4-Eth­oxy­anilinium chloride

The title compound, C8H12NO+·Cl−, consists of an almost planar protonated 4-eth­oxy­anilinium cation with the N atom showing the biggest deviation from the plane formed by all non-H atoms of the cation [0.066 (1) Å]. In the crystal, N—H⋯Cl hydrogen bonds link cations and anions into chains along the a axis. Additional C—H⋯π and π–π inter­actions [centroid–centroid distance = 4.873 (2) Å] stabilize the crystal structure

Isopropyl 3-(3,4-dihydroxy­phen­yl)-2-hydroxy­propanoate

The title compound, C12H16O5, is a derivative of β-(3,4-dihydroxy­phen­yl)-α-hydr­oxy acid. The crystal packing is stabilized by inter­molecular O—H⋯O hydrogen bonds

Surface-exposed loops L7 and L8 of Haemophilus (Glaesserella) parasuis OmpP2 contribute to the expression of proinflammatory cytokines in porcine alveolar macrophages

International audienceOuter membrane protein P2 (OmpP2) of the virulent Haemophilus (Glaesserella) parasuis has been shown to induce the release of proinflammatory cytokines. The OmpP2 protein is composed of eight or nine surface-exposed loops, but it is unclear which of them participates in the OmpP2-induced inflammatory response. In this study, we synthesized linear peptides corresponding to surface-exposed loops L1–L8 of OmpP2 from the virulent H. parasuis SC096 strain to stimulate porcine alveolar macrophages (PAMs) in vitro. We found that both L7 and L8 significantly upregulated the mRNA expression of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-17, and IL-23 and the chemokines CCL-4 and CCL-5 in a time- and dose-dependent manner. Additionally, we constructed ompP2ΔLoop7 and ompP2ΔLoop8 mutant SC096 strains and extracted their native OmpP2 proteins to stimulate PAMs. These mutant proteins induced significantly less mRNA expression of inflammatory cytokines than SC096 OmpP2. Next, the amino acid sequences of L7 and L8 from 15 serovars of H. parasuis OmpP2 were aligned. These sequences were relatively conserved among the most virulent reference strains, suggesting that L7 and L8 are the most active peptides of the OmpP2 protein. Furthermore, L7 and L8 significantly upregulated the NF-κB and AP-1 activity levels based on luciferase reporter assays in a dose-dependent manner. Therefore, our results demonstrated that both surface-exposed loops L7 and L8 of H. parasuis OmpP2 induced the expression of proinflammatory cytokines possibly by activating the NF-κB and MAPK signalling pathways in cells infected by H. parasuis

Modeling and Simulating Dynamics of Complete- and Poor-Response Chronic Hepatitis B Chinese Patients for Adefovir and Traditional Chinese Medicine Plus Adefovir Therapy

ChiCTR-TRC-11001263 study was the first large-scale double-blind randomized placebo-controlled traditional Chinese medicines (TCMs) and adefovir (ADV) antihepatitis B virus (HBV) infection trial in the world. A total of 560 hepatitis B e antigen- (HBeAg-) positive Chinese patients with chronical HBV were randomly classified, in 1 : 1 ratio, into two groups: experimental group (EXG) receiving TCMs + ADV and controlled group (CTG) receiving ADV + TCM-placebo treatment for 48 weeks. This paper introduces two models to model and simulate the evolutions of dynamics for the complete-response patients and the poor-response patients in EXG and CTG, respectively. The stimulated mean HBV DNA and alanine aminotransferase (ALT) levels were close to the patients’ experimental data. Analysis and simulations suggest that the activated patients’ immune functions by TCMs + ADV may not only clear infected hepatocytes, but also clear HBV, which made the complete-response patients’ mean serum HBV DNA levels in EXG reduce rapidly 12 weeks’ earlier than the ones in CTG. One can assume that both the TCMs and ADV have the function of preventing complete-response patients’ infected hepatocytes from being injured by cytotoxic T lymphocytes (CTLs); the patients’ activated immune cells may also block HBV replications

Making 2‐D Materials Mechanochemically by Twin‐Screw Extrusion:Continuous Exfoliation of Graphite to Multi‐Layered Graphene

Mechanochemistry has developed rapidly in recent years for efficient chemicals and materials synthesis. Twin screw extrusion (TSE) is a particularly promising technique in this regard because of its continuous and scalable nature. A key aspect of TSE is that it provides high shear and mixing. Because of the high shear, it potentially also offers a way to delaminate 2‐D materials. Indeed, the synthesis of 2‐D materials in a scalable and continuous manor remains a challenge in their industrialization. Here, as a proof‐of‐principle, the automated, continuous mechanochemical exfoliation of graphite to give multi‐layer graphene (MLG, ≈6 layers) by TSE is demonstrated. To achieve this, a solid‐and‐liquid‐assisted extrusion (SLAE) process is developed in which organic additives such as pyrene are rendered liquid due to the high temperatures used, to assist with the exfoliation, and simultaneously solid sodium chloride is used as a grinding aid. This gave MLG in high yield (25 wt%) with a short residence time (8 min) and notably with negligible evidence for structural deterioration (defects or oxidation)

PI3K/Akt pathway: a potential therapeutic target for chronic pain

Chronic pain is among the most disabling and costly disorders, with prevalence ranging from 10% to 55%. However, current therapeutic strategies for chronic pain are unsatisfactory due to our poor understanding of its mechanisms. Thus, novel therapeutic targets need to be found in order to improve these patients' quality of life. PI3K and its downstream Akt are widely expressed in the spinal cord, particularly in the laminae I-IV of the dorsal horn, where nociceptive C and Aδ fibers of primary afferents principally terminate. Recent studies have demonstrated their critical roles in the development and maintenance of chronic pain. In this review, we summarized the roles and mechanisms of PI3K/Akt pathway in the progression of chronic pain through sciatic nerve injury, diabetic neuropathy, spinal cord injury, bone cancer, opioid tolerance, or opioid-induced hyperalgesia

FIMO: A Challenge Formal Dataset for Automated Theorem Proving

We present FIMO, an innovative dataset comprising formal mathematical problem statements sourced from the International Mathematical Olympiad (IMO) Shortlisted Problems. Designed to facilitate advanced automated theorem proving at the IMO level, FIMO is currently tailored for the Lean formal language. It comprises 149 formal problem statements, accompanied by both informal problem descriptions and their corresponding LaTeX-based informal proofs. Through initial experiments involving GPT-4, our findings underscore the existing limitations in current methodologies, indicating a substantial journey ahead before achieving satisfactory IMO-level automated theorem proving outcomes