Modulation of Gut Microbiota in Pathological States

The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract (GIT). Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease (NAFLD); obesity and diabetes, which are characterized as “lifestyle diseases” of the industrialized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the reader with an updated overview of the importance of the gut microbiota for human health and the potential to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile (C. difficile) infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial microbes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future

We know what you want to buy:a demographic-based system for product recommendation on microblogs

Product recommender systems are often deployed by e-commerce websites to improve user experience and increase sales. However, recommendation is limited by the product information hosted in those e-commerce sites and is only triggered when users are performing e-commerce activities. In this paper, we develop a novel product recommender system called METIS, a MErchanT Intelligence recommender System, which detects users' purchase intents from their microblogs in near real-time and makes product recommendation based on matching the users' demographic information extracted from their public profiles with product demographics learned from microblogs and online reviews. METIS distinguishes itself from traditional product recommender systems in the following aspects: 1) METIS was developed based on a microblogging service platform. As such, it is not limited by the information available in any specific e-commerce website. In addition, METIS is able to track users' purchase intents in near real-time and make recommendations accordingly. 2) In METIS, product recommendation is framed as a learning to rank problem. Users' characteristics extracted from their public profiles in microblogs and products' demographics learned from both online product reviews and microblogs are fed into learning to rank algorithms for product recommendation. We have evaluated our system in a large dataset crawled from Sina Weibo. The experimental results have verified the feasibility and effectiveness of our system. We have also made a demo version of our system publicly available and have implemented a live system which allows registered users to receive recommendations in real time

Changes in soil chemical properties as affected by pyrogenic organic matter amendment with different intensity and frequency

Pyrogenic organicmatter (PyOM) has long been used as a soil amendment to improve soil physicochemical properties. However, few studies simultaneously investigated both intensities and frequencies of PyOM addition on soil chemical properties of soil base cations, soil pHbuffering capacity (pHBC), and plant availablemicronutrients. In the main food production area of lower Liaohe River Plain in Northeast China, a field manipulation of PyOM addition was initiated in 2013 to examine how the intensities (0, 1%, 3%, and 5% of 0-20 cm soil mass) and frequencies (3% of soil mass applied once versus yearly for 3 years) of PyOM amendment affected soil chemical properties. Higher intensity of PyOM addition significantly increased soil exchangeable Mg (by 24.2%), which was caused by increase of soil pH, soil exchangeable surfaces, and soil organic matter. Plant available Fe, Mn, and Cu were significantly decreased with increasing PyOM addition intensity by up to 39.4%, 50.8%, and 30.0%, respectively, especially under the highest amount of PyOM amendment (5%). This was possibly due to removal of micronutrients with plant biomass or irreversible binding of available micronutrients on PyOM which decreased the extraction efficiency. Under the same amount of PyOM addition (3% in total), higher frequency of PyOM amendment significantly increased soil exchangeable Mg, while lower frequency showed no impact as compared to control plots (CK). Higher frequency of PyOM amendment significantly decreased plant available Mn and Cu as compared to both lower frequency and CK treatments. Both the intensity and frequency of PyOMaddition significantly increased soil pH but showed no influence on soil pHBC. Our results showed that exchangeableMg increased but availableMn and Cu decreasedwith both PyOMamendment intensity and frequency. Even though PyOM amendment could enrich soil base cations, it might cause deficiency of available micronutrients and pose a threat to plant productivity in agroecosystems

The mechanisms crosstalk and therapeutic opportunities between ferroptosis and ovary diseases

Ferroptosis, a form of regulated cell death, was first defined in 2012. Ferroptosis mainly involves iron-driven lipid peroxidation damage of cells. This process is regulated by iron homeostasis, redox balance, lipid metabolism, glutathione metabolism, and various disease signaling pathways. Iron is one of the key mineral elements that regulate the physiological function of women and the development of ovarian tumors. Occurrence of Ferroptosis has some hidden dangers and advantages in ovary diseases. Some scholars have shown that ferroptosis of ovarian granulosa cells (GC) promotes the development of ovarian dysfunction and polycystic ovary syndrome (PCOS). Interestingly, drug-resistant ovarian cancer cells are very sensitive to ferroptosis, suggesting that pharmacological positive and negative regulation of ferroptosis has great potential in the treatment of benign ovarian diseases and ovarian cancer. This article aimed to assess how ferroptosis occurs and the factors controlling ferroptosis. Moreover, we summarize how ferroptosis can be used to predict, diagnose and target treatment ovary disease. Meanwhile, we also evaluated the different phenomena of Ferroptosis in ovarian diseases. It aims to provide new directions for the research and prevention of female reproductive diseases

Current status and progress in research on dressing management for diabetic foot ulcer

Diabetic foot ulcer (DFU) is a major complication of diabetes and is associated with a high risk of lower limb amputation and mortality. During their lifetime, 19%–34% of patients with diabetes can develop DFU. It is estimated that 61% of DFU become infected and 15% of those with DFU require amputation. Furthermore, developing a DFU increases the risk of mortality by 50%–68% at 5 years, higher than some cancers. Current standard management of DFU includes surgical debridement, the use of topical dressings and wound decompression, vascular assessment, and glycemic control. Among these methods, local treatment with dressings builds a protective physical barrier, maintains a moist environment, and drains the exudate from DFU wounds. This review summarizes the development, pathophysiology, and healing mechanisms of DFU. The latest research progress and the main application of dressings in laboratory and clinical stage are also summarized. The dressings discussed in this review include traditional dressings (gauze, oil yarn, traditional Chinese medicine, and others), basic dressings (hydrogel, hydrocolloid, sponge, foam, film agents, and others), bacteriostatic dressings, composite dressings (collagen, nanomaterials, chitosan dressings, and others), bioactive dressings (scaffold dressings with stem cells, decellularized wound matrix, autologous platelet enrichment plasma, and others), and dressings that use modern technology (3D bioprinting, photothermal effects, bioelectric dressings, microneedle dressings, smart bandages, orthopedic prosthetics and regenerative medicine). The dressing management challenges and limitations are also summarized. The purpose of this review is to help readers understand the pathogenesis and healing mechanism of DFU, help physicians select dressings correctly, provide an updated overview of the potential of biomaterials and devices and their application in DFU management, and provide ideas for further exploration and development of dressings. Proper use of dressings can promote DFU healing, reduce the cost of treating DFU, and reduce patient pain

A feasibility study of multi-electrode high-purity germanium detector for Ge-76 neutrinoless double beta decay searching

Experiments to search for neutrinoless double-beta (0{\nu}\b{eta}\b{eta}) decay of 76Ge using a high-purity germanium (HPGe) detector rely heavily on background suppression technologies to enhance their sensitivities. In this work, we proposed a pulse-shape analysis method based on a neural network (NN) and a light gradient boosting machine (lightGBM; LGB) to discriminate single-electron (background) and double-electrons (0{\nu}\b{eta}\b{eta} signal) events in a multi-electrode HPGe detector. In this paper, we describe a multi-electrode HPGe detector system, a data-processing system, and pulse-shape simulation procedures. We built a fully connected (FC) neural network and an LGB model to classify the single- and double-electron events. The FC network is trained with simulated single- and double-electron-induced pulses and tested in an independent dataset generated by the pulse-shape simulation. The discrimination efficiency of the FC neural network in the test set for the 0{\nu}\b{eta}\b{eta} double-electron events signal was 77.4%, the precision was 57.7%, and the training time was 430 min. The discrimination efficiency of LGB model was 73.1%, the precision was 64.0%, and the training time was 1.5 min. This study demonstrated that it is feasible to realize single- and double-electron discrimination on multi-electrode HPGe detectors using an FC neural network and LGB model. These results can be used as a reference for future 76Ge 0{\nu}\b{eta}\b{eta} experiments.Comment: 16 pages,12 figure

Lower-Molecular-Weight Chitosan-Treated Polyethyleneimine: a Practical Strategy For Gene Delivery to Mesenchymal Stem Cells

Background/Aims: Genetic modification of mesenchymal stem cells (MSCs) is an essential requirement for their use as a delivery vehicle. To achieve higher transfection efficiency and better reproducibility than previously synthesized chitosan (100 kDa)-polyethylenimine (PEI; 1200 Da), we synthesized a low molecular weight PEI (1200 Da)-grafted chitosan (50 kDa) (CP). Methods: Safety of CP/DNA or PEI (25 kDa)/DNA was evaluated by an MTT assay using A549 cells or MSCs and a zebrafish embryo model. Effects of CP/DNA on the characteristics of MSCs were evaluated using flow cytometry. Additionally, a pGL3 plasmid was used to investigate the transfection efficiency of PEI (25 kDa), chitosan (100 kDa)-PEI (1200 Da), and CP with different N/P mass ratios on A549 cells and MSCs. Furthermore, CP/pGL3 was used to investigate the effect of serum on transfection, and intracellular transport was assessed by observing the intracellular location of DNA using laser scanning confocal microscopy. In addition, the effect of endocytosis on transfection efficiency was evaluated using A549 cells pre-treated with different inhibitors. Investigations related to analysis of transfection efficiency were all performed using the BCA protein assay to standardize the data. Furthermore, TGF-β1-and CXCR4-expressing plasmids were applied to evaluate the gene transfer efficiency of CP, including its effects on the osteogenic differentiation and migratory ability of MSCs. Results: The safety evaluation demonstrated that CP/DNA had significantly lower toxicity than PEI (25 kDa)/DNA. Additionally, DNA entered MSCs transfected by CP without changing their properties, while the examination of intracellular transport demonstrated that CP/pGL3 was internalized rapidly into MSCs. Furthermore, studies of the internalization mechanism showed that CP/pGL3 complexes entered the cells through caveolae-mediated endocytosis, thereby suggesting that the CP coating helped DNA enter A549 cells without the requirement for receptors. Compared to PEI (25 kDa), the interference of serum on transfection was reduced significantly with the use of CP in both A549 cells and MSCs. To evaluate the effects of gene delivery using the constructed CP complex and the possibility of obtaining gene-engineered MSCs, TGF-β1- and CXCR4-expressing plasmids were successfully delivered into MSCs, confirming their ability to induce osteogenesis and change the migratory ability of MSCs, respectively. Conclusion: These results demonstrated that CP could be used to deliver genes into MSCs and could potentially be used in gene therapy based on MSCs

Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus’s clinical applications

Effects of Simulated Microgravity on Embryonic Stem Cells

There have been many studies on the biological effects of simulated microgravity (SMG) on differentiated cells or adult stem cells. However, there has been no systematic study on the effects of SMG on embryonic stem (ES) cells. In this study, we investigated various effects (including cell proliferation, cell cycle distribution, cell differentiation, cell adhesion, apoptosis, genomic integrity and DNA damage repair) of SMG on mouse embryonic stem (mES) cells. Mouse ES cells cultured under SMG condition had a significantly reduced total cell number compared with cells cultured under 1 g gravity (1G) condition. However, there was no significant difference in cell cycle distribution between SMG and 1G culture conditions, indicating that cell proliferation was not impaired significantly by SMG and was not a major factor contributing to the total cell number reduction. In contrast, a lower adhesion rate cultured under SMG condition contributed to the lower cell number in SMG. Our results also revealed that SMG alone could not induce DNA damage in mES cells while it could affect the repair of radiation-induced DNA lesions of mES cells. Taken together, mES cells were sensitive to SMG and the major alterations in cellular events were cell number expansion, adhesion rate decrease, increased apoptosis and delayed DNA repair progression, which are distinct from the responses of other types of cells to SMG