Computed tomography-based radial endobronchial ultrasound image simulation of peripheral pulmonary lesions using deep learning.

Background And Objectives: Radial endobronchial ultrasound (R-EBUS) plays an important role during transbronchial sampling of peripheral pulmonary lesions (PPLs). However, existing navigational bronchoscopy systems provide no guidance for R-EBUS. To guide intraoperative R-EBUS probe manipulation, we aimed to simulate R-EBUS images of PPLs from preoperative computed tomography (CT) data using deep learning.

Combining an Enhanced Polyphosphate Kinase-Driven UDP-Glucose Regeneration System with the Screening of Key Glycosyltransferases for Efficient Synthesis of Nucleoside Disaccharides.

Nucleoside disaccharides are essential glycosides that naturally occur in specific living organisms. This study developed an enhanced UDP-glucose regeneration system to facilitate the multienzyme synthesis of nucleoside disaccharides by integrating it with nucleoside-specific glycosyltransferases. The system utilizes maltodextrin and polyphosphate as cost-effective substrates for UDP-glucose supply, catalyzed by α-glucan phosphorylase (αGP) and UDP-glucose pyrophosphorylase (UGP).

Engineering a Robust UDP-Glucose Pyrophosphorylase for Enhanced Biocatalytic Synthesis via ProteinMPNN and Ancestral Sequence Reconstruction.

UDP-glucose is a key metabolite in carbohydrate metabolism and plays a vital role in glycosyl transfer reactions. Its significance spans across the food and agricultural industries. This study focuses on UDP-glucose synthesis via multienzyme catalysis using dextrin, incorporating UTP production and ATP regeneration modules to reduce costs.

Development of non-β-Lactam covalent allosteric inhibitors targeting PBP2a in Methicillin-Resistant .

Methicillin-resistant (MRSA), a Gram-positive bacterial pathogen, continues to pose a serious threat to the current public health system in our society. The high level of resistance to β-lactam antibiotics in MRSA is attributed to the expression of penicillin-binding protein 2a (PBP2a), which catalyzes cell wall cross-linking. According to numerous research reports, the activity of the PBP2a protein is known to be regulated by an allosteric site distinct from the active site where cell wall cross-linking occurs.

Engineering the thermal stability of a polyphosphate kinase by ancestral sequence reconstruction to expand the temperature boundary for an industrially applicable ATP regeneration system.

ATP-dependent energy-consuming enzymatic reactions are widely used in cell-free biocatalysis. However, the direct addition of large amounts of expensive ATP can greatly increase cost, and enzymatic production is often difficult to achieve as a result. Although a polyphosphate kinase (PPK)-polyphosphate-based ATP regeneration system has the potential to solve this challenge, the generally poor thermal stability of PPKs limits the widespread use of this method.

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with > 50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure.

Cryo-EM structure of amyloid fibril formed by α-synuclein hereditary A53E mutation reveals a distinct protofilament interface.

Synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple systems atrophy (MSA), have the same pathologic feature of misfolded α-synuclein protein (α-syn) accumulation in the brain. PD patients who carry α-syn hereditary mutations tend to have earlier onset and more severe clinical symptoms than sporadic PD patients. Therefore, revealing the effect of hereditary mutations to the α-syn fibril structure can help us understand these synucleinopathies' structural basis.

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii.

Carbapenem-resistant (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with > 50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure.

Broadband Achromatic Metalens in the Visible Light Spectrum Based on Fresnel Zone Spatial Multiplexing.

Metalenses composed of a large number of subwavelength nanostructures provide the possibility for the miniaturization and integration of the optical system. Broadband polarization-insensitive achromatic metalenses in the visible light spectrum have attracted researchers because of their wide applications in optical integrated imaging. This paper proposes a polarization-insensitive achromatic metalens operating over a continuous bandwidth from 470 nm to 700 nm.

A Cascaded Multi-Task Generative Framework for Detecting Aortic Dissection on 3-D Non-Contrast-Enhanced Computed Tomography.

Contrast-enhanced computed tomography (CE-CT) is the gold standard for diagnosing aortic dissection (AD). However, contrast agents can cause allergic reactions or renal failure in some patients. Moreover, AD diagnosis by radiologists using non-contrast-enhanced CT (NCE-CT) images has poor sensitivity.

Knee Bone and Cartilage Segmentation Based on a 3D Deep Neural Network Using Adversarial Loss for Prior Shape Constraint.

Fast and accurate segmentation of knee bone and cartilage on MRI images is becoming increasingly important in the orthopaedic area, as the segmentation is an essential prerequisite step to a patient-specific diagnosis, optimising implant design and preoperative and intraoperative planning. However, manual segmentation is time-intensive and subjected to inter- and intra-observer variations. Hence, in this study, a three-dimensional (3D) deep neural network using adversarial loss was proposed to automatically segment the knee bone in a resampled image volume in order to enlarge the contextual information and incorporate prior shape constraints.

CT-based radiomics signature analysis for evaluation of response to induction chemotherapy and progression-free survival in locally advanced hypopharyngeal carcinoma.

Objectives: To establish and validate a CT radiomics model for prediction of induction chemotherapy (IC) response and progression-free survival (PFS) among patients with locally advanced hypopharyngeal carcinoma (LAHC).

Methods: One hundred twelve patients with LAHC (78 in training cohort and 34 in validation cohort) who underwent contrast-enhanced CT (CECT) scans prior to IC were enrolled. Least absolute shrinkage and selection operator (LASSO) was used to select the crucial radiomic features in the training cohort.

Computed tomography-based radiomics signature as a pretreatment predictor of progression-free survival in locally advanced hypopharyngeal carcinoma with a different response to induction chemotherapy.

Purpose: To establish and validate a radiomics signature for stratifying the risk of progression-free survival (PFS) in patients with locally advanced hypopharyngeal carcinoma (LAHC) undergoing induction chemotherapy (IC).

Methods: We extracted radiomics features from baseline contrast-enhanced computed tomography (CECT) images. We enrolled 112 LAHC patients (78 in the training cohort and 34 in the validation cohort).

A cocktail of protein engineering strategies: Breaking the enzyme bottleneck one by one for high UTP production in vitro.

The pyrimidine metabolic pathway is tightly regulated in microorganisms, allowing limited success in metabolic engineering for the production of pathway-related substances. Here, we constructed a four-enzyme coupled system for the in vitro production of uridine triphosphate (UTP). The enzymes used include nucleoside kinase, uridylate kinase, nucleoside diphosphate kinase, and polyphosphate kinase for energy regeneration.

Deep Learning for Accurate Segmentation of Venous Thrombus from Black-Blood Magnetic Resonance Images: A Multicenter Study.

Objective: Deep vein thrombosis (DVT) is the third-largest cardiovascular disease, and accurate segmentation of venous thrombus from the black-blood magnetic resonance (MR) images can provide additional information for personalized DVT treatment planning. Therefore, a deep learning network is proposed to automatically segment venous thrombus with high accuracy and reliability.

Methods: In order to train, test, and external test the developed network, total images of 110 subjects are obtained from three different centers with two different black-blood MR techniques (i.

A Cascaded Deep Learning Framework for Detecting Aortic Dissection Using Non-contrast Enhanced Computed Tomography.

Aortic dissection (AD) is a rare but potentially fatal disease with high mortality. The aim of this study is to synthesize contrast enhanced computed tomography (CE-CT) images from non-contrast CT (NCE-CT) images for detecting aortic dissection. In this paper, a cascaded deep learning framework containing a 3D segmentation network and a synthetic network was proposed and evaluated.

In vitro biosynthesis of ATP from adenosine and polyphosphate.

Adenosine triphosphate (ATP) acts as a crucial energy currency in vivo, and it is a widely used energy and/or phosphate donor for enzyme-catalyzed reactions in vitro. In this study, we established an in vitro multi-enzyme cascade system for ATP production. Using adenosine and inorganic polyphosphate (polyP) as key substrates, we combined adenosine kinase and two functionally distinct polyphosphate kinases (PPKs) in a one-pot reaction to achieve chain-like ATP regeneration and production.

The α-synuclein hereditary mutation E46K unlocks a more stable, pathogenic fibril structure.

Aggregation of α-synuclein is a defining molecular feature of Parkinson's disease, Lewy body dementia, and multiple systems atrophy. Hereditary mutations in α-synuclein are linked to both Parkinson's disease and Lewy body dementia; in particular, patients bearing the E46K disease mutation manifest a clinical picture of parkinsonism and Lewy body dementia, and E46K creates more pathogenic fibrils in vitro. Understanding the effect of these hereditary mutations on α-synuclein fibril structure is fundamental to α-synuclein biology.

Different Amyloid-β Self-Assemblies Have Distinct Effects on Intracellular Tau Aggregation.

Alzheimer's disease (AD) pathology is characterized by the aggregation of beta-amyloid (Aβ) and tau in the form of amyloid plaques and neurofibrillary tangles in the brain. It has been found that a synergistic relationship between these two proteins may contribute to their roles in disease progression. However, how Aβ and tau interact has not been fully characterized.

Structures of fibrils formed by α-synuclein hereditary disease mutant H50Q reveal new polymorphs.

Deposits of amyloid fibrils of α-synuclein are the histological hallmarks of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, with hereditary mutations in α-synuclein linked to the first two of these conditions. Seeing the changes to the structures of amyloid fibrils bearing these mutations may help to understand these diseases. To this end, we determined the cryo-EM structures of α-synuclein fibrils containing the H50Q hereditary mutation.

Conformational Dynamics, Intramolecular Domain Conformation Signaling, and Activation of Apo-FimD Revealed by Single-Molecule Fluorescence Resonance Energy Transfer Studies.

The chaperone-usher secretion pathway is a conserved bacterial protein secretion system dedicated to the biogenesis of adhesive fibers. Usher, a multidomain-containing outer membrane protein, plays a central role in this process by acting as a molecular machine that recruits different chaperone-subunit complexes, catalyzes subunit polymerization, and forms a channel for secretion of the assembled subunits. While recent crystal structural studies have greatly advanced our understanding of the structure and function of ushers, the overall architecture of the full-length apo-usher, the molecular events that dictate conformational changes in usher during pilus biogenesis, and its activation by the specific chaperone-adhesin complex remain largely elusive.

Astrocytes Protect Neurons in the Hippocampal CA3 Against Ischemia by Suppressing the Intracellular Ca Overload.

In the hippocampus, delayed neuronal death is normally seen in neurons of the CA1 region but not in those of the CA3 region. Astrocytes have been reported to play multiple supporting or pathological roles in neuronal functioning. While evidence indicates that astrocytes could exert neuroprotective effects following ischemia, the possible underlying mechanisms remain unclear.

BCCIPβ modulates the ribosomal and extraribosomal function of S7 through a direct interaction.

Extraribosomal functions of ribosomal proteins (RPs) have gained much attention for their implications in tumorigenesis and progression. However, the regulations for transition between the ribosomal and extraribosomal functions of RPs are rarely reported. Herein, we identified a ribosomal protein S7-interacting partner, BCCIPβ, which modulates the functional conversion of S7.