A digital CRISPR-dCas9-based gene remodeling biocomputer programmed by dietary compounds in mammals.

CRISPR-dCas9 (dead Cas9 protein) technology, combined with chemical molecules and light-triggered genetic switches, offers customizable control over gene perturbation. However, these simple ON/OFF switches cannot precisely determine the sophisticated perturbation process. Here, we developed a resveratrol and protocatechuic acid-programmed CRISPR-mediated gene remodeling biocomputer (REPA) for conditional endogenous transcriptional regulation of genes in vitro and in vivo.

3D FRP Reinforcement Systems for Concrete Beams: Innovation towards High Performance Concrete Structures.

Despite the advantages of using lightweight and non-corrosive carbon fiber reinforced polymer (CFRP) reinforcements in concrete structures, their widespread adoption has been limited due to concerns regarding the brittle failure of CFRP rupture and its relatively softer load-deflection stiffness. This work offers logical solutions to these two crucial problems: using aggregate coating to strengthen the CFRP-concrete bond and ultimately the load-deflection stiffness, and using CFRP-concrete debonding propagation to create pseudo-ductile behavior. Subsequently, the concrete cracking behavior, the apparent CFRP modulus with aggregates, and the post-peak capacity and deflection of three-dimensional (3D) CFRP-reinforced concrete are all described by equations derived from experiments.

Exploring plant-derived phytochrome chaperone proteins for light-switchable transcriptional regulation in mammals.

Synthetic biology applications require finely tuned gene expression, often mediated by synthetic transcription factors (sTFs) compatible with the human genome and transcriptional regulation mechanisms. While various DNA-binding and activation domains have been developed for different applications, advanced artificially controllable sTFs with improved regulatory capabilities are required for increasingly sophisticated applications. Here, in mammalian cells and mice, we validate the transactivator function and homo-/heterodimerization activity of the plant-derived phytochrome chaperone proteins, FHY1 and FHL.

Di-(2-ethylhexyl) phthalate (DEHP) promoted hepatic lipid accumulation by activating Notch signaling pathway.

Di-(2-ethylhexyl) phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) can induce hepatic lipid metabolism disorders, while the molecular mechanism still remain unknown. We aim to explore the underlying mechanism of Notch signaling pathway on hepatic lipid accumulation induced by DEHP/MEHP. A total of 40 male wistar rats were exposed to DEHP (0, 5, 50, and 500 mg/kg/d) for 8 weeks, BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100, and 200 μM) for 24 h.

Nanoplastics and Microplastics May Be Damaging Our Livers.

Plastics in the environment can be degraded and even broken into pieces under the action of natural factors, and the degraded products with a particle size of less than 5 mm are called microplastics (MPs). MPs exist in a variety of environmental media that come into contact with the human body. It can enter the body through environmental media and food chains.

Effect of Acute Cold Exposure on Energy Metabolism and Activity of Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis.

The benefit of cold exposure for humans against obesity has brought the energy metabolism and activity of brown adipose tissue (BAT) induced by cold into focus. But the results are inconsistent. This review is aimed to systematically explore the effect of cold exposure on the activity of BAT and energy metabolism in humans.

The Relationship Between Colorectal Polyps and Serum Lipid Levels: A Systematic Review and Meta-analysis.

Colorectal polyp has been considered as the precancerous lesion of colorectal cancer, to which serum lipid levels are closely related. At present, there is no consensus on the relationship between colorectal polyps and serum lipid levels. We performed a meta-analysis to explore the effects of lipid levels on colorectal polyps.

A far-red light-inducible CRISPR-Cas12a platform for remote-controlled genome editing and gene activation.

The CRISPR-Cas12a has been harnessed as a powerful tool for manipulating targeted gene expression. The possibility to manipulate the activity of CRISPR-Cas12a with a more precise spatiotemporal resolution and deep tissue permeability will enable targeted genome engineering and deepen our understanding of the gene functions underlying complex cellular behaviors. However, currently available inducible CRISPR-Cas12a systems are limited by diffusion, cytotoxicity, and poor tissue permeability.

Role of miR-145-5p/ CD40 in the inflammation and apoptosis of HUVECs induced by PM.

Fine particulate matter (PM) exposure can cause the injury of vascular endothelial cells by inflammatory response. CD40 works in inflammation of endothelial cells and it may be regulated by the miRNAs. This study aimed to clarify the role and mechanism of CD40 and miR-145-5p in PM-induced injury of human umbilical vein endothelial cells (HUVECs).

Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control.

Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice.

Relationships between di-(2-ethylhexyl) phthalate exposure and lipid metabolism in adolescents: Human data and experimental rat model analyses.

In recent years, the incidence of lipid metabolism disorders in adolescents has gradually increased, and the effects of DEHP on lipid metabolism have received widespread attention. In this study, 463 adolescents aged 16-19 years were enrolled as subjects. This study analyzed the associations between the urinary levels of DEHP metabolites (MEHP, MEOHP, MEHHP, MECPP, MCMHP, and ∑DEHP) and BMI, WHR, WtHR, VAI, LAP, the plasma levels of lipids (TC, TG, HDL-C, and LDL-C), and the peripheral blood leukocyte mRNA levels of SREBP-2, SR-BI, LDLR, and NR1H3.

Engineering genetic devices for in vivo control of therapeutic T cell activity triggered by the dietary molecule resveratrol.

Chimeric antigen receptor (CAR)-engineered T cell therapies have been recognized as powerful strategies in cancer immunotherapy; however, the clinical application of CAR-T is currently constrained by severe adverse effects in patients, caused by excessive cytotoxic activity and poor T cell control. Herein, we harnessed a dietary molecule resveratrol (RES)-responsive transactivator and a transrepressor to develop a repressible transgene expression (RES) device and an inducible transgene expression (RES) device, respectively. After optimization, these tools enabled the control of CAR expression and CAR-mediated antitumor function in engineered human cells.

MUC5B regulates the airway inflammation induced by atmospheric PM in rats and A549 cells.

Atmospheric PM can induce airway inflammation and mucin secretion. MUC5B is required for airway defense. However, the research on the role of MUC5B in airway inflammation induced by atmospheric PM remains limited.

A green tea-triggered genetic control system for treating diabetes in mice and monkeys.

Cell-based therapies are recognized as the next frontier in medicine, but the translation of many promising technologies into the clinic is currently limited by a lack of remote-control inducers that are safe and can be tightly regulated. Here, we developed therapeutically active engineered cells regulated by a control system that is responsive to protocatechuic acid (PCA), a metabolite found in green tea. We constructed multiple genetic control technologies that could toggle a PCA-responsive ON/OFF switch based on a transcriptional repressor from We demonstrated that PCA-controlled switches can be used for guide RNA expression-mediated control of the CRISPR-Cas9 systems for gene editing and epigenetic remodeling.

Resveratrol reduces the inflammatory response in adipose tissue and improves adipose insulin signaling in high-fat diet-fed mice.

Background: Obesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused by a high-fat diet (HFD) in mice.

[Research progress of mammalian synthetic biology in biomedical field].

Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct gene circuits uploaded into living cells or organisms to perform novel or improved functions, and it has been widely used in many fields. In this review, we describe the recent advances of mammalian synthetic biology for the treatment of diseases.

Self-adjusting synthetic gene circuit for correcting insulin resistance.

By using tools from synthetic biology, sophisticated genetic devices can be assembled to reprogram mammalian cell activities. Here, we demonstrate that a self-adjusting synthetic gene circuit can be designed to sense and reverse the insulin-resistance syndrome in different mouse models. By functionally rewiring the mitogen-activated protein kinase (MAPK) signalling pathway to produce MAPK-mediated activation of the hybrid transcription factor TetR-ELK1, we assembled a synthetic insulin-sensitive transcription-control device that self-sufficiently distinguished between physiological and increased blood insulin levels and correspondingly fine-tuned the reversible expression of therapeutic transgenes from synthetic TetR-ELK1-specific promoters.

Smartphone-controlled optogenetically engineered cells enable semiautomatic glucose homeostasis in diabetic mice.

With the increasingly dominant role of smartphones in our lives, mobile health care systems integrating advanced point-of-care technologies to manage chronic diseases are gaining attention. Using a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology, we have engineered a technological infrastructure enabling the smartphone-assisted semiautomatic treatment of diabetes in mice. A custom-designed home server SmartController was programmed to process wireless signals, enabling a smartphone to regulate hormone production by optically engineered cells implanted in diabetic mice via a far-red light (FRL)-responsive optogenetic interface.

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes.

Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients.

[Simulation research of respiratory monitoring with magnetic detection electrical impedance tomography].

In order to explore the feasibility of applying magnetic detection electrical impedance tomography(MDEIT) on respiratory monitoring, aiming at the forward problem of magnetic detection electrical impedance tomography, we calculated the electric potential and current density distribution inside the imaging object by using the finite element method. We then got magnetic induction intensity outside the object at the end of exhaling and inhaling according to Biot-Savart’s law. The results showed that the magnetic induction intensity at the end of inhaling was 8.

Physiological responses to Nilaparvata lugens in susceptible and resistant rice varieties: allocation of assimilates between shoots and roots.

Nilaparvata lugens (Stål) is a typical vascular feeder, primarily sucking the phloem sap of host plants. Its feeding on rice, Oryza sativa L., plants changes the pattern of allocation of assimilates between roots and shoots, and the root:shoot (R/S) ratio of assimilates is often measured as an index of physiological responses to N.

Cultivar and insecticide applications affect the physiological development of the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae).

Nilaparvata lugens (Stål) (Hemiptera:Delphacidae) is a serious migratory pest of rice in Asia. Pest resurgence often occurs because of insecticide overuse. Using both susceptible (TN1) and moderately resistant (Xieyou 963) cultivars, we studied the effect of foliar insecticides on the percentage of brachypterous adults, female reproductive rate, and crude fat and soluble sugar contents in third- and fifth-instar nymphs and adults.