A recombinant L-threonine aldolase with high catalytic efficiency for the asymmetric synthesis of L-threo-phenylserine and L-threo-4-fluorophenylserine.

Objectives: To develop robust variants of L-threonine aldolases (L-TAs), potent catalysts for synthesizing asymmetric β-hydroxy-α-amino acids, it is necessary to identify critical residues beyond the known active site residues.

Results: Through virtual screening, a neglected residue Asn305, was identified as critical for catalytic efficiency. Subsequent site-saturation mutagenesis led to a potent variant N305R which exhibited excellent conversions of 88% (87%) and 80% (94%) for the synthesis of L-threo-phenylserine and L-threo-4-fluorophenylserine respectively.

Synthesis of TUDCA from chicken bile: immobilized dual-enzymatic system for producing artificial bear bile substitute.

Bear bile, a valuable animal-derived medicinal substance primarily composed of tauroursodeoxycholic acid (TUDCA), is widely distributed in the medicinal market across various countries due to its significant therapeutic potential. Given the extreme cruelty involved in bear bile extraction, researchers are focusing on developing synthetic bear bile powder as a more humane alternative. This review presents an industrially practical and environmentally friendly process for producing an artificial substitute for bear bile powder using inexpensive and readily available chicken bile powder through an immobilized 7α-,7β-HSDH dual-enzymatic syste.

Discovery and optimization of novel 4-morpholinothieno[3,2-d]pyrimidine derivatives as potent BET inhibitors for cancer therapy.

The identification of structurally novel and potently active BET inhibitors represents a significant advancement in the field of anticancer therapeutics. In the present investigation, leveraging the outcomes of previous screening endeavors, we successfully optimized and synthesized a novel series of bromodomain and extra-terminal (BET) inhibitors with a 4-morpholinothieno[3,2-d]pyrimidine structure. Among the synthesized compounds, compound 6c emerged as a promising candidate, exhibiting exceptional inhibitory activities against various BET isoform proteins, with IC values ranging from 3.

Targeting PYK2 with heterobifunctional T6BP helps mitigate MASLD and MASH-HCC progression.

Background & Aims: The mechanisms underlying the regulation of hepatocyte non-receptor tyrosine kinases in metabolic dysfunction-associated steatohepatitis (MASH) remain largely unclear.

Methods: Hepatocyte-specific overexpression or deletion and anti-protein tyrosine kinase 2 beta (PYK2) or anti-TRAF6-binding protein (T6BP) crosslinking were utilized to study fatty liver protection by T6BP. A P-PTC (peptide-proteolysis targeting chimera) degrades PYK2 to block MASH progression.

Mannitol mediates the mummification behavior of larvae infected with .

Introduction: Parasites can facilitate their own spread and reproduction by manipulating insect hosts behavior, as seen in the interaction between and . Infection by leads to the mummification of larvae, but the underlying mechanisms remain mysterious.

Methods: The morphology of infected larvae and fungal growth were first observed.

The role of gut microbiota in MP/NP-induced toxicity.

Microplastics (MPs) and nanoplastics (NPs) are globally recognized as emerging environmental pollutants in various environmental media, posing potential threats to ecosystems and human health. MPs/NPs are unavoidably ingested by humans, mainly through contaminated food and drinks, impairing the gastrointestinal ecology and seriously impacting the human body. The specific role of gut microbiota in the gastrointestinal tract upon MP/NP exposure remains unknown.

Rational Design of Human Hair Keratin-Driven Proteins for Hair Growth Promotion.

Keratins, the most abundant proteins in human hair, are excellent hair nutrients for growth. However, the complex components of keratin extract hinder their mechanism investigation, and the pure recombinant keratin with poor solubility limited its hair growth promotion efficiency. Here, the water-soluble recombinant keratins (RKs) of K31 and K81 are rationally designed through QTY Code methodology, which are then used to fabricate the microneedles to study the effect of keratin on hair growth.

SIPA1 promotes epithelial-mesenchymal transition in colorectal cancer through STAT3 activation.

Colorectal cancer (CRC) is the third leading cancer type worldwide and accounts for the second highest rate of cancer-related mortality. Liver metastasis significantly contributes to the mortality associated with CRC, but the fundamental mechanisms behind it remain unclear. Signal-induced proliferation-associated protein 1 (SIPA1), a GTPase activating protein, has been shown to promote metastasis in breast cancer.

Neurotransmitter acetylcholine mediates the mummification of -infected larvae.

Parasites can manipulate host behavior to facilitate parasite transmission. One such host-pathogen interaction occurs between the fungus and the ghost moth is involved in the mummification process of infected host larvae. However, the underlying molecular and chemical mechanism for this phenomenon is unknown.

Purse-string suture with nylon cords and metal clips for the treatment of duodenal fistulae under the endoscope: a case report.

Purse-string suture with nylon cords and metal clips under the endoscope is a novel therapeutic technique which is minimally invasive and it is particularly indicated for the closure and repair of gastrointestinal fistula or perforations such as duodenal fistulae. Duodenal fistulae are often caused by medical manipulation, disease progression or trauma. Once this occurs, it leads to a series of pathophysiologic changes and a variety of complications.

Unraveling the Pathogenesis of Post-Stroke Depression in a Hemorrhagic Mouse Model through Frontal Lobe Circuitry and JAK-STAT Signaling.

Post-stroke depression is a common complication that imposes significant burdens and challenges on patients. The occurrence of depression is often associated with frontal lobe hemorrhage, however, current understanding of the underlying mechanisms remains limited. Here, the pathogenic mechanisms associated with the circuitry connectivity, electrophysiological alterations, and molecular characteristics are investigated related to the frontal lobe in adult male mice following unilateral injection of blood in the medial prefrontal cortex (mPFC).

Revisiting the quasi-aromaticity in polynuclear metal chalcogenide clusters and their derivative "cluster-assembly" crystalline structures.

The concept of aromaticity is primarily invented to account for the high stability of conjugated organic compounds that possess a specific structural and chemical stability with (4 + 2) π electrons. In 1988, quasi-aromaticity was theoretically proposed for the MoS core in the Mo(μ-S)(μ-S)(χ-dtp)(μ-dtp) L compound (χ: chelating ligand; dtp: (EtO)PS) illustrated by canonical molecular orbitals. However, the origin of the quasi-aromaticity and chemical bonding remains ambiguous, lacking a thorough analysis in terms of stability and quantitative measurement of the aromatic character.

Novel approaches in IBD therapy: targeting the gut microbiota-bile acid axis.

Inflammatory bowel disease (IBD) is a chronic and recurrent condition affecting the gastrointestinal tract. Disturbed gut microbiota and abnormal bile acid (BA) metabolism are notable in IBD, suggesting a bidirectional relationship. Specifically, the diversity of the gut microbiota influences BA composition, whereas altered BA profiles can disrupt the microbiota.

Macrophorins H and L, two new HMG-conjugate macrophorins from rihzospheric sp. NX-05-G-3.

Macrophorins H () and L (), two rare HMG-conjugate macrophorins along with three known macrophorins (-), three DMOA-derived meroterpenoids (-) and two ergosterol derivates (-) were isolated from sterilized rice medium cultured sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR.

Unveiling the Hidden Impact: Hematoma Volumes Unravel Circuit Disruptions in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) imposes a significant burden on patients, and the volume of hematoma plays a crucial role in determining the severity and prognosis of ICH. Although significant recent progress has been made in understanding the cellular and molecular mechanisms of surrounding brain tissue in ICH, our current knowledge regarding the precise impact of hematoma volumes on neural circuit damage remains limited. Here, using a viral tracing technique in a mouse model of striatum ICH, two distinct patterns of injury response were observed in upstream connectivity, characterized by both linear and nonlinear trends in specific brain areas.

Human brain organoid: trends, evolution, and remaining challenges.

Advanced brain organoids provide promising platforms for deciphering the cellular and molecular processes of human neural development and diseases. Although various studies and reviews have described developments and advancements in brain organoids, few studies have comprehensively summarized and analyzed the global trends in this area of neuroscience. To identify and further facilitate the development of cerebral organoids, we utilized bibliometrics and visualization methods to analyze the global trends and evolution of brain organoids in the last 10 years.

Engineered keratin/bFGF hydrogel to promote diabetic wound healing in rats.

Keratin materials are promising in wound healing acceleration, however, it is a challenge for the keratin to efficiently therapy the impaired wound healing, such as diabetic foot ulcers. Here, we report a keratin/bFGF hydrogel for skin repair of chronic wounds in diabetic rats based on their characteristics of extracellular matrix and growth factor degradation in diabetic ulcer. Recombinant keratin 31 (K31), the most abundant keratin in human hair, exhibited the highly efficient performances in cell adhesion, proliferation and migration.

Engineering the cofactor binding site of 7α-hydroxysteroid dehydrogenase for improvement of catalytic activity, thermostability, and alteration of substrate preference.

Hydroxysteroid dehydrogenases (HSDHs) are crucial for bile acid metabolism and influence the size of the bile acid pool and gut microbiota composition. HSDHs with high activity, thermostability, and substrate selectivity are the basis for constructing engineered bacteria for disease treatment. In this study, we designed mutations at the cofactor binding site involving Thr15 and Arg16 residues of HSDH St-2-2.

The Integration of the Metabolome and Transcriptome for Lindl. in Response to Methyl Jasmonate.

Lindl., as an endangered medicinal plant within the genus , is widely distributed in southwestern China and has important ecological and economic value. There are a variety of metabolites with pharmacological activity in .

Smart Physical-Based Transdermal Drug Delivery System:Towards Intelligence and Controlled Release.

Transdermal drug delivery systems based on physical principles have provided a stable, efficient, and safe strategy for disease therapy. However, the intelligent device with real-time control and precise drug release is required to enhance treatment efficacy and improve patient compliance. This review summarizes the recent developments, application scenarios, and drug release characteristics of smart transdermal drug delivery systems fabricated with physical principle.

Multifunctional Novel Nanoplatform for Effective Synergistic Chemo-Photodynamic Therapy of Breast Cancer by Enhancing DNA Damage and Disruptions of Its Reparation.

Photodynamic therapy (PDT) is an effective noninvasive therapeutic strategy that has been widely used for anti-tumor therapy by the generation of excessive highly cytotoxic ROS. However, the poor water solubility of the photosensitizer, reactive oxygen species (ROS) depleting by high concentrations of glutathione (GSH) in the tumor microenvironment and the activation of DNA repair pathways to combat the oxidative damage, will significantly limit the therapeutic effect of PDT. Herein, we developed a photosensitizer prodrug (CSP) by conjugating the photosensitizer pyropheophorbide a (PPa) and the DNA-damaging agent Chlorambucil (Cb) with a GSH-responsive disulfide linkage and demonstrated a multifunctional co-delivery nanoplatform ( nanoparticles (NPs)) together with DSPE-PEG and PARP inhibitor Olaparib (Ola).

Tripartite motif containing 26 prevents steatohepatitis progression by suppressing C/EBPδ signalling activation.

Currently potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) and NASH-related pathopoiesis have failed to achieve expected therapeutic efficacy due to the complexity of the pathogenic mechanisms. Here we show Tripartite motif containing 26 (TRIM26) as a critical endogenous suppressor of CCAAT/enhancer binding protein delta (C/EBPδ), and we also confirm that TRIM26 is an C/EBPδ-interacting partner protein that catalyses the ubiquitination degradation of C/EBPδ in hepatocytes. Hepatocyte-specific loss of Trim26 disrupts liver metabolic homeostasis, followed by glucose metabolic disorder, lipid accumulation, increased hepatic inflammation, and fibrosis, and dramatically facilitates NASH-related phenotype progression.