Boron enabled bioconjugation chemistries.

Novel bioconjugation reactions have been heavily pursued for the past two decades. A myriad of conjugation reactions have been developed for labeling molecules of interest in their native context as well as for constructing multifunctional molecular entities or stimuli-responsive materials. A growing cluster of bioconjugation reactions were realized by tapping into the unique properties of boron.

Covalent Inhibition of a Host-Pathogen Protein-Protein Interaction Reduces the Infectivity of .

The ever-expanding antibiotic resistance urgently calls for novel antibacterial therapeutics, especially those with a new mode of action. We report herein our exploration of protein-protein interaction (PPI) inhibition as a new mechanism to thwart bacterial pathogenesis. Specifically, we describe potent and specific inhibitors of the pneumococcal surface protein PspC, an important virulence factor that facilitates the infection of Specifically, PspC has been documented to recruit human complement factor H (hFH) to suppress host complement activation and/or promote the bacterial attachment to host tissues.

PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis.

Erythropoiesis and megakaryopoiesis are stringently regulated by signaling pathways. However, the precise molecular mechanisms through which signaling pathways regulate key transcription factors controlling erythropoiesis and megakaryopoiesis remain partially understood. Herein, we identified heat shock cognate B (HSCB), which is well known for its iron-sulfur cluster delivery function, as an indispensable protein for friend of GATA 1 (FOG1) nuclear translocation during erythropoiesis of K562 human erythroleukemia cells and cord-blood-derived human CD34+CD90+hematopoietic stem cells (HSCs), as well as during megakaryopoiesis of the CD34+CD90+HSCs.

Strategies for the Construction of Multicyclic Phage Display Libraries.

Peptide therapeutics have gained great interest due to their multiple advantages over small molecule and antibody-based drugs. Peptide drugs are easier to synthesize, have the potential for oral bioavailability, and are large enough to target protein-protein interactions that are undruggable by small molecules. However, two major limitations have made it difficult to develop novel peptide therapeutics not derived from natural products, including the metabolic instability of peptides and the difficulty of reaching antibody-like potencies and specificities.

The Optimized Design of Soil-Touching Parts of a Greenhouse Humanoid Weeding Shovel Based on Strain Sensing and DEM-ADAMS Coupling Simulation.

To overcome the shortcomings of plowing and rotary tillage, a human-like weeding shoveling machine was designed. The machine's various moving rods were analyzed using Matlab R2019b(9.7.

Chlamydia psittaci causing severe pneumonia with an initial complaint of massive watery sputum: a case report.

Background: With the widespread application of metagenomic next-generation sequencing (mNGS) in pathogen detection, the reports of severe Chlamydia psittaci () pneumonia are increasing. It is essential to determine the best management of severe pneumonia.

Case Description: This report describes a 51-year-old male patient who presented with symptoms of expectoration, relative bradycardia, and dyspnea.

Rapid Grapevine Health Diagnosis Based on Digital Imaging and Deep Learning.

Deep learning plays a vital role in precise grapevine disease detection, yet practical applications for farmer assistance are scarce despite promising results. The objective of this research is to develop an intelligent approach, supported by user-friendly, open-source software named AI GrapeCare (Version 1, created by Osama Elsherbiny). This approach utilizes RGB imagery and hybrid deep networks for the detection and prevention of grapevine diseases.

Functional study of a lytic polysaccharide monooxygenase MsLPMO3 from Morchella sextelata in the oxidative degradation of cellulose.

Lytic polysaccharide monooxygenases (LPMOs) can improve the effectiveness with which agricultural waste is utilized. This study described the potent AA9 family protein MsLPMO3, derived from Morchella sextelata. It exhibited strong binding to phosphoric acid swollen cellulose (PASC), and had the considerable binding ability to Cu with a K value of 2.

Nanoarchitectonics on residual carbon from gasification fine slag upon two step low temperature activation for application in supercapacitors.

In this paper, the carbon electrode materials were prepared by the KOH-HNO low-temperature activation technique using cheap residual carbon from gasification fine slag (CK) as raw materials. The results showed that the prepared material (CKN-2) which obtained by dry-wet sequential activation at 500°C for 1.5 h at carbon to KOH ratio of 1:2 and further at 80°C for 1 h in 2 mol/L HNO solution.

Construction of Nonnatural Cysteine-Cross-Linked Phage Libraries.

Phage display is a powerful technique for rapid construction and screening of peptide libraries with over 10 sequence diversity. The M13 bacteriophage genome can be edited to incorporate randomized amino acids, which will be displayed on its minor coat protein (pIII). To enable screening of nonnatural cyclic peptides on phage, the minor coat protein can be modified with a chemical cross-linker.

Phage Display of Two Distinct Warheads to Inhibit Challenging Proteins.

Falling in between traditional small molecules and antibodies in size, peptides are emerging as a privileged therapeutic modality, one that can harness the benefits of both small molecule and antibody drugs. To discover potential peptide therapeutics, it is highly desirable to have high throughput screening platforms that can assess peptides with diverse and non-natural functional motifs. With this contribution, we present a novel phage library that incorporates two distinct designer groups.

Optimized Design of Touching Parts of Soil Disinfection Machine Based on Strain Sensing and Discrete Element Simulation.

With the increasing level in the intensification of agricultural production in China, continuous cropping obstacles have become a problem that needs to be solved. The use of vertical rotary tillage technology and soil disinfection technology is an effective solution. In this paper, a vertical rotary soil-tilling variable disinfection combine was developed and an on-board control system with STM32 as the control core was designed to realize the real-time acquisition of powder monopoly torque information and the variable application of soil disinfection chemicals.

Diazaborine-Mediated Bicyclization of Native Peptides with Inducible Reversibility.

Multicyclic peptides are appealing candidates for peptide-based drug discovery. While various methods are developed for peptide cyclization, few allow multicyclization of native peptides. Herein we report a novel cross-linker DCA-RMR1, which elicits facile bicyclization of native peptides via N-terminus Cys-Cys cross-linking.

A Cysteine-Directed Proximity-Driven Crosslinking Method for Native Peptide Bicyclization.

Efficient and site-specific modification of native peptides and proteins is desirable for synthesizing antibody-drug conjugates as well as for constructing chemically modified peptide libraries using genetically encoded platforms such as phage display. In particular, there is much interest in efficient multicyclization of native peptides due to the appeals of multicyclic peptides as therapeutics. However, conventional approaches for multicyclic peptide synthesis require orthogonal protecting groups or non-proteinogenic clickable handles.

Study on the Discoloration Mechanism of Eucalyptus Wood during Thermal Treatment in Different Media.

Chromophore structures in wood are the core elements for regulating wood color. Thermal treatment can regulate the color of wood, thus increasing its added value. In this study, conventional thermal treatment was used to regulate the color of Eucalyptus, in order to make its color close to the precious wood species Burma padauk.

Research on NO generation characteristics of ammonia-premixed flame.

Ammonia is a promising fuel with high energy density, accessible storage, and no CO production by combustion, but its combustion produces the pollutant NO. In this study, a Bunsen burner experimental bench was selected to investigate the concentration of NO generated by ammonia combustion at different initial oxygen concentrations. Further, the reaction pathways of NO were analyzed in depth, and sensitivity analysis was performed.

Lysine-Targeted Reversible Covalent Ligand Discovery for Proteins via Phage Display.

Binding via reversible covalent bond formation presents a novel and powerful mechanism to enhance the potency of synthetic inhibitors for therapeutically important proteins. Work on this front has yielded the anticancer drug bortezomib as well as the antisickling drug voxelotor. However, the rational design of reversible covalent inhibitors remains difficult even when noncovalent inhibitors are available as a scaffold.

Fast Cysteine Bioconjugation Chemistry.

Cysteine bioconjugation serves as a powerful tool in biological research and has been widely used for chemical modification of proteins, constructing antibody-drug conjugates, and enabling cell imaging studies. Cysteine conjugation reactions with fast kinetics and exquisite selectivity have been under heavy pursuit as they would allow clean protein modification with just stoichiometric amounts of reagents, which minimizes side reactions, simplifies purification and broadens functional group tolerance. In this concept, we summarize the recent advances in fast cysteine bioconjugation, and discuss the mechanism and chemical principles that underlie the high efficiencies of the newly developed cysteine reactive reagents.

N-Terminal cysteine mediated backbone-side chain cyclization for chemically enhanced phage display.

Phage display, an ingenious invention for evaluating peptide libraries, has been limited to natural peptides that are ribosomally assembled with proteinogenic amino acids. Recently, there has been growing interest in chemically modifying phage libraries to create nonnatural cyclic and multicyclic peptides, which are appealing for use as inhibitors of protein-protein interactions. While earlier reports largely focused on side-chain side-chain cyclization, we report herein a novel strategy for creating backbone-side chain cyclized peptide libraries on phage.

A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance.

Detailed knowledge on how bacteria evade antibiotics and eventually develop resistance could open avenues for novel therapeutics and diagnostics. It is thereby key to develop a comprehensive genome-wide understanding of how bacteria process antibiotic stress, and how modulation of the involved processes affects their ability to overcome said stress. Here we undertake a comprehensive genetic analysis of how the human pathogen Streptococcus pneumoniae responds to 20 antibiotics.

How Different Is the Annual Physical Examination of Older Migrants than That of Older Nonmigrants? A Coarsened Exact Matching Study from China.

It has become a top priority to ensure equal rights for older migrants in China. This study aims to explore how different the annual physical examination of older migrants is compared to that of older nonmigrants in China by using a coarsened exact matching method, and to explore the factors affecting annual physical examination among older migrants in China. Data were drawn from the China Migrants Dynamic Survey 2015 and China Health and Retirement Longitudinal Survey 2015.

Is Travel Time Associated with Health Service Utilization in Northwest China? Evidence from Shaanxi Province.

Purpose: Northwest China has a large area, low population density, and few health resources, which makes the utilization of health resources in this region difficult. The objective of this study was to assess utilization of health services and its association with travel time in Shaanxi Province.

Patients And Methods: Data were obtained from the fifth Household Health Service Survey of Shaanxi Province conducted in 2013.