FL058, a novel β-lactamase inhibitor, increases the anti-Mycobacterium abscessus activity of imipenem.

Background: β-lactams are crucial for anti-Mycobacterium abscessus complex (MABC) therapy. Treating infections is challenging since MABC produces a class A β-lactamase (Bla , which is capable of hydrolyzing β-lactams thus causing drug resistance. Diazabicyclooctane (DBO) β-lactamase inhibitors (BLIs) can inhibit Bla.

The NCR1 transporter is an antimalarial target that exports cholesterol from the parasite's plasma membrane.

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria, , has developed resistance to nearly all currently available antimalarial drugs. The Niemann-Pick type C1-related (PfNCR1) transporter has been identified as a druggable target, but its structure and detailed molecular mechanism are not yet available.

Elucidating the dynamics of Integrin αIIb[beta]3 from native platelet membranes by cryo-EM with build and retrieve method.

Platelets fulfill their essential physiological roles sensing the extracellular environment through their membrane proteins. The native membrane environment provides essential regulatory cues that impact the protein structure and mechanism of action. Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures of membrane proteins to be solved from homogeneous samples.

Cryo-EM structure of the MmpL5-AcpM complex.

Unlabelled: , the causative agent of the airborne infection tuberculosis (TB), contains 13 mycobacterial membrane protein large (MmpL) transporters that can be divided into two distinct subclasses. These MmpL proteins play important functional roles within the mycobacterium and subsequently are considered attractive drug targets to combat TB infection. Previously, we reported both X-ray and cryo-electron microscopy (cryo-EM) structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins.

TBAJ-587, a novel diarylquinoline, is active against .

Nontuberculous mycobacteria (NTM) infections are extremely difficult to treat due to a natural resistance to many antimicrobials. TBAJ-587 is a novel diarylquinoline, which shows higher anti-tuberculosis activity, lower lipophilicity, and weaker inhibition of hERG channels than bedaquiline (BDQ). The susceptibilities of 11 NTM reference strains and 194 clinical isolates to TBAJ-587 were determined by the broth microdilution assay.

Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.

The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins.

A biofilm-tropic bacteriophage uses the exopolysaccharide Psl as receptor.

Bacteria in nature can exist in multicellular communities called biofilms. Biofilms also form in the course of many infections. infections frequently involve biofilms, which contribute materially to the difficulty to treat these infections with antibiotic therapy.

Cryo-EM structures of the human band 3 transporter indicate a transport mechanism involving the coupled movement of chloride and bicarbonate ions.

The band 3 transporter is a critical integral membrane protein of the red blood cell (RBC), as it is responsible for catalyzing the exchange of bicarbonate and chloride anions across the plasma membrane. To elucidate the structural mechanism of the band 3 transporter, detergent solubilized human ghost membrane reconstituted in nanodiscs was applied to a cryo-EM holey carbon grid to define its composition. With this approach, we identified and determined structural information of the human band 3 transporter.

An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria.

Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F.

Structural basis of DNA recognition of the CosR regulator.

Unlabelled: is a foodborne pathogen commonly found in the intestinal tracts of animals. This pathogen is a leading cause of gastroenteritis in humans. Besides its highly infectious nature, is increasingly resistant to a number of clinically administrated antibiotics.

The predictive value of modified-DeepSurv in overall survivals of patients with lung cancer.

The traditional prognostic model may induce the possibility of incorrect assessment of mortality risk under the assumption of linearity. It is urgent to develop a non-linearity precise prognostic model for achieving personalized medicine in lung cancer. In our study, we develop and validate a prognostic model "Modified-DeepSurv" for patients with lung carcinoma based on deep learning and evaluate its value for prognosis, while Cox proportional hazard regression was used to develop another model "CPH.

Single-Cell Profiling of Tumor-Associated Neutrophils in Advanced Non-Small Cell Lung Cancer.

Purpose: Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.

Materials And Methods: We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens.

GlnR activated transcription of nitrogen metabolic pathway genes facilitates biofilm formation by mycobacterium abscessus.

Objectives: Nitrogen is indispensable for the synthesis of biomacromolecules. The correlation between nitrogen metabolism and Mycobacterium abscessus (M. abscessus) biofilm formation is unclear.

High-Resolution Structural Proteomics of Mitochondria Using the 'Build and Retrieve' Methodology.

The application of integrated systems biology to the field of structural biology is a promising new direction, although it is still in the infant stages of development. Here we report the use of single particle cryo-EM to identify multiple proteins from three enriched heterogeneous fractions prepared from human liver mitochondrial lysate. We simultaneously identify and solve high-resolution structures of nine essential mitochondrial enzymes with key metabolic functions, including fatty acid catabolism, reactive oxidative species clearance, and amino acid metabolism.

The Safety and Efficacy of Prolonged Use of Bedaquiline for the Treatment of Patients with Pulmonary Multi-Drug Resistant/Rifampin-Resistant Tuberculosis: A Prospective, Cohort Study in China.

Objective: To evaluate the safety, tolerability, and efficacy of prolonged bedaquiline (Bdq) treatment in patients with multi-drug/rifampin-resistant tuberculosis (MDR/RR-TB).

Methods: This prospective cohort study was performed from August 2018 to August 2021. Patients diagnosed with MDR/RR-TB who met the inclusion criteria were prospectively included.

Comparative study of K-wire combined with screw vs. K-wire in the treatment of AO type B3.1 phalangeal fractures.

Purpose: The purpose of this study was to introduce the surgical method of K-wire combined with screw in the treatment of Arbeitsgemeinschaftfür Osteosynthesefragen (AO) type B3.1 phalangeal fractures and to compare its clinical, radiological and functional outcomes with K-wire fixation.

Methods: This was a retrospective comparative study.

Results after open lunate excision alone or in combination with palmaris longus tendon ball arthroplasty for the treatment of Kienböck's disease.

Purpose: This study aims to compare results after open lunate excision alone and in combination with palmaris longus tendon ball arthroplasty for the treatment of late-staged Kienböck's disease (KD).

Methods: This is a retrospective study using the prospectively collected data, and patients who had a discharge diagnosis of KD (stage IIIB based on Lichtman staging criteria) and underwent surgical treatment by lunate excision alone or in combination with palmaris longus tendon ball arthroplasty between January 2011 and December 2020 were included in this study. Variables of interest involved demographics, disease condition, operative procedure, and the outcomes evaluated at the last follow-up.

Identify the Clinicopathological Characteristics of Lung Carcinoma Patients Being False Negative in Folate Receptor Based Circulating Tumor Cell Detection.

In lung cancer diagnosis, folate receptor (FR)-based circulating tumor cell (CTC) has shown its ability to distinguish malignancy from benign disease to some extent. However, there are still some patients that cannot be identified by FR-based CTC detection. And studies comparing the characteristics between true positive (TP) and false negative (FN) patients are few.

Impaired ESX-3 Induces Bedaquiline Persistence in Mycobacterium abscessus Growing Under Iron-Limited Conditions.

ESX-3 is a secretion pathway which is essential for mycobactin-mediated iron acquisition under iron-limited conditions. Although present in all Mycobacterium sp., ESX-3 remains to be elucidated in Mycobacterium abscessus.

High-resolution structural-omics of human liver enzymes.

We applied raw human liver microsome lysate to a holey carbon grid and used cryo-electron microscopy (cryo-EM) to define its composition. From this sample we identified and simultaneously determined high-resolution structural information for ten unique human liver enzymes involved in diverse cellular processes. Notably, we determined the structure of the endoplasmic bifunctional protein H6PD, where the N- and C-terminal domains independently possess glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase enzymatic activity, respectively.

Cryo-Electron Microscopy Structures of a Campylobacter Multidrug Efflux Pump Reveal a Novel Mechanism of Drug Recognition and Resistance.

Campylobacter jejuni is a bacterium that is commonly present in the intestinal tracts of animals. It is also a major foodborne pathogen that causes gastroenteritis in humans. The most predominant and clinically important multidrug efflux system in C.

Omadacycline, Eravacycline, and Tigecycline Express Anti-Mycobacterium abscessus Activity .

Mycobacterium abscessus infections are increasing worldwide necessitating the development of new antibiotics and treatment regimens. The utility of third-generation tetracycline antibiotics was reestablished; their anti-M. abscessus activity needs further study.

Cryo-EM Structures of the Klebsiella pneumoniae AcrB Multidrug Efflux Pump.

The continued challenges of the COVID-19 pandemic combined with the growing problem of antimicrobial-resistant bacterial infections has severely impacted global health. Specifically, the Gram-negative pathogen Klebsiella pneumoniae is one of the most prevalent causes of secondary bacterial infection in COVID-19 patients, with approximately an 83% mortality rate observed among COVID-19 patients with these bacterial coinfections. K.

Correlation Analysis and Prediction Model of Thermal Protection Performance of Aramid 1414 Fabric.

The thermal protection performance of fire suit is vital to the safety of firefighters. Using certain physical properties of fabrics to evaluate their thermal protection performance speeds up the process. This work aims to develop a TPP value prediction model that can be easily applied.

Differential organ-specific tumor response to first-line immune checkpoint inhibitor therapy in non-small cell lung cancer-a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) possess remarkable clinical effectiveness in non-small cell lung cancer (NSCLC). Different immune profiles of tumors may play a key role in the efficacy of treatment with ICIs. This article aimed to determine the differential organ responses to ICI in individuals with metastatic NSCLC.