TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis

The matrix-specific protein periostin (POSTN) is up-regulated in human cancers and associated with cancer growth, metastasis and angiogenesis. Although the stroma of cancer tissues is the main source of POSTN, it is still unclear how POSTN plays a role to facilitate the interplay between cancer cells and cancer-associated fibroblasts (CAFs) in head and neck cancer (HNC), thereby promoting tumorigenesis via modifying the tumor microenvironment. Herein, we have performed studies to investigate POSTN and its role in HNC microenvironment. Our results indicated that POSTN was significantly up-regulated in HNCs, especially in the tissues with lymph node metastasis. Moreover, POSTN was highly enriched in the stroma of cancer tissues and produced mainly by CAFs. More importantly, we have pinpointed TGF-β3 as the major upstream molecular that triggers the induction of POSTN in CAFs. As such, during the interaction between fibroblasts and cancer cells, the increased stromal POSTN induced by TGF-β3 directly accelerated the growth, migration and invasion of cancer cells. Hence, our study has provided a novel modulative role for POSTN on HNC progression and further reveals POSTN as an effective biomarker to predict metastasis as well as a potential cancer therapeutic target

CogVLM: Visual Expert for Pretrained Language Models

We introduce CogVLM, a powerful open-source visual language foundation model. Different from the popular shallow alignment method which maps image features into the input space of language model, CogVLM bridges the gap between the frozen pretrained language model and image encoder by a trainable visual expert module in the attention and FFN layers. As a result, CogVLM enables deep fusion of vision language features without sacrificing any performance on NLP tasks. CogVLM-17B achieves state-of-the-art performance on 10 classic cross-modal benchmarks, including NoCaps, Flicker30k captioning, RefCOCO, RefCOCO+, RefCOCOg, Visual7W, GQA, ScienceQA, VizWiz VQA and TDIUC, and ranks the 2nd on VQAv2, OKVQA, TextVQA, COCO captioning, etc., surpassing or matching PaLI-X 55B. Codes and checkpoints are available at https://github.com/THUDM/CogVLM

Identification of immune-related genes and small-molecule drugs in hypertension-induced left ventricular hypertrophy based on machine learning algorithms and molecular docking

BackgroundLeft ventricular hypertrophy (LVH) is a common consequence of hypertension and can lead to heart failure. The immune response plays an important role in hypertensive LVH; however, there is no comprehensive method to investigate the mechanistic relationships between immune response and hypertensive LVH or to find novel therapeutic targets. This study aimed to screen hub immune-related genes involved in hypertensive LVH as well as to explore immune target-based therapeutic drugs.Materials and methodsRNA-sequencing data from a mouse model generated by angiotensin II infusion were subjected to weighted gene co-expression network analysis (WGCNA) to identify core expression modules. Machine learning algorithms were applied to screen immune-related LVH characteristic genes. Heart structures were evaluated by echocardiography and cardiac magnetic resonance imaging (CMRI). Validation of hub genes was conducted by RT-qPCR and western blot. Using the Connectivity Map database and molecular docking, potential small-molecule drugs were explored.ResultsA total of 1215 differentially expressed genes were obtained, most of which were significantly enriched in immunoregulation and collagen synthesis. WGCNA and multiple machine learning strategies uncovered six hub immune-related genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict hypertensive LVH diagnosis. Immune analysis revealed that fibroblasts and macrophages were closely correlated with hypertensive LVH, and hub gene expression was significantly associated with these immune cells. A regulatory network of transcription factor-mRNA and a ceRNA network of miRNA-lncRNA was established. Notably, six hub immune-related genes were significantly increased in the hypertensive LVH model, which were positively linked to left ventricle wall thickness. Finally, 12 small-molecule compounds with the potential to reverse the high expression of hub genes were ruled out as potential therapeutic agents for hypertensive LVH.ConclusionThis study identified and validated six hub immune-related genes that may play essential roles in hypertensive LVH, providing new insights into the potential pathogenesis of cardiac remodeling and novel targets for medical interventions

Multiomics Analyses Reveal DARS1-AS1/YBX1-Controlled Posttranscriptional Circuits Promoting Glioblastoma Tumorigenesis/Radioresistance

The glioblastoma (GBM) stem cell-like cells (GSCs) are critical for tumorigenesis/therapeutic resistance of GBM. Mounting evidence supports tumor-promoting function of long noncoding RNAs (lncRNAs), but their role in GSCs remains poorly understood. By combining CRISPRi screen with orthogonal multiomics approaches, we identified a lncRNA DARS1-AS1-controlled posttranscriptional circuitry that promoted the malignant properties of GBM cells/GSCs. Depleting DARS1-AS1 inhibited the proliferation of GBM cells/GSCs and self-renewal of GSCs, prolonging survival in orthotopic GBM models. DARS1-AS1 depletion also impaired the homologous recombination (HR)-mediated double-strand break (DSB) repair and enhanced the radiosensitivity of GBM cells/GSCs. Mechanistically, DARS1-AS1 interacted with YBX1 to promote target mRNA binding and stabilization, forming a mixed transcriptional/posttranscriptional feed-forward loop to up-regulate expression of the key regulators of G1-S transition, including E2F1 and CCND1. DARS1-AS1/YBX1 also stabilized the mRNA of FOXM1, a master transcription factor regulating GSC self-renewal and DSB repair. Our findings suggest DARS1-AS1/YBX1 axis as a potential therapeutic target for sensitizing GBM to radiation/HR deficiency-targeted therapy

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Role of Reactive Oxygen Species and Nitric Oxide in the Inhibition of Trichophyton rubrum Growth by HaCaT Cells

Trichophyton rubrum (T. rubrum) is one of the most important agents of dermatophyte infection in humans. The aim of this experiment was to evaluate the effect of HaCaT cells on T. rubrum, investigate the responsible mechanism of action, and explore the role of reactive oxygen species (ROS) and nitric oxide (NO) in the inhibition of T. rubrum growth by HaCaT cells. The viability of fungi treated with HaCaT cells alone and with HaCaT cells combined with pretreatment with the NADPH oxidase inhibitor (DPI) or the nitric oxide synthase (NOS) inhibitor L-NMMA was determined by enumerating the colony-forming units. NOS, ROS, and NO levels were quantified using fluorescent probes. The levels of the NOS inhibitor asymmetric dimethylarginine (ADMA) were determined by enzyme-linked immunosorbent assay (ELISA). Micromorphology was observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, fungal keratinase activity was assessed by measuring dye release from keratin azure. In vitro fungal viability, keratinase activity, and ADMA content decreased after HaCaT cell intervention, whereas the levels of ROS, NO, and NOS increased. The micromorphology was abnormal. Fungi pretreated with DPI and L-NMMA exhibited opposite effects. HaCaT cells inhibited the growth and pathogenicity of T. rubrum in vitro. A suggested mechanism is that ROS and NO play an important role in the inhibition of T. rubrum growth by HaCaT cells

Estimating the population of female sex workers in two Chinese cities on the basis of the HIV/AIDS behavioural surveillance approach combined with a multiplier method

The original publication may be found at www.bmj.comObjective: To estimate the size of the population of female sex workers (FSWs) on the basis of the HIV/AIDS behavioural surveillance approach in two Chinese cities, using a multiplier method. Method: Relevant questions were inserted into the questionnaires given to two behavioural surveillance groups—female attendees of sexually transmitted disease (STD) clinics and FSWs. The size of the FSW population was derived by multiplying the number of FSWs in selected STD clinics during the study period by the proportion of FSW population who reported having attended the selected STD clinics during the same period. Results: The size of the FSW population in the urban area of Xingyi, China, was estimated to be about 2500 (95% CI 2000 to 3400). This accounted for 3.6% of the total urban adult female population. There were an estimated 17 500 FSWs in the urban area of Guiyang, China (95% CI 10 300 to 31 900) or about 3.4% of its total urban adult female population (rounded to the nearest 100). Conclusions: The multiplier method could be a useful and cost-effective approach to estimate the FSW population, especially suitable in countries where HIV behavioural surveillance has been established in high-risk populations.Dapeng Zhang, Fan Lv, Liyan Wang, Liangxian Sun, Jian Zhou, Wenyi Su, and Peng B

Phenoloxidase, an effective bioactivity target for botanical insecticide screening from green walnut husks

<p>Phenoloxidase, a critical enzyme in insects, may serve as a promising target in botanical insecticide development. In an effort to identify active ingredients with insecticidal properties in green walnut husks, juglone and plumbagin were isolated from the chloroform extract using phenoloxidase as bioactive target with the IC₅₀ of 0.247 g/L and 0.256 g/L, respectively. After an artificial diet feeding of the juglone or plumbagin, more than 50% corrected mortality in stomach toxicity form was observed in <i>Pieris rapae</i> Linne larvae and <i>Helicoverpa armigera</i> Hübner larvae at the concentration ≥0.01 g/L, the LC₅₀ of juglone and plumbagin for two kinds of insects were determined as 0.012, 0.011 and 0.022, 0.030 g/L, respectively. This research indicated the significance of PO as bioactive target in pesticides identification and also shed light on the development of phenoloxidase inhibitor as promising botanical insecticides in the future.</p

Analysis of the Subdivision Errors of Photoelectric Angle Encoders and Improvement of the Tracking Precision of a Telescope Control System

Photoelectric angle encoders, working as position sensors, have a great influence on the accuracy and stability of telescope control systems (TCS). In order to improve the tracking precision of TCS, a method based on subdivision error compensation for photoelectric angle encoders is proposed. First, a mathematical analysis of six types of subdivision errors (DC error, phase error, amplitude error, harmonic error, noise error, and quantization error) is presented, which is different from the previously used analysis based on the Lissajous figure method. In fact, we believe that a mathematical method is more efficient than the figure method for the expression of subdivision errors. Then, the distribution law and period length of each subdivision error are analyzed. Finally, an error compensation algorithm is presented. In a real TCS, the elevation jittering phenomenon occurs, which indicates that compensating for the amplitude error is necessary. A feed-forward loop is then introduced into the TCS, which is position loop- and velocity loop-closed, leading to a decrease of the tracking error by nearly 54.6%, from 2.31&rdquo; to 1.05&rdquo;, with a leading speed of 0.25&deg;/s, and by 40.5%, from 3.01&rdquo; to 1.79&rdquo;, with a leading speed of 1&deg;/s. This method can realize real-time compensation and improve the ability of TCS without any change of the hardware. In addition, independently of the environment and the kind of control strategy used, this method can also improve the tracking precision presumably because it compensates the measuring error inside the photoelectric angle encoder

Recycling of spent lithium-ion batteries in view of green chemistry

Recycling of spent lithium-ion batteries (LIBs) is of great importance for both critical metal supply and environmental protection. Although the physical chemistry is still focused on pyrometallurgy, hydrometallurgy and electrometallurgy, state-of-the-art recycling technologies are a trend that is turning towards being more material/energy efficient in line with the principles of green chemistry. For instance, selective recycling of specified metals and direct regeneration of battery materials are being trialled to develop short-cut processes that prevent secondary pollution generation and improve the atomic economy during the whole recycling process. In this review, a number of technologies for recycling spent LIBs are overviewed, especially at different recycling stages to stepwise recover battery materials. It is clearly understood that extraction of critical metals and subsequent regeneration of materials are only part of the recycling process, while pretreatment to obtain black mass powder from battery cells and pollution control, in view of the recycling process to minimise environmental impact, are also extremely important. Furthermore, green design of batteries, as well as process design in view of the whole life cycle of LIBs, are topping the list of the research which requires profound and elaborate efforts. It is expected that this review could provide a guideline for implementing green chemistry principles into spent LIB recycling and stimulate further discussions on improving the green degree of the process