A modular toolkit for environmental , , and enables complex metabolic manipulation.

Soil-dwelling Actinomycetes are a diverse and ubiquitous component of the global microbiome but largely lack genetic tools comparable to those available in model species such as or , posing a fundamental barrier to their characterization and utilization as hosts for biotechnology. To address this, we have developed a modular plasmid assembly framework, along with a series of genetic control elements for the previously genetically intractable Gram-positive environmental isolate C208, and demonstrate conserved functionality in 11 additional environmental isolates of , , and . This toolkit encompasses five Mycobacteriale origins of replication, five broad-host-range antibiotic resistance markers, transcriptional and translational control elements, fluorescent reporters, a tetracycline-inducible system, and a counter-selectable marker.

Interrogating the Function of Bicistronic Translational Control Elements to Improve Consistency of Gene Expression.

Context independent gene expression is required for genetic circuits to maintain consistent and predicable behavior. Previous efforts to develop context independent translation have leveraged the helicase activity of translating ribosomes via bicistronic design translational control elements (BCDs) located within an efficiently translated leader peptide. We have developed a series of bicistronic translational control elements with strengths that span several orders of magnitude, maintain consistent expression levels across diverse sequence contexts, and are agnostic to common ligation sequences used in modular cloning systems.

Effects of CYP3A43 Expression on Cell Proliferation and Migration of Lung Adenocarcinoma and Its Clinical Significance.

The cytochrome P450s (CYP450s) include key oxidative enzymes involved in the metabolism of various carcinogens and anticancer drugs. Bioinformatic studies have demonstrated the association of CYP3A43 with liver cancer and ovarian cancer. However, the biological function of CYP3A43 in tumor progression remains unclear.

Transcriptional upregulation of MAPK15 by NF-κB signaling boosts the efficacy of combination therapy with cisplatin and TNF-α.

The efficacy of cisplatin in treating advanced non-small cell lung cancer is limited mainly because of insensitivity and/or acquired resistance. MAPK15, previously shown by us to enhance the sensitivity of the anti-cancer drug arsenic trioxide, could also enhance the sensitivity of other anti-cancer drugs. Here, we explore the potential role of MAPK15 in chemosensitivity to cisplatin in human lung cancer cells.

A postpartum enriched environment rescues impaired cognition and oxidative markers in aged mice with gestational inflammation.

Introduction: Previous studies have shown that gestational inflammation can accelerate age-associated cognitive decline (AACD) in maternal mice; enriched environments (EEs) have been reported to protect normally aging mice from AACD and improve mitochondrial function. However, it is unclear whether the nitrosative stress-related proteins tet methylcytosine dioxygenase 1 (TET1) and S-nitrosoglutathione reductase (GSNOR) are involved in the accelerated aging process of gestational inflammation and whether EEs can slow this process.

Methods: In this study, CD-1 female mice on the 15th day of pregnancy were injected with bacterial lipopolysaccharide (50 μg/kg; LPS group) or an equivalent amount of normal saline (CON group) from the abdominal cavity for 4 consecutive days.

Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway.

Cytochrome P450 enzymes (CYP450s) exert mighty catalytic actions in cellular metabolism and detoxication, which play pivotal roles in cell fate determination. Preliminary data shows differential expression levels of CYP27C1, one of the "orphan P450s" in human lung cancer cell lines. Here, we study the functions of CYP27C1 in lung cancer progression and drug endurance, and explore its potential to be a diagnostic and therapeutic target for lung cancer management.

ACC2 is under-expressed in lung adenocarcinoma and predicts poor clinical outcomes.

Purpose: Acetyl-CoA Carboxylases (ACCs) are key fatty acid metabolic enzymes responsible for catalyzing the carboxylation of acetyl-CoA to malonyl-CoA. The role of ACC1 has been associated with tumor biology, but the role of ACC2 in cancer remains largely uncharacterized.

Methods: We conducted a transcriptomic analysis using GEPIA and Oncomine to study the expression of ACC2 in different cancers.

Predictive Value of Red Blood Cell Distribution Width in Poststroke Depression.

Purpose: Red blood cell distribution width (RDW) is increased in a variety of inflammatory-related diseases. However, there is no report of its clinical significance in poststroke depression (PSD). This study explores the clinical significance of RDW in PSD patients.

S,S-Tetrazine-Based Hydrogels with Visible Light Cleavable Properties for On-Demand Anticancer Drug Delivery.

Photocleavable hydrogels are of great importance in the field of controlled drug delivery, stem cell fate regulation, surface patterning, and intelligent devices. However, the development of novel photocleavable gel systems by visible light is usually met with challenges such as the lack of efficient and tunable photocleavable groups and reactions. Herein, we reported the facile fabrication of a new type of photocleavable hydrogels by the direct gelation of 4-arm thiol-terminated polyethylene glycol with 3,6-dichloro-1,2,4,5-tetrazine the formation of S,S-tetrazine linkages.

Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies.

Conventional chemotherapy is still an important option of cancer treatment, but it has poor cell selectivity, severe side effects, and drug resistance. Utilizing nanoparticles (NPs) to improve the therapeutic effect of chemotherapeutic drugs has been highlighted in recent years. Nanotechnology dramatically changed the face of oncology by high loading capacity, less toxicity, targeted delivery of drugs, increased uptake to target sites, and optimized pharmacokinetic patterns of traditional drugs.

Potency and Selectivity of SMAC/DIABLO Mimetics in Solid Tumor Therapy.

Aiming to promote cancer cell apoptosis is a mainstream strategy of cancer therapy. The second mitochondria-derived activator of caspase (SMAC)/direct inhibitor of apoptosis protein (IAP)-binding protein with low pI (DIABLO) protein is an essential and endogenous antagonist of inhibitor of apoptosis proteins (IAPs). SMAC mimetics (SMs) are a series of synthetically chemical compounds.

[Development and application of optogenetic tools].

Dynamic variations of the cell microenvironment can affect cell differentiation, cell signaling pathways, individual growth, and disease. Optogenetics combines gene-encoded protein expression with optical controlling, and offers a novel, reversible, non-invasive and spatiotemporal-specific research tool to dynamically or reversibly regulate cell signaling pathways, subcellular localization and gene expression. This review summarizes the types of optogenetic components and the involved cellular signaling pathways, and explores the application and future prospects of the light-controlled cell signaling pathways.

Phytofabrication of Nanoparticles as Novel Drugs for Anticancer Applications.

Cancer is one of the foremost causes of death globally and also the major stumbling block of increasing life expectancy. Although the primary treatment of surgical resection, chemotherapy, and radiotherapy have greatly reduced the mortality of cancer, the survival rate is still low because of the metastasis of tumor, a range of adverse drug reactions, and drug resistance. For all this, it is relevant to mention that a growing amount of research has shown the anticarcinogenic effect of phytochemicals which can modulate the molecular pathways and cellular events include apoptosis, cell proliferation, migration, and invasion.