CRISPR Screening and Comparative LC-MS Analysis Identify Genes Mediating Efficacy of Delamanid and Pretomanid against Mycobacterium tuberculosis.

Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical-genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance.

Surgical management of pituitary adenoma during pregnancy.

Background: Although conservative treatment is typically recommended for pregnant patients with pituitary adenoma (PA), surgical treatment is occasionally necessary for those with acute symptoms. Currently, surgical interventions utilized among these patients is poorly studied.

Aim: To evaluate the surgical indications, timing, perioperative precautions and postoperative complications of PAs during pregnancy and to provide comprehensive guidance.

A frameshift in alters canonical Rcs signalling to preserve flea-mammal plague transmission cycles.

Multiple genetic changes in the enteric pathogen have driven the emergence of , the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenization of , encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating flea-borne transmission.

Application of combined CRISPR screening for genetic and chemical-genetic interaction profiling in .

CRISPR screening, including CRISPR interference (CRISPRi) and CRISPR-knockout (CRISPR-KO) screening, has become a powerful technology in the genetic screening of eukaryotes. In contrast with eukaryotes, CRISPR-KO screening has not yet been applied to functional genomics studies in bacteria. Here, we constructed genome-scale CRISPR-KO and also CRISPRi libraries in (Mtb).

A Series of Efficient Umbrella Modeling Strategies to Track Irradiation-Mutation Strains Improving Butyric Acid Production From the Pre-development Earlier Stage Point of View.

() is a fermentation strain used to produce butyric acid. A promising new biofuel, n-butanol, can be produced by catalysis of butyrate, which can be obtained through microbial fermentation. Butyric acid has various uses in food additives and flavor agents, antiseptic substances, drug formulations, and fragrances.

Response characteristics of the membrane integrity and physiological activities of the mutant strain Y217 under exogenous butanol stress.

Butanol inhibits bacterial activity by destroying the cell membrane of Clostridium acetobutylicum strains and altering functionality. Butanol toxicity also results in destruction of the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS), thereby preventing glucose transport and phosphorylation and inhibiting transmembrane transport and assimilation of sugars, amino acids, and other nutrients. In this study, based on the addition of exogenous butanol, the tangible macro indicators of changes in the carbon ion beam irradiation-mutant Y217 morphology were observed using scanning electron microscopy (SEM).

A CRISPR-Assisted Nonhomologous End-Joining Strategy for Efficient Genome Editing in Mycobacterium tuberculosis.

New tools for genetic manipulation of are needed for the development of new drug regimens and vaccines aimed at curing tuberculosis infections. Clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) systems generate a highly specific double-strand break at the target site that can be repaired via nonhomologous end joining (NHEJ), resulting in the desired genome alteration. In this study, we first improved the NHEJ repair pathway and developed a CRISPR-Cas-mediated genome-editing method that allowed us to generate markerless deletion in , , and Then, we demonstrated that this system could efficiently achieve simultaneous generation of double mutations and large-scale genetic mutations in Finally, we showed that the strategy we developed can also be used to facilitate genome editing in The global health impact of necessitates the development of new genetic tools for its manipulation, to facilitate the identification and characterization of novel drug targets and vaccine candidates.

MicroRNA-143-5p targeting eEF2 gene mediates intervertebral disc degeneration through the AMPK signaling pathway.

Background: Intervertebral disc degeneration (IDD) is a major contributor to back, neck, and radicular pain, and the treatment of IDD is costly and relatively ineffective. Dysregulation of microRNAs (miRNAs) has been reported to be involved in IDD. The purpose of our study is to illustrate the potential that miR-143-5p targeting eEF2 gene mediates IDD.

Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China.

Objectives: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study.

Subjects And Methods: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery.

AU-Rich Long 3' Untranslated Region Regulates Gene Expression in Bacteria.

3' untranslated regions (3' UTRs) and particularly long 3' UTRs have been shown to act as a new class of post-transcriptional regulatory element. We previously reported that mRNA stability is negatively regulated by the 3' UTR of in . To investigate more general effects of 3' UTRs in , we selected 15 genes potentially possessing long 3' UTRs with different AU content and constructed their 3' UTR deletion mutants.

NFAT5 up-regulates expression of the kidney-specific ubiquitin ligase gene under hypertonic conditions in inner-medullary collecting duct cells.

We previously reported that among the 37 RING finger protein (RNF) family members, mRNA is specifically expressed in the kidney under normal conditions. However, the mechanism supporting its kidney-specific expression pattern remains unclear. In this study, we elucidated the mechanism of the transcriptional activation of murine in inner-medullary collecting duct cells.

Multiview fringe matching profilometry in a projector-camera system.

This Letter proposes a novel approach, called multiview fringe matching profilometry (MFMP), for three-dimensional (3D) measurement in a projector-camera system. An essential difference from the traditional optical profilometries in our MFMP test is that a projector will be regarded as a camera with the reverse lightpath and not just as a coding projection device. Therefore, profiting by a maximum utilization of a multiview matching relationship, the homonymy points can be directly found with the geometric constraint of the corresponding fringe images between the projector and cameras.

Corrigendum: HmsC Controls Biofilm Formation in Response to Redox Environment.

[This corrects the article on p. 355 in vol. 7, PMID: 28848715.

Sec16A, a key protein in COPII vesicle formation, regulates the stability and localization of the novel ubiquitin ligase RNF183.

We identified 37 ubiquitin ligases containing RING-finger and transmembrane domains. Of these, we found that RNF183 is abundantly expressed in the kidney. RNF183 predominantly localizes to the endoplasmic reticulum (ER), Golgi, and lysosome.

New Insights into the Non-orthodox Two Component Rcs Phosphorelay System.

The Rcs phosphorelay system, a non-orthodox two-component regulatory system, integrates environmental signals, regulates gene expression, and alters the physiological behavior of members of the Enterobacteriaceae family of Gram-negative bacteria. Recent studies of Rcs system focused on protein interactions, functions, and the evolution of Rcs system components and its auxiliary regulatory proteins. Herein we review the latest advances on the Rcs system proteins, and discuss the roles that the Rcs system plays in the environmental adaptation of various Enterobacteriaceae species.

Short-Term Outcomes of Open Reduction and Internal Fixation for Sanders Type III Calcaneal Fractures With and Without Bone Grafts.

Calcaneal fractures, often caused by a fall from a height, are the most common injuries encountered by orthopedic surgeons. Currently, open anatomic reduction and internal fixation (ORIF) is considered a valuable treatment of displaced intraarticular fractures of the calcaneus; however, the need for bone grafting in the treatment is still controversial. Therefore, in the present study, we investigated the outcomes of 2 methods (with and without bone grafting) used for the surgical treatment of Sanders type III calcaneal fractures.

Inhibitory effect of curcumin in human endometriosis endometrial cells via downregulation of vascular endothelial growth factor.

Endometriosis, which affects up to 10% of women of reproductive age, is defined as endometrial-like gland and stroma tissue growths outside the uterine cavity. Despite increasing research efforts, there are no current effective treatment methods for this disease, therefore investigations for therapeutic strategies are of primary concern. In preliminary work, the authors demonstrated that curcumin inhibits endometriosis in vivo.

HmsC Controls Biofilm Formation in Response to Redox Environment.

biofilm formation, controlled by intracellular levels of the second messenger molecule cyclic diguanylate (c-di-GMP), is important for blockage-dependent plague transmission from fleas to mammals. HmsCDE is a tripartite signaling system that modulates intracellular c-di-GMP levels to regulate biofilm formation in . Previously, we found that biofilm formation is stimulated in reducing environments in an -dependent manner.

Regulatory 3' Untranslated Regions of Bacterial mRNAs.

The untranslated regions (UTRs) of mRNA contain important features that are relevant to the post-transcriptional and translational regulation of gene expression. Most studies of bacterial UTRs have focused on the 5'regions; however, 3'UTRs have recently emerged as a new class of post-transcriptional regulatory elements. 3'UTRs were found to regulate the decay and translation initiation in their own mRNAs.

Adenovirus-mediated bone morphogenetic protein-2 promotes osteogenic differentiation in human mesenchymal stem cells .

Delayed and failed bone union following fracture is a common clinical complication that requires treatment in orthopedics. Cell-based therapies and tissue-engineering approaches are potential therapeutic strategies for bone repair and fracture healing. However, the effect of adenovirus expressing bone morphogenetic protein-2 (Ad-BMP-2) on the osteogenic ability of human mesenchymal stem cells (hMSCs) has remained to be fully elucidated.

[Association of GH and IGF-1 Burden with Cardiac Structural and Functional Changes in Acromegaly Patients].

Objectives: To investigate the association of growth hormone (GH) and insulin-like growth factor (IGF-1) burden with the cardiac structural and functional changes in acromegaly patients.

Methods: Ninety-nine acromegaly patients were enrolled in this study. According to the normal range of echocardiographic parameters of Peking Union Medical College Hospital, the patients were divided into parameter normal group and abnormal group.

Effect of icariin on fracture healing in an ovariectomized rat model of osteoporosis.

Osteoporosis is frequently asymptomatic, presenting a significant clinical and economic burden, particularly following an osteoporosis-associated fracture. Icariin has been reported to inhibit osteoporosis , and the present study investigated whether icariin also promoted bone fracture healing in ovariectomized osteoporotic (OVX) rats . A total of 30 female rats were randomly divided into three groups (n=10 per group): i) Sham surgery; ii) OVX; and iii) OVX with icariin (OVX + ICA) groups.

Differential Regulation of c-di-GMP Metabolic Enzymes by Environmental Signals Modulates Biofilm Formation in Yersinia pestis.

Cyclic diguanylate (c-di-GMP) is essential for Yersinia pestis biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs), HmsT and HmsD and one phosphodiesterase (PDE), HmsP are responsible for the synthesis and degradation of c-di-GMP in Y. pestis.