Botulinum neurotoxins exploit host digestive proteases to boost their oral toxicity via activating OrfXs/P47.

Botulinum neurotoxins (BoNTs) rank among the most potent toxins and many of them are produced by bacteria carrying the orfX gene cluster that also encodes four nontoxic proteins (OrfX1, OrfX2, OrfX3 and P47). The orfX gene cluster is also found in the genomes of many non-BoNT-producing bacteria, often alongside genes encoding oral insecticidal toxins. However, the functions of these OrfXs and P47 remain elusive.

Bile acid in drainage fluid for early diagnosis of anastomotic leakage and safe discharge after minimally invasive rectal cancer resection: A prospective cohort study.

Background: This study was designed to evaluate the diagnostic value of bile acid levels in drainage fluid for early prediction and exclusion of anastomotic leakage, and assess the performance in allowing a safe discharge.

Methods: This prospective single-center study was conducted in patients diagnosed with rectal cancer who had received minimally invasive anterior resection consecutively from December 2021 to March 2024. Bile acid in drainage fluid, C-reactive protein, and procalcitonin in serum were measured on the third and fifth day after surgery.

Survey on the distribution of medical imaging frequencies and dose levels for CT examinations in a comprehensive hospital in Shanghai.

With the continuous advancement and clinical application of CT technology, the increasing collective dose burden from CT scans and associated potential health risks have become significant concerns in radiation protection. Current research increasingly focuses on the cumulative effective dose (CED) resulting from multiple CT scans, often revealing patients with high CEDs, even exceeding 100 mSv. However, reports on CEDs from multiple CT scans in China are scarce.

Age-based diagnostic reference levels and achievable doses for paediatric CT: a survey in Shanghai, China.

Computed tomography (CT) is extensively utilised in medical diagnostics due to its notable radiographic superiority. However, the cancer risk associated with CT examinations, particularly in children, is of significant concern. The assessment of cancer risk relies on the radiation dose to examinees.

NTNH protein: more than a bodyguard for botulinum neurotoxins.

As one of the most fatal substances, botulinum neurotoxins (BoNTs) have never acted solo to accomplish their formidable missions. Most notably, nontoxic nonhemagglutinin (NTNH), a protein co-secreted with BoNT by bacteria, plays critical roles to stabilize and protect BoNT by tightly associating with it to form the minimal progenitor toxin complex (M-PTC). A new cryo-EM structure of the M-PTC of a BoNT-like toxin from Weissella oryzae (BoNT/Wo) reveals similar assembly modes between M-PTC/Wo and that of other BoNTs, yet also reveals some unique structural features of NTNH/Wo.

Crystal structures of OrfX1, OrfX2 and the OrfX1-OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1.

Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A-G encoded in two types of gene clusters (ha and orfX) in BoNT-producing clostridia. The ha cluster encodes four non-toxic neurotoxin-associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX-type NAPs remain largely unknown.

Blind detection of circular image rotation angle based on ensemble transfer regression and fused HOG.

Introduction: Aiming at the problems of low accuracy in estimating the rotation angle after the rotation of circular image data within a wide range (0°-360°) and difficulty in blind detection without a reference image, a method based on ensemble transfer regression network, fused HOG, and Rotate Loss is adopted to solve such problems.

Methods: The proposed Rotate Loss was combined to solve the angle prediction error, especially the huge error when near 0°. Fused HOG was mainly used to extract directional features.

Impact of Protein Nitration on Influenza Virus Infectivity and Immunogenicity.

Influenza viruses are deadly respiratory pathogens of special importance due to their long history of global pandemics. During influenza virus infections, the host responds by producing interferons, which activate interferon-stimulated genes (ISGs) inside target cells. One of these ISGs is inducible nitric oxide synthase (iNOS).

Structure of DNMT3B homo-oligomer reveals vulnerability to impairment by ICF mutations.

DNA methyltransferase DNMT3B plays an essential role in establishment of DNA methylation during embryogenesis. Mutations of DNMT3B are associated with human diseases, notably the immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome. How ICF mutations affect DNMT3B activity is not fully understood.

DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation.

DNA methylation and trimethylated histone H4 Lysine 20 (H4K20me3) constitute two important heterochromatin-enriched marks that frequently cooperate in silencing repetitive elements of the mammalian genome. However, it remains elusive how these two chromatin modifications crosstalk. Here, we report that DNA methyltransferase 1 (DNMT1) specifically 'recognizes' H4K20me3 via its first bromo-adjacent-homology domain (DNMT1).

Domino Effect: Gold Electrocatalyzing Lithium Reduction to Accelerate Nitrogen Fixation.

Green production of NH , especially the Li-mediated electrochemical N reduction reaction (NRR) in non-aqueous solutions, is attracting research interest. Controversies regarding the NRR mechanism greatly impede its optimization and wide applications. To understand the electrocatalytic process, we treated Au coated carbon fibrous paper (Au/CP) as the model catalyst.

Short-term outcomes of pelvic floor peritoneum closure in endoscopic low anterior resection of rectal cancer: A propensity score matching analysis.

Background: The efficacy of pelvic floor peritoneum closure (PC) during endoscopic low anterior resection (E-LAR) of rectal cancer remains unclear. This study aimed to clarify whether pelvic floor PC affected short-term outcomes.

Methods: The study group comprised patients with the pathologically confirmed diagnosis of rectal cancer who underwent E-LAR with pelvic floor PC or with no PC (NPC) between January 2013 and December 2018 in Southwest Hospital.

Structural basis for STAT2 suppression by flavivirus NS5.

Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human STAT2 (hSTAT2) in complex with the non-structural protein 5 (NS5) of Zika virus (ZIKV) and dengue virus (DENV), revealing two-pronged interactions between NS5 and hSTAT2. First, the NS5 methyltransferase and RNA-dependent RNA polymerase (RdRP) domains form a conserved interdomain cleft harboring the coiled-coil domain of hSTAT2, thus preventing association of hSTAT2 with interferon regulatory factor 9.

Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation.

In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader.

The Agpat4/LPA axis in colorectal cancer cells regulates antitumor responses via p38/p65 signaling in macrophages.

Lipid metabolic reprogramming plays an essential role in regulating the progression of colorectal cancer (CRC). However, the effect of lysophosphatidic acid (LPA) metabolism on CRC development is incompletely characterized. Here, we compared the mRNA levels of human CRC tissues to those of paracarcinoma tissues and focused on the notably enriched LPA metabolic pathways.

Chemical Proteomic Profiling of Lysophosphatidic Acid-Binding Proteins.

Lysophosphatidic acid (LPA) is an endogenous cell signaling molecule, and dysregulation of LPA signaling pathways is accompanied by several types of cancer. Herein, we developed a chemical proteomic method for the proteome-wide identification of LPA-binding proteins. The method involves the synthesis of a desthiobiotin-conjugated LPA acyl phosphate probe for the covalent labeling, enrichment, and subsequent LC-MS/MS identification of LPA-binding proteins at the proteome-wide level.

A DNA aptamer for binding and inhibition of DNA methyltransferase 1.

DNA methyltransferases (DNMTs) are enzymes responsible for establishing and maintaining DNA methylation in cells. DNMT inhibition is actively pursued in cancer treatment, dominantly through the formation of irreversible covalent complexes between small molecular compounds and DNMTs that suffers from low efficacy and high cytotoxicity, as well as no selectivity towards different DNMTs. Herein, we discover aptamers against the maintenance DNA methyltransferase, DNMT1, by coupling Asymmetrical Flow Field-Flow Fractionation (AF4) with Systematic Evolution of Ligands by EXponential enrichment (SELEX).

Dissect the DNMT3A- and DNMT3B-mediated DNA Co-methylation through a Covalent Complex Approach.

DNA methylation plays a critical role in regulating gene expression, genomic stability, and cell fate commitment. Mammalian DNA methylation, which mostly occurs in the context of CpG dinucleotide, is installed by two denovo DNA methyltransferases, DNMT3A and DNMT3B. Oligomerization of DNMT3A and DNMT3B permits both enzymes to comethylate two CpG sites located on the same DNA substrates.

Structure and regulation of ZCCHC4 in mA-methylation of 28S rRNA.

N-methyladenosine (mA) modification provides an important epitranscriptomic mechanism that critically regulates RNA metabolism and function. However, how mA writers attain substrate specificities remains unclear. We report the 3.

Structural Basis of DNMT1 and DNMT3A-Mediated DNA Methylation.

DNA methylation, one of the major epigenetic mechanisms, plays critical roles in regulating gene expression, genomic stability and cell lineage commitment. The establishment and maintenance of DNA methylation in mammals is achieved by two groups of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B, which are responsible for installing DNA methylation patterns during gametogenesis and early embryogenesis, and DNMT1, which is essential for propagating DNA methylation patterns during replication. Both groups of DNMTs are multi-domain proteins, containing a large N-terminal regulatory region in addition to the C-terminal methyltransferase domain.

2D bismuthene fabricated via acid-intercalated exfoliation showing strong nonlinear near-infrared responses for mode-locking lasers.

The rediscovery of black phosphorus (BP) has expanded the 2D family into Group 15 (Nitrogen Group) elements, among which bismuthene is the latest member with extraordinary opto-electronic, catalytic and biocompatible properties and potential as a 2D topological insulator. However, bulk Bi is not easily mechanically exfoliated as its counterpart of BP. Thus, to date, the reports on 2D Bi fabrication are rare, and investigations on its nonlinear optical properties are even less.

An all-inorganic lead halide perovskite-based photocathode for stable water reduction.

Lead halide perovskites (LHPs) have been investigated for photoelectrochemical hydrogen generation from water splitting. However, the harsh requirements in preparing the environment, i.e.

Structural basis for DNMT3A-mediated de novo DNA methylation.

DNA methylation by de novo DNA methyltransferases 3A (DNMT3A) and 3B (DNMT3B) at cytosines is essential for genome regulation and development. Dysregulation of this process is implicated in various diseases, notably cancer. However, the mechanisms underlying DNMT3 substrate recognition and enzymatic specificity remain elusive.

An Intramolecular Interaction of UHRF1 Reveals Dual Control for Its Histone Association.

UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) is one of the essential components of mammalian DNA methylation machinery. Chromatin association of UHRF1 is controlled via an interplay between its intramolecular interaction and dual recognition of histone H3 trimethylated at lysine 9 (H3K9me3) and hemimethylated DNA. Here, we report the crystal structure of the N-terminal tandem Tudor domain (TTD) of UHRF1 in complex with the C-terminal polybasic region (PBR).