Effects of tumor metabolic microenvironment on regulatory T cells

Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body’s immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects the biological characteristics of the cells infiltrating them. Regulatory T cells (Tregs) are a subset of T cells that regulate immune responses in the body. They exist in large quantities in the tumor microenvironment and exert immunosuppressive effects. The main effect of tumor microenvironment on Tregs is to promote their differentiation, proliferation, secretion of immunosuppressive factors, and chemotactic recruitment to play a role in immunosuppression in tumor tissues. This review focuses on cell metabolism reprogramming and the most significant features of the tumor microenvironment relative to the functional effects on Tregs, highlighting our understanding of the mechanisms of tumor immune evasion and providing new directions for tumor immunotherapy

Establishment and characterization of immortalized human eutopic endometrial stromal cells.

PROBLEM(#br)The application of primary eutopic endometrial cells from endometriosis patients in research is restricted for short life span, dedifferentiation of hormone responsiveness.(#br)METHOD OF STUDY(#br)Human telomerase reverse transcriptase (hTERT)-induced immortalized cells (iheESCs) were infected by lentivirus. mRNA level was examined by qRT-PCR, and protein expression was quantified by Western blot. CCK-8 and EdU assay were assigned to assess the proliferation. The migration and invasion of cells were assessed by transwell assay. Clone formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities.(#br)RESULTS(#br)hTERT mRNA and protein were significantly expressed higher in iheESCs compared to primary cells. iheESCs grew without morphological change for 42 passages which is much longer than 18 passages of primary cells. There was no obvious difference between primary cells and iheESCs in growth, mobility, and chromosome karyotype. Furthermore, the expression of epithelial-mesenchymal transition (EMT) markers and estrogen/progesterone receptors remained unchanged. The decidualization of iheESCs could be induced by progesterone and cAMP. Estrogen increased the proliferation and mobility of iheESCs, and lipopolysaccharides (LPS) induced the IL-1β and IL-6 promoting inflammatory response. The colony-forming ability of iheESCs, like primary cells, was lower than Ishikawa cells. In addition, tumorigenicity assay indicated that iheESCs were unable to trigger tumor formation in BALB/c nude mouse.(#br)CONCLUSIONS(#br)This study established and characterized iheESCs that kept the cellular physiology of primary cells and were not available with tumorigenic ability. Thus, iheESCs would be useful as in vitro cell model to investigate pathogenesis of endometriosis

Anti-Inflammatory Effects of the Bioactive Compound Ferulic Acid Contained in Oldenlandia diffusa

Objectives. This study aimed to identify the active compounds in Oldenlandia diffusa (OD) decoction and the compounds absorbed into plasma, and to determine whether the absorbed compounds derived from OD exerted any anti-inflammatory effects in rats with collagen induced arthritis (CIA). Methods. The UPLC-PDA (Ultra Performance Liquid Chromatography Photo-Diode Array) method was applied to identify the active compounds both in the decoction and rat plasma. The absorbable compound was administered to the CIA rats, and the effects were dynamically observed. X-ray films of the joints and HE stain of synovial tissues were analyzed. The levels of IL-1β and TNF-α in the rats from each group were measured by means of ELISA. The absorbed compound in the plasma of CIA rats was identified as ferulic acid (FA), following OD decoction administration. Two weeks after the administration of FA solution or OD decoction, the general conditions improved compared to the model group. The anti-inflammatory effect of FA was inferior to that of the OD decoction (P<0.05), based on a comparison of IL-1β TNF-α levels. FA from the OD decoction was absorbed into the body of CIA rats, where it elicited anti-inflammatory responses in rats with CIA. Conclusions. These results suggest that FA is the bioactive compound in OD decoction, and FA exerts its effects through anti-inflammatory pathways

Multiple mobile excitons manifested as sidebands in metallic phase of TaSe₃

Excitons are bound states between electrons and holes, whose charge neutrality and a priori itinerant nature make them interesting as potential transmitters of information. However, the demonstration of the mobility of such composite excitations has remained inaccessible to traditional optical experiments which only create and detect excitons with negligible momentum or group velocity. Here, we use angle-resolved photoemission spectroscopy (ARPES) to detect dispersing excitons in the quasi-one-dimensional metallic trichalcogenide TaSe3. While screening usually suppresses exciton formation in metals, the low density of conduction electrons, the low dimensionality, and two many-body effects in TaSe3 favor them. First, the conduction band is renormalized close to the Fermi surface, forming a band of heavy polarons. Second, the poorly screened interaction between a photo-induced valence hole and these polarons leads to various distinct excitonic bound states, which we interpret as intrachain and interchain excitons, and possibly even trions. The thresholds for the formation of a photohole together with an exciton show up in the form of unusual side bands in the ARPES spectra. They are nearly parallel to the bare valence band, but lie at lower excitation energies. Furthermore, we find that the energy separation of the side bands can be tuned by surface doping

Secrets of RLHF in Large Language Models Part I: PPO

Large language models (LLMs) have formulated a blueprint for the advancement of artificial general intelligence. Its primary objective is to function as a human-centric (helpful, honest, and harmless) assistant. Alignment with humans assumes paramount significance, and reinforcement learning with human feedback (RLHF) emerges as the pivotal technological paradigm underpinning this pursuit. Current technical routes usually include \textbf{reward models} to measure human preferences, \textbf{Proximal Policy Optimization} (PPO) to optimize policy model outputs, and \textbf{process supervision} to improve step-by-step reasoning capabilities. However, due to the challenges of reward design, environment interaction, and agent training, coupled with huge trial and error cost of large language models, there is a significant barrier for AI researchers to motivate the development of technical alignment and safe landing of LLMs. The stable training of RLHF has still been a puzzle. In the first report, we dissect the framework of RLHF, re-evaluate the inner workings of PPO, and explore how the parts comprising PPO algorithms impact policy agent training. We identify policy constraints being the key factor for the effective implementation of the PPO algorithm. Therefore, we explore the PPO-max, an advanced version of PPO algorithm, to efficiently improve the training stability of the policy model. Based on our main results, we perform a comprehensive analysis of RLHF abilities compared with SFT models and ChatGPT. The absence of open-source implementations has posed significant challenges to the investigation of LLMs alignment. Therefore, we are eager to release technical reports, reward models and PPO code

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation

Asthma susceptible genes in Chinese population: A meta-analysis

<p>Abstract</p> <p>Background</p> <p>Published data regarding the associations between genetic variants and asthma risk in Chinese population were inconclusive. The aim of this study was to investigate asthma susceptible genes in Chinese population.</p> <p>Methods</p> <p>The authors conducted 18 meta-analyzes for 18 polymorphisms in 13 genes from eighty-two publications.</p> <p>Results</p> <p>Seven polymorphisms were found being associated with risk of asthma, namely: <it>A Disintegrin and Metalloprotease 33 </it>(<it>ADAM33</it>) T1-C/T (odds ratio [OR] = 6.07, 95% confidence interval [CI]: 2.69-13.73), <it>Angiotensin-Converting Enzyme </it>(<it>ACE</it>) D/I (OR = 3.85, 95%CI: 2.49-5.94), <it>High-affinity IgE receptor β chain </it>(<it>FcεRIβ</it>) -6843G/A (OR = 1.49, 95%CI: 1.01-2.22), <it>Interleukin 13</it>(<it>IL-13</it>) -1923C/T (OR = 2.99, 95%CI: 2.12-4.24), <it>IL-13 </it>-2044A/G (OR = 1.49, 95%CI: 1.07-2.08), <it>Regulated upon Activation, Normal T cell Expressed and Secreted </it>(<it>RANTES</it>) -28C/G (OR = 1.64, 95%CI: 1.09-2.46), <it>Tumor Necrosis Factor-α </it>(<it>TNF-α</it>) -308G/A(OR = 1.42, 95%CI: 1.09, 1.85). After subgroup analysis by age, the <it>ACE </it>D/I, <it>β2-Adrenergic Receptor </it>(<it>β2-AR</it>) -79G/C, <it>TNF-α </it>-308G/A, <it>Interleukin 4 receptor</it>(<it>IL-4R</it>) -1902G/A and <it>IL-13 </it>-1923C/T polymorphisms were found significantly associated with asthma risk in Chinese children. In addition, the <it>ACE </it>D/I, <it>FcεRIβ </it>-6843G/A, <it>TNF-α </it>-308G/A, <it>IL-13 </it>-1923C/T and <it>IL-13 </it>-2044A/G polymorphisms were associated with asthma risk in Chinese adults.</p> <p>Conclusion</p> <p><it>ADAM33, FcεRIβ, RANTES, TNF-α, ACE, β2-AR, IL-4R </it>and <it>IL-13 </it>genes could be proposed as asthma susceptible genes in Chinese population. Given the limited number of studies, more data are required to validate these associations.</p

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

Collaborating Filtering Community Image Recommendation System Based on Scene

With the advancement of smart city, the development of intelligent mobile terminal and wireless network, the traditional text information service no longer meet the needs of the community residents, community image service appeared as a new media service. “There are pictures of the truth” has become a community residents to understand and master the new dynamic community, image information service has become a new information service. However, there are two major problems in image information service. Firstly, the underlying eigenvalues extracted by current image feature extraction techniques are difficult for users to understand, and there is a semantic gap between the image content itself and the user’s understanding; secondly, in community life of the image data increasing quickly, it is difficult to find their own interested image data. Aiming at the two problems, this paper proposes a unified image semantic scene model to express the image content. On this basis, a collaborative filtering recommendation model of fusion scene semantics is proposed. In the recommendation model, a comprehensiveness and accuracy user interest model is proposed to improve the recommendation quality. The results of the present study have achieved good results in the pilot cities of Wenzhou and Yan'an, and it is applied normally