Advancing In-Depth N-Terminomics Detection with a Cleavable 2-Pyridinecarboxyaldehyde Probe.

Proteolysis, an irreversible post-translational modification catalyzed by proteases, plays a crucial role in various biological processes. Exploring abnormally hydrolyzed proteins in pathological tissues is a valuable approach for elucidating the mechanisms underlying disease development. Herein, we have developed a cleavable 2-pyridinecarboxyaldehyde probe (2PCA-Probe) that enables efficient and in-depth N-terminomics detection, addressing limitations of previous methods. Furthermore, we unexpectedly discovered a new marker capable of identifying N-terminal chemical labeling with the 2PCA-Probe and elucidated the reaction mechanism. Using this probe, we identified 4686 N-terminal peptides in colorectal cancer and adjacent tissues, significantly expanding the depth of the N-terminome and revealing the potential role of abnormal protein hydrolysis in colorectal cancer development.

Controlled Reversible N-Terminal Modification of Peptides and Proteins.

A reversible modification strategy enables a switchable cage/decage process of proteins with an array of applications for protein function research. However, general N-terminal selective reversible modification strategies which present site selectivity are specifically limited. Herein, we report a general reversible modification strategy compatible with 20 canonical amino acids at the N-terminal site by the palladium-catalyzed cinnamylation of native peptides and proteins under biologically relevant conditions. This approach broadens the substrate adaptability of N-terminal modification of proteins and shows a potential impact on the more challenging protein substrates such as antibodies. In the presence of 1,3-dimethylbarbituric acid, palladium-catalyzed deconjugation released native peptides and proteins efficiently. Harnessing the reversible nature of this protocol, practical applications were demonstrated by precise function modulation of antibodies and traceless enrichment of the protein-of-interest for proteomics analysis. This novel on/off strategy working on the N-terminus will provide new opportunities in chemical biology and medicinal research.

Structural design of an improved SPIDER optical system based on a multimode interference coupler.

The Segmented Planar Imaging Detector for Electro-Optical Reconnaissance (SPIDER) is a small volume, lightweight, low energy consumption, and high-resolution system expected to replace traditional large aperture telescopes for long-distance detection. In this paper, an improved SPIDER system is proposed, which uses a multimode interference (MMI) coupler instead of an orthogonal detector, and successfully doubles the space spectrum coverage. We present a three-point configuring method to configure lenslets, calculate spatial spectrum values from the output currents obtained by MMI. By comparing the performance of the MMI-SPIDER and SPIDER systems through simulations, we demonstrate that the former has more complete spatial spectrum coverage, resulting in better image restoration quality.

Efficient and accurate registration with BWPH descriptor for low-quality point clouds.

Point cloud registration based on local descriptors plays a crucial role in 3D computer vision applications. However, existing methods often suffer from limitations such as low accuracy, a large memory footprint, and slow speed, particularly when dealing with 3D point clouds from low-cost sensors. To overcome these challenges, we propose an efficient local descriptor called Binary Weighted Projection-point Height (BWPH) for point cloud registration. The core idea behind the BWPH descriptor is the integration of Gaussian kernel density estimation with weighted height characteristics and binarization components to encode distinctive information for the local surface. Through extensive experiments and rigorous comparisons with state-of-the-art methods, we demonstrate that the BWPH descriptor achieves high matching accuracy, strong compactness, and feasibility across contexts. Moreover, the proposed BWPH-based point cloud registration successfully registers real datasets acquired by low-cost sensors with small errors, enabling accurate initial alignment positions.

MInet: A Novel Network Model for Point Cloud Processing by Integrating Multi-Modal Information.

Three-dimensional LiDAR systems that capture point cloud data enable the simultaneous acquisition of spatial geometry and multi-wavelength intensity information, thereby paving the way for three-dimensional point cloud recognition and processing. However, due to the irregular distribution, low resolution of point clouds, and limited spatial recognition accuracy in complex environments, inherent errors occur in classifying and segmenting the acquired target information. Conversely, two-dimensional visible light images provide real-color information, enabling the distinction of object contours and fine details, thus yielding clear, high-resolution images when desired. The integration of two-dimensional information with point clouds offers complementary advantages. In this paper, we present the incorporation of two-dimensional information to form a multi-modal representation. From this, we extract local features to establish three-dimensional geometric relationships and two-dimensional color relationships. We introduce a novel network model, termed MInet (Multi-Information net), which effectively captures features relating to both two-dimensional color and three-dimensional pose information. This enhanced network model improves feature saliency, thereby facilitating superior segmentation and recognition tasks. We evaluate our MInet architecture using the ShapeNet and ThreeDMatch datasets for point cloud segmentation, and the Stanford dataset for object recognition. The robust results, coupled with quantitative and qualitative experiments, demonstrate the superior performance of our proposed method in point cloud segmentation and object recognition tasks.

Specific interaction of insulin receptor and GLP-1 receptor mediates crosstalk between their signaling.

Both GLP-1 receptor (GLP-1R) and insulin receptor (IR) transmit signals for insulin release and/or cellular metabolism although using distinct sets of transducing molecules and separate pathways. We proposed a possible association of IR and GLP-1R, since they are coexpressed in diverse tissues including the pancreatic ß-cells and crosstalk between their signaling was frequently reported. We showed a specific interaction between GLP-1R and IR which was independent of intracellular receptor domains and not responsive to ligand binding. In signaling, the IRS-1 was coupled more to GLP-1R and less to IR in the receptor complex at IR activation, with subsequent IRS-1 degradation suppressed rather than its activation inhibited. The Gsα recruitment to the activated GLP-1R was inhibited in the GLP-1R/IR complex, with the signaling in cAMP pathway suppressed at IR activation. Therefore, the identified GLP-1R/IR complex recruits their signaling molecules which are differentially modified, leading to a crosstalk between their signaling.

Dimerization/oligomerization of the extracellular domain of the GLP-1 receptor and the negative cooperativity in its ligand binding revealed by the improved NanoBiT.

The glucagon-like peptide-1 receptor (GLP-1R), a family B G-protein coupled receptor (GPCR), regulates the insulin secretion following stimulation by ligands. The transmembrane domain (TM) mediates GLP-1R homodimerization, which modulates its ligand binding and signaling. We investigated the possible involvement of the N-terminal extracellular domain (NTD) in dimerization/oligomerization and dimer-associated ligand binding by NanoLuc Binary Technology (NanoBiT). With improved NanoBiT detection using a decreasing substrate concentration, the negative cooperativity of ligand binding to the NTD was confirmed by accelerated dissociation and Scatchard analysis. The dimerization/oligomerization of the isolated NTD was observed by NanoBiT and validated by analytical ultracentrifugation, deriving the comparable dimerization affinity (~105  M-1 ). The NTD was also involved in the dimerization/oligomerization of the full-length GLP-1R with mutated TM4 at the cellular level. In an analysis of the parameters of the NTD binding, the Kd for the probe GLP-1 (7-36, A8G) was similar (6-8 µM) in both the 1:1 binding model and the receptor dimerization model. Compared with GLP-1 and dulaglutide, exenatide showed two-site binding with Ki values of 1.4 pM and 8.7 nM. Our study indicates the involvement of NTD in the GLP-1R dimerization/oligomerization and suggests that further investigations on the role in other family B GPCRs are needed.

Mechanism underlying Polygonum capitatum effect on Helicobacter pylori-associated gastritis based on network pharmacology.

Helicobacter pylori (H. pylori) infection is a common disease that can cause H. pylori-associated gastritis (HAG), peptic ulcers, and gastric cancer. As a traditional Chinese medicine, Polygonum capitatum (PC) manifests its unique advantages in the prevention and treatment of complex diseases and chronic diseases, due to its ability to clear heat, detoxify and relieve pain, promote blood circulation, and remove blood stasis. In order to explore the molecular mechanism of PC for HAG, the study collected the predicted targets of active compounds, conducted functional analysis by the STRING database, collected HAG differential expression genes, and conducted KEGG enrichment analysis on the intersection of predicted targets and differential expression genes of gastritis by Cluego. The results show that PC works mainly by affecting phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2 and nuclear transposition of NF-κB p65 and p-p38MAPK, which has been proved by in vivo and in vitro experiments. These results suggest that PC may act on HAG with multiple targets and pathways, and play a key role in the process of HAG treatment.

Strain-tunable CO2 storage by black phosphorene and α-PC from combined first principles and molecular dynamics studies.

2D layered materials are intrinsically promising mediums for gas adsorption because of their recognized large surface areas and structural stability. Their gas adsorption and desorption processes are usually controlled by changing the temperature or applying high voltage. In this work, though combined density functional theory (DFT) calculations and molecular dynamics (MD) simulations, we propose that external tensile strain can also regulate the gas binding energetics and kinetics using two representative 2D materials, monolayer black phosphorene (BP) and black phosphorus carbide (α-PC), as showpiece models. The DFT results clearly show that CO2 can be physically adsorbed on BP/α-PC with moderate binding strength, which facilities the adsorption and desorption processes. For BP, strain increases the storage capacity from 10.90 ± 0.28 mmol g-1 (strain free) to 12.67 ± 0.33 (30% strain) with a tunability of 16.2%. α-PC, however, has a smaller strain response; its CO2 storage capacity increases from 15.98 ± 0.34 mmol g-1 (strain free) to 17.15 ± 0.36 mmol g-1 for a 10% strained state. DFT calculations reveal that CO2 is an electron acceptor for both BP and α-PC; however, it hardly regulates their electronic structures. The theoretical investigations suggest that BP and α-PC have great potential as gas capture and storage materials. The strain controlling approach can be generalized for the design of tunable nano-devices by external mechanical stimuli.

Rhodium(III)-Catalyzed [4+2] Annulation via C-H Activation: Synthesis of Multi-Substituted Naphthalenone Sulfoxonium Ylides.

A convenient Rh(III)-catalyzed C-H activation and cascade [4+2] annulation for the synthesis of naphthalenone sulfoxonium ylides has been developed. This method features perfect regioselectivity, mild and redox-neutral reaction conditions, and broad substrate tolerance with good to excellent yields. Preliminary mechanistic experiments were conducted and a plausible reaction mechanism was proposed. The new type naphthalenone sulfoxonium ylides could be further transformed into multi-substituted naphthols, which demonstrates the practical utility of this methodology.

Recent approaches for asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes.

This review article critically discusses examples of asymmetric synthesis of tailor-made α-amino acids via homologation of Ni(II) complexes of glycine and alanine Schiff bases, reported in the literature from 2013 through the end of 2016. Where it is possible, reaction mechanism and origin of the stereochemical outcome is discussed in detail. Special attention is given to various aspects of practicality and scalability of the reported methods. Among the most noticeable developments in this area are novel designs of axially chiral ligands, application of electro- and mechano-chemical (ball-milling) conditions, and development of dynamic kinetic resolution procedures.

Insulin chains as efficient fusion tags for prokaryotic expression of short peptides.

Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli. All the tested peptides including glucagon-like peptide 1 (GLP-1), a C-terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting. All recombinant products were expressed in inclusion bodies. The effective accumulation of products was largely attributed to the insoluble expression induced by fusion with insulin chains, and was confirmed by the fusion expression of transthyretin. Insulin chains thus show promise as efficient fusion tags for mass production of heterologous peptides in prokaryotes.

Genome-wide identification and analysis of the EIN3/EIL gene family in broomcorn millet (Panicum miliaceum L.).

The EIN3/EIL gene family holds a pivotal role as it encodes a crucial transcription factor in plants. During the process of polyploidization in broomcorn millet (Panicum miliaceum L.), there is an intriguing above-average amplification observed within the EIN3/EIL gene family. Nonetheless, our current knowledge of this gene family in broomcorn millet remains limited. Hence, in this study, we conducted a comprehensive analysis of the EIN3/EIL gene family in broomcorn millet, aiming to provide a deeper understanding of the potential evolutionary changes. Additionally, we analyzed the EIN3/EIL gene family of Panicum hallii L., a close relative of broomcorn millet, to enhance our characterization efforts. Within this study, we identified a total of 15 EIN3/EIL genes specific to broomcorn millet. Through covariance analysis, it was revealed that all PmEIL genes, except PmEIL1 and PmEIL15, had duplicate copies generated through genome-wide duplication events. Importantly, the Ka/Ks values of all duplicated genes were found to be less than 1, indicating strong purifying selection. Phylogenetic analysis showed that these genes could be categorized into four distinct evolutionary branches, showcasing similar characteristics among members within the same branch. However, there appeared to be an uneven distribution of cis-acting elements amid the EIN3/EIL genes. Further examination of transcriptomic data shed light on the diverse spatiotemporal and stress-related expression patterns exhibited by the EIN3/EIL genes in broomcorn millet. Notably, under cold stress, the expression of PmEIL3/4/8/14 was significantly up-regulated, while under drought stress, PmEIL4/5/6 displayed significant up-regulation. Intriguingly, the expression pattern of PmEIL15 showed an opposite pattern in resistant and sensitive cultivars. The findings of this study augment our understanding of the EIN3/EIL gene family in broomcorn millet and offer a valuable reference for future investigations into polyploid studies. Moreover, this study establishes a theoretical foundation for further exploration of the ethylene signaling pathway in broomcorn millet.

Deciphering the Influence of Anionic Electrons of Surface-Functionalized Two-Dimensional Electrides in Lithium-Sulfur Batteries.

Using transition metal compounds as sulfur hosts is regarded as a promising approach to suppress the polysulfide shuttle and accelerate redox kinetics for lithium-sulfur (Li-S) batteries. Herein, we report that a new kind of compound, electrides (exotic ionic crystalline materials in which electrons serve as anions), is efficient sulfur hosts for Li-S batteries for the first time. Based on the first-principles calculations, we found that two-dimensional (2D) electrides M2C (M = Sc, Y) exhibit unprecedentedly strong binding strength toward sulfur species and surface functionalization is necessary to passivate their activity. The 2D electrides modified with the F-functional group exhibit the best performance in terms of the adsorption energy and sulfur reduction process. A comparative study with a nonelectride reveals that the anionic electrons (AEs) of electrides aid in anchoring the soluble polysulfides. These results open an avenue for the application of electrides in Li-S batteries.

Insights into Photoinduced Carrier Dynamics and Overall Water Splitting of Z-Scheme van der Waals Heterostructures with Intrinsic Electric Polarization.

Using first-principles calculations in combination with nonadiabatic molecular dynamics (NAMD), we propose novel heterostructures of carbon nitride (C7N6) and the Janus GaSnPS monolayer as promising direct Z-scheme photocatalysts for solar-driven overall water splitting. The out-of-plane electric field due to the electric polarization which is dependent on the stacking pattern alters the band alignment and catalytic activity of the heterostructures. The relatively strong interfacial nonadiabatic coupling and long quantum coherence time accelerate the interlayer carrier recombination, enabling a direct Z-scheme photocatalytic mechanism. More importantly, the redox ability of the remanent photogenerated carriers in the Z scheme is strong enough to trigger both the hydrogen evolution reaction (HER) and oxygen reduction reaction (OER) simultaneously without the help of sacrificial agents. Our work reveals a fundamental understanding of ultrafast charge carrier dynamics at vdW heterointerfaces as well as new design prospects for highly efficient direct Z-scheme photocatalysts.

[Spatiotemporal Distribution Characteristics of Co-pollution of PM2.5 and Ozone over BTH with Surrounding Area from 2015 to 2021].

PM2.5 and ozone co-pollution, which are harmful to not only human health but also the social economy, has become the pivotal issue in air pollution prevention and synergistic control, especially in Beijing-Tianjin-Hebei and its surrounding areas and "2+26" cities. It is necessary to analyze the correlation between PM2.5 and ozone concentration and explore the mechanism of PM2.5 and ozone co-pollution. In order to study the characteristics of PM2.5 and ozone co-pollution in Beijing-Tianjin-Hebei with its surrounding area, ArcGIS and SPSS software were used to analyze the correlation between air quality data and meteorological data of the "2+26" cities in Beijing-Tianjin-Hebei and its surrounding areas from 2015 to 2021. The results indicated:① PM2.5 pollution constantly decreased from 2015 to 2021, and the pollution was concentrated in the central and southern parts of the region; ozone pollution showed a trend of fluctuation and presented a pattern of "low in the southwest and high in the northeast" spatially. In terms of seasonal variation, PM2.5concentration was mainly in the order of winter>spring ≈ autumn>summer, and O3-8h concentration was in the order of summer>spring>autumn>winter. ② In the research area, days with PM2.5 exceeding the standard continued to decline, whereas days with ozone exceeding the standard fluctuated, and days with co-pollution decreased significantly; there was a strong positive correlation between PM2.5 and ozone concentration in summer, with the highest correlation coefficient of 0.52, and a strong negative correlation in winter. ③ Comparing the meteorological conditions of typical cities during the ozone pollution period with that of the co-pollution period, the co-pollution occurred under the temperature range of 23.7-26.5℃, humidity of 48%-65%, and S-SE wind direction.

Photocatalytic hydrogen production and storage in carbon nanotubes: a first-principles study.

As it is a promising clean energy source, the production and storage of hydrogen are crucial techniques. Here, based on first-principles calculations, we proposed an integral strategy for the production and storage of hydrogen in carbon nanotubes via photocatalytic processes. We considered a core-shell structure formed by placing a carbon nitride nanowire inside a carbon nanotube to achieve this goal. Photo-generated holes on the carbon nanotube surface promote water splitting. Driven by intrinsic electrostatic field in the core-shell structures, protons produced by water splitting penetrate the carbon nanotube and react with photo-generated electrons on the carbon nitride nanowire to produce hydrogen molecules in the carbon nanotube. Because carbon nanotubes have high hydrogen storage capacity, this core-shell structure can serve as a candidate system for photocatalytic water splitting and safe hydrogen storage.

Rational Design of Black Phosphorus-Based Direct Z-Scheme Photocatalysts for Overall Water Splitting: The Role of Defects.

Black phosphorus (BP) has received increasing interest as a promising photocatalyst for water splitting. Nevertheless, exploring the underlying hydrogen evolution reaction (HER) mechanism and improving the water oxidizing ability remains an urgent task. Here, using first-principles calculations, we uncover the role of point defects in improving the HER activity of BP photocatalysts. We demonstrate that the defective phosphorene can be effectively activated by the photoinduced electrons under solar light, exhibiting high HER catalytic activity in a broad pH range (0-10). Besides, we propose that the direct Z-scheme in the defective BP/SnSe2 heterobilayer is quite feasible for photocatalytic overall water splitting. This mechanism could be further verified based on the excited state dynamics method. The role of point defects in the photocatalytic mechanism provides useful insights for the development of BP photocatalysts.

The proportion of HIV disclosure to sexual partners among people diagnosed with HIV in China: A systematic review and meta-analysis.

Background: Sexual behavior is one of the main routes of HIV/AIDS spread. HIV disclosure to sexual partners has been confirmed to be an important strategy for HIV/AIDS prevention and control. We conducted a systematic review and meta-analysis to pool proportions and characteristics of HIV disclosure to sexual partners among people diagnosed with HIV in China. Methods: We searched eight databases and extracted the data on HIV disclosure to partners. Heterogeneity of the data was tested with I 2. Published bias subjectively and objectively analyzed through the funnel plot and Egger's regression test. Subgroup analyses were performed to explore the variation in the proportion by sexual partnership types (unclassified, regular, casual sexual partners), whether being men who have sex with men (MSM), and when to diagnose. The sources of heterogeneity were analyzed. Sensitivity analysis was carried out to evaluate the stability of the results. Results: Out of 3,698 studies, 44 were included in the review; 11 targeted on MSM. The pooled proportion of HIV disclosure to sexual partners was 65% (95% CI: 56%-75%; 34 studies). Sub-group analyses indicated the proportions of HIV disclosure to regular, casual and unclassified sexual partners were 63% (95% CI: 45%-81%; 31 studies), 20% (95% CI: 8%-33%; nine studies), and 66% (95% CI: 59%-73%; 14 studies), respectively. Fifty-seven percent (95% CI: 45%-69%; three studies) disclosed on the day of diagnosis, 62% (95% CI: 42%-82%; four studies) disclosed within 1 month, and 39% (95% CI: 2%-77%; four studies) disclosed 1 month later. Among MSM, the disclosure to regular male partners, regular female sexual partners, spouses, and casual partner were 47% (95% CI: 29%-65%; six studies), 49% (95% CI: 33%-65%; three studies), 48% (95% CI: 18%-78%; seven studies), and 34% (95% CI: 19%-49%; four studies), respectively. Conclusions: The disclosure prevalence of people diagnosed with HIV to sexual partners still need improving in China, and it varies among partner types, key populations, and time being diagnosed. HIV disclosure strategies and procedures need to be developed more detailed and tailored based on the pain points of disclosure status, so as to ultimately prevent HIV transmission through sexual contact. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022291631, identifier: CRD42022291631.

HBO1 catalyzes lysine benzoylation in mammalian cells.

Lysine benzoylation (Kbz) is a newly discovered protein post-translational modification (PTM). This PTM can be stimulated by benzoate and contributes to gene expression. However, its regulatory enzymes and substrate proteins remain largely unknown, hindering further functional studies. Here we identified and validated the lysine acetyltransferase (KAT) HBO1 as a "writer" of Kbz in mammalian cells. In addition, we report the benzoylome in mammalian cells, identifying 1747 Kbz sites; among them at least 77 are the HBO1-targeted Kbz substrates. Bioinformatics analysis showed that HBO1-targeted Kbz sites were involved in multiple processes, including chromatin remodeling, transcription regulation, immune regulation, and tumor growth. Our results thus identify the regulatory elements of the Kbz pathway and reveal the non-canonical enzymatic activity and functions of HBO1 in cellular physiology.