal. The corrosion degree of buried metal will be seriously aggravated under the coupling action of DC stray current and salt. When there is no DC stray curren, the corrosion degree of buried metal is relatively small, and the influence of soil salt content on the buried metal corrosion is also relatively small. Finally, a multiphysics simulation model corresponding to the experiment is established to verify the experimental results. The simulation results are basically consistent with the experimental results, which proves the accuracy of the experimental results. The research results can provide a theoretical basis for the corrosion protection design of subway stray current.

Plant phospholipase D (PLD) exerts important roles in various biological processes, such as intracellular signaling and morphological development. Our knowledge about early land plant PLDs is still underdeveloped. In this study, we identified 84 PLD genes in six mosses, i.e., Physcomitrella patens, Ceratodon purpureus, Fontinalis antipyretica, Pleurozium schreberi, Sphagnum magellanicum, and Sphagnum fallax. These PLDs were classified into four clades (I–IV). We showed that PLD underwent rapid expansion in mosses. A total of six conserved domains and two core HKD motifs were detected. Structure analysis uncovered that the moss PLDs from within a clade generally exhibited similar exon-intron organization. Cis-elements prediction and expression analyses indicated that P. patens PLDs had key roles in stress responsiveness and plant development. Particularly, about half of the P. patens PLDs (e.g., PpPLD1, PpPLD2, and PpPLD5) were differentially expressed under biotic and abiotic stresses. We also determined the expression pattern of P. patens PLD genes in various tissues and at different stages of development. Although the moss, clubmoss, liverwort, and fern PLDs evolved largely under functional constraints, we found episodic positive selection in the moss PLDs, e.g., C. purpureus PLD2 and P. patens PLD11. We infer that the evolutionary force acting on the PLDs may have facilitated moss colonization of land. Our work provides valuable insights into the diversification of moss PLD genes, and can be used for future studies of their functions.

Bacterial surface adhesion proteins are characterized by unusual mechanical properties. Here, the authors use atomic force microscopy-based technique to study a surface-anchoring protein Cpe0147 from Clostridium perfringens and show that an ester bond can withstand considerable mechanical forces and prevent complete protein unfolding.

Nanopores have been used for direct observation of RNA structure in native environments but have limited RNA differentiation capabilities. Here, the authors report on the use of Mycobacterium smegmatis porin A nanopores for the trapping and translocation identification of microRNA, siRNA, tRNA and ribosomal RNA.

Allosteric communication between distant parts of proteins controls many cellular functions, in which metal ions are widely utilized as effectors to trigger the allosteric cascade. Due to the involvement of strong coordination interactions, the energy landscape dictating the metal ion binding is intrinsically rugged. How metal ions achieve fast binding by overcoming the landscape ruggedness and thereby efficiently mediate protein allostery is elusive. By performing molecular dynamics simulations for the Ca2+ binding mediated allostery of the calmodulin (CaM) domains, each containing two Ca2+ binding helix-loop-helix motifs (EF-hands), we revealed the key role of water-bridged interactions in Ca2+ binding and protein allostery. The bridging water molecules between Ca2+ and binding residue reduces the ruggedness of ligand exchange landscape by acting as a lubricant, facilitating the Ca2+ coupled protein allostery. Calcium-induced rotation of the helices in the EF-hands, with the hydrophobic core serving as the pivot, leads to exposure of hydrophobic sites for target binding. Intriguingly, despite being structurally similar, the response of the two symmetrically arranged EF-hands upon Ca2+ binding is asymmetric. Breakage of symmetry is needed for efficient allosteric communication between the EF-hands. The key roles that water molecules play in driving allosteric transitions are likely to be general in other metal ion mediated protein allostery.

Abstract Background Predicting the possibility of ipsilateral lateral cervical lymph node metastasis (ipsi-LLNM) was crucial to the operation plan for patients with papillary thyroid carcinoma (PTC). This study aimed to investigate the independent risk factors for ipsi-LLNM in PTC patients by combining dual-energy computed tomography (DECT) with thyroid function indicators. Methods We retrospectively enrolled 406 patients with a pathological diagnosis of PTC from Jan 2016 to Dec 2019. Ensure the DECT images were clear and the thyroid function indicators were complete. Univariate and multivariate logistic analyses explored the independent risk factors for ipsi-LLNM. To evaluate the cutoff value of each risk factor by using receiver operating characteristic (ROC) curves. Results A total of 406 patients with PTC were analyzed, including 128 with ipsi-LLNM and 278 without ipsi-LLNM. There were statistical differences of parameters between the two groups (P 100.01 ng/mL, Anti-Tg > 89.43 IU/mL, IC in arterial phase > 3.4 mg/mL and IC in venous phase > 3.1 mg/mL. Conclusions The combined application of DECT quantitative parameters and thyroid function indicators can help clinicians accurately predict ipsi-LLNM before surgery, thereby assisting the individualized formulation of surgical procedures.

Abstract Background Erysipelas is a common skin infection that is prone to recur. Recurrent erysipelas has a severe effect on the quality of life of patients. The present study aimed to investigate the risk factors of recurrent erysipelas in adult Chinese patients. Methods A total of 428 Chinese patients with erysipelas who met the inclusion criteria were studied. The patients were divided into the nonrecurrent erysipelas group and the recurrent erysipelas group. Clinical data were collected on the first episode and relapse of erysipelas. The patients were followed up every 3 months. Statistical analysis was performed to analyze and determine the risk factors of erysipelas relapse. Results Univariate analysis was performed to analyze the data, including surgery, types of antibiotics administered in the first episode, obesity, diabetes mellitus, venous insufficiency, lymphedema, and malignancy. The differences between the groups were statistically significant (p

Background Disturbances are crucial in determining forest biodiversity, dynamics, and ecosystem functions. Surface fire is a significant disturbance in tropical forests, but research on the effect of surface fire on structuring species and functional composition in a community through time remains scarce. Using a 20-year dataset of tree demography in a seasonal evergreen tropical forest in Thailand, we specifically addressed two essential questions: (1) What is the pattern of temporal turnover in species and functional composition in a community with frequent fire disturbance? (2) How did the temporal turnover vary with tree size? Methods We analyzed species compositional and functional temporal turnovers in four different tree size classes among five tree censuses. We quantified species turnover by calculating Bray-Curtis dissimilarity, and investigated its underlying mechanisms by comparing pairwise dissimilarity of functional traits with simulations from null models. If fire disturbances contribute more to a stochastic process, the functional composition would display a random pattern. However, if they contribute more towards a deterministic process, the functional composition should reveal a non-random pattern. Results Over 20 years (1994–2014), we observed changes in species composition, whereas functional composition remained relatively stable. The temporal turnover patterns of species and functional compositions varied with tree sizes. In particular, temporal functional turnover shifted very little for large trees, suggesting that changes in species composition of larger trees are contributed by species with similar functional traits through time. The temporal functional composition turnovers of smaller trees (DBH ≤ 5 cm) were mostly at random. We detected a higher functional turnover than expected by null models in some quadrats throughout the 50-ha study plot, and their observed turnover varied with diameter classes. Conclusions Species compositional changes were caused by changes in the abundance of species with similar functional traits through time. Temporal functional turnover in small trees was random in most quadrats, suggesting that the recruits came from the equal proportions of surviving trees and new individuals of fast-growing species, which increased rapidly after fires. On the other hand, functional composition in big trees was more likely determined by surviving trees which maintained higher functional similarities than small trees through time. Fire disturbance is important for ecosystem functions, as changing forest fire frequency may alter forest turnover, particularly in functional composition in the new recruits of this forest.

BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. There are many uncommon and rare mutations in the EGFR gene. The efficacy of the EGFR-TKIs is largely unknown for cancers harboring uncommon or rare EGFR mutations.Case PresentationA 69-year-old woman was diagnosed with adenocarcinoma cT4N2M1c, stage IVB. Next-generation sequencing (NGS) confirmed a rare EGFR V786M mutation. During chemotherapy, immune checkpoint inhibitor (ICI), and anti-angiogenic treatment, no radiological response was observed. Subsequent third-generation EGFR TKI showed a remarkable therapeutic effect. Structural prediction revealed that the V786M mutation induces conformational change at the dimer interface, without altering the ATP binding to the EGFR tyrosine kinase domain (TKD). Consistently, docking simulations indicated that the affinity of ATP to the V786M mutant was not disturbed, which explained the TKI sensitivity.ConclusionsOur data confirmed the activating role on EGFR V786M mutation. Together with structural predictions and clinical evidence for activity of TKIs against EGFR V786M mutations, these findings warrant further investigation.

The rhizome is an important organ through which many perennial plants are able to propagate vegetatively. Its ecological role has been thoroughly studied on many grass species while the underlying genetic basis is mainly investigated using a rhizomatous wild rice species—Oryza longistaminata. Previous studies have revealed that the rhizome trait in O. longistaminata is jointly controlled by multiple loci, yet how these loci interact with each other remains elusive. Here, an F2 population derived from Oryza sativa (RD23) and O. longistaminata was used to map loci that affect rhizome-related traits. We identified 13 major-effect loci that may jointly control rhizomatousness in O. longistaminata and a total of 51 quantitative trait loci (QTLs) were identified to affect rhizome abundance. Notably, some of these loci were found to have effects on more than one rhizome-related trait. For each trait, a genetic network was constructed according to the genetic expectations of the identified loci. Furthermore, to gain an overview of the genetic regulation on rhizome development, a comprehensive network integrating all these individual networks was assembled. This network consists of three subnetworks that control different aspects of rhizome expression. Judging from the nodes’ role in the network and their corresponding traits, we speculated that qRHZ-3-1, qRHZ-4, qRHI-2, and qRHI-5 are the key loci for rhizome development. Functional verification using rhizome-free recombinant inbred lines (RILs) suggested that qRHI-2 and qRHI-5, two multi-trait controlling loci that appeared to be critical in our network analyses, are likely both needed for rhizome formation. Our results provide more insights into the genetic basis of rhizome development and may facilitate identification of key rhizome-related genes.

The drug-like compound PF846 and its derivatives inhibit the translation of specific mRNAs by the human ribosome. Here the authors show how PF846 arrests translation at the stop codon by slowing hydrolysis of the protein nascent chain at the ribosome P-site tRNA by eukaryotic release factor 1 (eRF1).

Tartary buckwheat microgreens (TBM) are popular worldwide products but display an extremely short shelf life. Thus, the effects of storage temperature, packaging material, and wash treatment on the quality and shelf life were analyzed. Headspace composition, weight loss, electrolyte leakage, microbial population and sensory quality were investigated during storage. Results showed that shelf life and quality of TBM decreased with the increment of storage temperature when stored at 5–25 °C. During 5 °C storage, LDPE bags were the best packaging materials for preserving the quality of LDPE, PE and HDPE bags. On the basis of 5 °C and LDPE packages, ClO2 + citric acid wash treatment could further inhibit quality deterioration and extend the shelf life. The results demonstrated bioactive constituents and antioxidant capacity were significantly affected by storage time. The study provides insights into developing optimal packaging and storage conditions for TBM.

Abstract Objectives This study aims to explore the reliability, validity, and feasibility of Clinically Useful Depression Outcome Scale (CUDOS) in screening mixed features in patients diagnosed with mania. Methods A total of 109 patients with (hypo‐) manic episode were recruited. The reliability of Chinese version of CUDOS (CUDOS‐C) were analyzed with Cronbach's alpha and intraclass correlation coefficient (ICC). Spearman correlation coefficient was used to analyze the validity by comparing the correlation between CUDOS‐C and Patient Health Questionnaire‐9 (PHQ‐9), 32‐item Hypomania Checklist (HCL‐32). The score of MINI (hypo‐) manic episode with mixed features—DSM‐5 Module—Chinese version(MINI‐M‐C) ≥ 2 was considered as the gold standard of mixed features, and the receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cut‐off values of CUDOS‐C score. Results The Cronbach's alpha value of CUDOS‐C was 0.898, and the ICC of CUDOS‐C test‐retest was 0.880 (95% CI: 0.812‐0.923, p

Abstract Background Fructus Psoraleae is the seed of Psoralea corylifolia Linn. Fructus Psoraleae has been shown to be effective in treating some skin diseases, such as vitiligo. As a main ingredient in five types of herbs in the Qubaibabuqi tablet formula, Fructus Psoraleae plays an important role in the treatment of vitiligo. Fructus Psoraleae has potential hepatotoxicity, thus Qubaibabuqi tablets also have potential liver toxicity. Case presentation A 53-year-old woman who was diagnosed with vitiligo in September 2017 was treated with Qubaibabuqi tablets. After approximately 7 months of treatment, the patient developed a severe, diffuse yellow staining of the skin and sclera in March 2018. On admission, she was diagnosed with acute cholestatic hepatitis associated with Fructus Psoraleae. Despite receiving active treatment, her condition rapidly deteriorated and she died 5 days later due to acute liver failure and multiple organ dysfunction. To the best of our knowledge, there are only six reported cases of liver injury associated with Fructus Psoraleae described in the English language literature; however, cases of acute liver failure associated with the use of Fructus Psoraleae have not been described. Conclusion As a main ingredient in the Qubaibabuqi tablet formula, Fructus Psoraleae has potential hepatotoxicity. This potentially fatal adverse effect should be considered when physicians prescribe Qubaibabuqi tablets.

Milk casein and triglyceride content are important production traits in goats. Studies on mechanisms in milk casein secretion and mammary gland development is essential for milk goat breeding. miRNAs play an important role in goat lactation. While novel-miR-3880 is highly expressed at goat peak lactation stage, its molecular mechanism has not been studied. The purpose of the present study was to explore the relationship between novel-miR-3880 and lactation, as well as to construct a network among novel-miR-3880, ciRNA13761, and E74 like ETS transcription factor 2 (ELF2), thus further exploring their potential roles in milk components and mammary gland development. ELF2 was previously proven to be important in cell survival and proliferation, and 3′-UTR of ELF2 was predicted to have binding sites of novel-miR-3880. Our study found that the overexpression of novel-miR-3880 exerted anti-apoptotic and proliferative roles in GMEC, induced a boost in triglyceride synthesis, and caused a decrease in α s1-, α s2-, and β-casein, but an increase in κ-casein secretion. Furthermore, treatment in mice indicated that novel-miR-3880 could promote mammary gland development and extend the lactation period, while novel-miR-3880 expression was found to be suppressed by ciRNA13761 as a miRNA sponge. The present study explores a mechanism of triglyceride synthesis and casein secretion, and reveals a crosstalk between ciRNA13761/novel-miR-3880/ELF2 axis and PI3K/AKT/mTOR/S6K1 pathway, to gain a better understanding of lactation traits in dairy goats.

Objective Versican (VCAN) has been reported as a potential biomarker in some cancers. However, its role in gastric cancer (GC) is poorly understood. Methods Associations between clinical variables and VCAN were assessed. The diagnostic value of VCAN expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. Cox regression and the Kaplan–Meier method were used to explore clinicopathologic factors related to overall survival in GC patients. The Gene Expression Omnibus and the Human Protein Atlas were used for further validation. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset. Results High expression of VCAN was associated with high stage and T classification in GC. The area under the ROC curve was 0.853. Patients with high VCAN expression had worse prognoses than those with low VCAN expression. Multivariate analysis showed that VCAN was an independent risk factor for overall survival in both cohorts. GSEA identified pathways involved in cancer, ECM-receptor interaction, Wnt signaling, T cell receptor signaling, and chemokine signaling as differentially enriched in GCs with high VCAN expression. Conclusion We demonstrated that VCAN is expressed at high levels in GC, and represents a potential independent molecular marker for diagnosis and prognosis of GC.

Autonomous driving is a popular and promising field in artificial intelligence. Rapid decision of the next action according to the latest few actions and status, such as acceleration, brake, and steering angle, is a major concern for autonomous driving. There are some learning methods, such as reinforcement learning which automatically learns the decision. However, it usually requires large volume of samples. In this paper, to reduce the sample size, we exploit the deep Gaussian process, where a regression model is trained on small sample datasets and captures the most significant features correctly. Besides, to realize the real-time and close-loop control, we combine the feedback control into the process. Experimental results on the Torcs simulation engine illustrate smooth driving on virtual road which can be achieved. Compared with the amount of training data in deep reinforcement learning, our method uses only 0.34% of its size and obtains similar simulation results. It may be useful for real road tests in the future.

Recent advances in DNA sequencing methods revolutionized biology by providing highly accurate reads, with high throughput or high read length. These read data are being used in many biological and medical applications. Modern DNA sequencing methods have no equivalent in protein sequencing, severely limiting the widespread application of protein data. Recently, several optical protein sequencing methods have been proposed that rely on the fluorescent labeling of amino acids. Here, we introduce the reprotonation-deprotonation protein sequencing method. Unlike other methods, this proposed technique relies on the measurement of an electrical signal and requires no fluorescent labeling. In reprotonation-deprotonation protein sequencing, the terminal amino acid is identified through its unique protonation signal, and by repeatedly cleaving the terminal amino acids one-by-one, each amino acid in the peptide is measured. By means of simulations, we show that, given a reference database of known proteins, reprotonation-deprotonation sequencing has the potential to correctly identify proteins in a sample. Our simulations provide target values for the signal-to-noise ratios that sensor devices need to attain in order to detect reprotonation-deprotonation events, as well as suitable pH values and required measurement times per amino acid. For instance, an SNR of 10 is required for a 61.71% proteome recovery rate with 100 ms measurement time per amino acid.

Abstract Background Pyogenic liver abscess(PLA) has become common in patients with diabetes mellitus (DM), but it is unclear whether differences exist between patients with and without DM. A retrospective study was performed to identify these differences, summarize the clinical experience, and improve the diagnosis and treatment of PLA. Methods The patients were enrolled in a teaching hospital from January 2012 to December 2016. The patients were separated into two groups based on comorbidity with diabetes mellitus (DM). The DM group was further separated into two subgroups according to the HbA1C concentration to investigate whether glycaemic control affected the clinical characteristics of PLA patients with DM. Chi-square, Fisher’s exact test, and t-tests were used to analyse and evaluate differences between the two groups. Results Two hundred and forty-six PLA patients were identified and 90 (36.6%) had comorbid DM. Patients with DM were older, had higher levels of alkaline phosphatase and γ-glutamyl transferase, hypertension, a loss of body weight, a single abscess, and combined antibiotic therapy with the use of carbapenems and Klebsiella pneumoniae in their blood cultures but a less frequent history of abdominal surgery and Escherichia coli in their pus cultures. When DM patients were compared to non-DM patients, each of these differences was significant (P

The information gap in the M&A market hinders acquirers from effectively identifying high-quality targets. We examine whether VC/PEs convey information content in the M&A market and whether acquirers can use such information to identify high-quality targets. We show that VC/PEs have significant information content and can signal high-quality target companies via “certification”. When acquirers lack acquisition experience and targets are located in inferior information environments, VC/PE “certification” is more significant. The better reputation a VC/PE has, the more information it conveys. Syndicate VC/PEs convey stronger information than independent VC/PEs. We also find that acquirers do not pay higher premiums for high-quality targets. Overall, our results suggest that VC/PEs have value relevance in the M&A market, confirming their “certification” role. We present means for acquirers to select high-quality targets and investors to build efficient portfolios. Keywords: M&A, Certification, VC/PEs, Information content

Trajectory tracking is a key technology for precisely controlling autonomous vehicles. In this paper, we propose a trajectory-tracking method based on model predictive control. Instead of using the forward Euler integration method, the backward Euler integration method is used to establish the predictive model. To meet the real-time requirement, a constraint is imposed on the control law and the warm-start technique is employed. The MPC-based controller is proved to be stable. The simulation results demonstrate that, at the cost of no or a little increase in computational time, the tracking performance of the controller is much better than that of controllers using the forward Euler method. The maximum lateral errors are reduced by 69.09%, 47.89% and 78.66%. The real-time performance of the MPC controller is good. The calculation time is below 0.0203 s, which is shorter than the control period.

The coordinated control of a blended braking system is always a difficult task. In particular, blended braking control becomes more challenging when the braking actuator has an input time-delay and some states of the braking system cannot be measured. In order to improve the tracking performance, a coordinated control system was designed based on the input time-delay and state observation for a blended braking system comprising a motor braking system and friction braking system. The coordinated control consists of three parts: Sliding mode control, a multi-input single-output observer, and time-delay estimation-based Smith Predictor control. The sliding mode control is used to calculate the total command braking torque according to the desired braking performance and vehicle states. The multi-input single-output observer is used to simultaneously estimate the input time-delay and output braking torque of the friction braking system. With time-delay estimation-based Smith Predictor control, the friction braking system is able to effectively track the command braking torque of the friction braking system. The tracking of command braking torque is realized through the coordinated control of the motor braking system and friction braking system. In order to validate the effectiveness of the proposed approach, numerical simulations on a quarter-vehicle braking model were performed.

Pityriasis rosea is a papulosquamous skin disorder that occurs most commonly between the ages of 10 and 35 years. Recurrent pityriasis rosea is rare. We report a patient suffering from recurrent pityriasis rosea, whose etiology may be related to either vaccine-induced stimulation of the immune system, or some rare vaccine component(influenza A [H1N1] vaccine, hepatitis B vaccine). We believe that such a case is unique and it has not been reported previously. The patient was successfully treated with a combination of oral cetirizine, a topical steroid cream, and narrowband-ultraviolet B phototherapy. The symptoms of this disorder should be recognized by dermatologists.

Vehicle dynamic parameters are of vital importance to establish feasible vehicle models which are used to provide active controls and automated driving control. However, most vehicle dynamics parameters are difficult to obtain directly. In this paper, a new method, which requires only conventional sensors, is proposed to estimate vehicle dynamic parameters. The influence of vehicle dynamic parameters on vehicle dynamics often involves coupling. To solve the problem of coupling, a two-stage estimation method, consisting of multiple-models and the Unscented Kalman Filter, is proposed in this paper. During the first stage, the longitudinal vehicle dynamics model is used. Through vehicle acceleration/deceleration, this model can be used to estimate the distance between the vehicle centroid and vehicle front, the height of vehicle centroid and tire longitudinal stiffness. The estimated parameter can be used in the second stage. During the second stage, a single-track with roll dynamics vehicle model is adopted. By making vehicle continuous steering, this vehicle model can be used to estimate tire cornering stiffness, the vehicle moment of inertia around the yaw axis and the moment of inertia around the longitudinal axis. The simulation results show that the proposed method is effective and vehicle dynamic parameters can be well estimated.

Profilin is an actin-sequestering protein and plays key role in regulating the polarized growth of actin filament. Binding of profilin to monomeric actin (G-actin) allows continuous elongation at the barbed end (BE), but not the pointed end, of filament. How G-actin exchanges between the profilin-sequestered state and the filament state (F-actin) to support the BE elongation is not well understood. Here, we investigate the involved molecular mechanism by constructing a multi-basin energy landscape model and performing molecular simulations. We showed that the actin exchanging occurs by forming a ternary complex. The interactions arising from the BE binding drive the conformational change of the attached G-actin in the ternary complex from twist conformation to more flatten conformation without involving the change of nucleotide state, which in turn destabilizes the actin–profilin interface and promotes the profilin stripping event through allosteric coupling. We also showed that attachment of free profilin to the BE induces conformational change of the BE actin and facilitates its stripping from the filament. These results suggest a molecular stripping mechanism of the polarized actin filament growth dynamics controlled by the concentrations of the actin–profilin dimer and the free profilin, in which the allosteric feature of the monomeric actin plays crucial role.

This paper investigates whether religious traditions influence firm-specific crash risk in China. Using a sample of A-share listed firms from 2003 to 2013, we provide evidence that the more intense the religious environment, the lower the stock price crash risk, implying that religion plays an important role in Chinese corporate governance. Further, we find that (1) religion affects stock price crash risk by reducing earnings management and the management perk problem; (2) different religions have different effects, and Taoism, in particular, is unrelated to crash risk; and (3) the effects of religion are more pronounced with higher quality corporate governance and a stronger legal environment. Religion constrains the management agency problem, thus reducing stock price crash risk in China. Our paper enriches the literature on stock price crash risk and religion, and on new economic geography.

Quality assessment is essential for the computational prediction and design of RNA tertiary structures. To date, several knowledge-based statistical potentials have been proposed and proved to be effective in identifying native and near-native RNA structures. All these potentials are based on the inverse Boltzmann formula, while differing in the choice of the geometrical descriptor, reference state, and training dataset. Via an approach that diverges completely from the conventional statistical potentials, our work explored the power of a 3D convolutional neural network (CNN)-based approach as a quality evaluator for RNA 3D structures, which used a 3D grid representation of the structure as input without extracting features manually. The RNA structures were evaluated by examining each nucleotide, so our method can also provide local quality assessment. Two sets of training samples were built. The first one included 1 million samples generated by high-temperature molecular dynamics (MD) simulations and the second one included 1 million samples generated by Monte Carlo (MC) structure prediction. Both MD and MC procedures were performed for a non-redundant set of 414 RNAs. For two training datasets (one including only MD training samples and the other including both MD and MC training samples), we trained two neural networks, named RNA3DCNN_MD and RNA3DCNN_MDMC, respectively. The former is suitable for assessing near-native structures, while the latter is suitable for assessing structures covering large structural space. We tested the performance of our method and made comparisons with four other traditional scoring functions. On two of three test datasets, our method performed similarly to the state-of-the-art traditional scoring function, and on the third test dataset, our method was far superior to other scoring functions. Our method can be downloaded from https://github.com/lijunRNA/RNA3DCNN.

Cytoplasmic dynein is a giant ATP-driven molecular motor that proceeds to the minus end of the microtubule (MT). Dynein hydrolyzes ATP in a ring-like structure, containing 6 AAA+ (ATPases associated with diverse cellular activities) modules, which is ~15 nm away from the MT binding domain (MTBD). This architecture implies that long-distance allosteric couplings exist between the AAA+ ring and the MTBD in order for dynein to move on the MT, although little is known about the mechanisms involved. Here, we have performed comprehensive molecular simulations of the dynein motor domain based on pre- and post- power-stroke structural information and in doing so we address the allosteric conformational changes that occur during the power-stroke and recovery-stroke processes. In the power-stroke process, the N-terminal linker movement was the prerequisite to the nucleotide-dependent AAA1 transition, from which a transition cascade propagated, on average, in a circular manner on the AAA+ ring until it reached the AAA6/C-terminal module. The recovery-stroke process was initiated by the transition of the AAA6/C-terminal, from which the transition cascade split into the two directions of the AAA+ ring, occurring both clockwise and anti-clockwise. In both processes, the MTBD conformational change was regulated by the AAA4 module and the AAA5/Strut module.

The knowledge of the tertiary structure of RNA loops is important for understanding their functions. In this work we develop an efficient approach named RNApps, specifically designed for predicting the tertiary structure of RNA loops, including hairpin loops, internal loops, and multi-way junction loops. It includes a probabilistic coarse-grained RNA model, an all-atom statistical energy function, a sequential Monte Carlo growth algorithm, and a simulated annealing procedure. The approach is tested with a dataset including nine RNA loops, a 23S ribosomal RNA, and a large dataset containing 876 RNAs. The performance is evaluated and compared with a homology modeling based predictor and an ab initio predictor. It is found that RNApps has comparable performance with the former one and outdoes the latter in terms of structure predictions. The approach holds great promise for accurate and efficient RNA tertiary structure prediction.

Proteins perform their biological functions through motion. Although high throughput prediction of the three-dimensional static structures of proteins has proved feasible using deep-learning-based methods, predicting the conformational motions remains a challenge. Purely data-driven machine learning methods encounter difficulty for addressing such motions because available laboratory data on conformational motions are still limited. In this work, we develop a method for generating protein allosteric motions by integrating physical energy landscape information into deep-learning-based methods. We show that local energetic frustration, which represents a quantification of the local features of the energy landscape governing protein allosteric dynamics, can be utilized to empower AlphaFold2 (AF2) to predict protein conformational motions. Starting from ground state static structures, this integrative method generates alternative structures as well as pathways of protein conformational motions, using a progressive enhancement of the energetic frustration features in the input multiple sequence alignment sequences. For a model protein adenylate kinase, we show that the generated conformational motions are consistent with available experimental and molecular dynamics simulation data. Applying the method to another two proteins KaiB and ribose-binding protein, which involve large-amplitude conformational changes, can also successfully generate the alternative conformations. We also show how to extract overall features of the AF2 energy landscape topography, which has been considered by many to be black box. Incorporating physical knowledge into deeplearning-based structure prediction algorithms provides a useful strategy to address the challenges of dynamic structure prediction of allosteric proteins. [ABSTRACT FROM AUTHOR]