Identification of Sulfur-Containing Chlorinated Paraffin Structural Analogues in Human Serum: Origination from Biotransformation or Bioaccumulation?

Chlorinated paraffins (CPs) are manufactured and used in high quantities and have diverse structural analogues. It is generally recognized that sulfur-containing structural analogues of CPs are mainly derived from sulfate-conjugated phase II metabolism. In this study, we non-targeted identified three classes of sulfur-containing CP structural analogues (CPs-S) in human serum, including 44 CP sulfates (CPs-SOH/CPs-SOH-OH), 14 chlorinated benzene sulfates (CBs-SOH), and 19 CP sulfite esters (CPs-SO/CPs-SO), which were generated during the production of commercial mixtures of CPs and, thus, bioaccumulated via environmental exposures.

Alkylphenols disrupt estrogen homeostasis via diradical cross-coupling reactions: A novel pathway of endocrine disruption.

Estrogen, being an essential class of sex hormone, is an important target of endocrine disruption chemicals. It is well known that environmental disruptors could activate or inhibit estrogen receptors, acting as agonists or antagonists, and thus affect the circulating estrogen concentrations. Here, we report enzyme-mediated diradical cross-coupling reactions between alkylphenols (e.

Strategies for the Discovery of Oxazolidinone Antibacterial Agents: Development and Future Perspectives.

Oxazolidinones represent a significant class of synthetic bacterial protein synthesis inhibitors that are primarily effective against Gram-positive bacteria. The commercial success of linezolid, the first FDA-approved oxazolidinone antibiotic, has motivated researchers to develop more potent oxazolidinones by employing various drug development strategies to fight against antimicrobial resistance, some of which have shown promising results. Thus, this Perspective aims to discuss the strategies employed in constructing oxazolidinone-based antibacterial agents and summarize recent advances in discovering oxazolidinone antibiotics to provide valuable insights for potentially developing next-generation oxazolidinone antibacterial agents or other pharmaceuticals.

Alpha lipoic acid ameliorates motor deficits by inhibiting ferroptosis in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease. Ferroptosis shares several features with PD pathophysiology, and anti-ferroptosis molecules are neuroprotective in PD animal models. As an antioxidant and iron chelating agent, alpha lipoic acid (ALA) has a neuroprotective effect on PD; however, the influence of ALA on ferroptosis in PD remains unclear.

Flap perfusion assessment with indocyanine green angiography in deep inferior epigastric perforator flap breast reconstruction: A systematic review and meta-analysis.

Background: Indocyanine green angiography (ICG-A) has been widely applied for intraoperative flap assessment in DIEP flap breast reconstruction. However, the beneficial effect of ICG-A in DIEP flap breast reconstruction is still uncertain and no standardized protocol is available. This study aims to analyze the clinical outcome and comprehensively review protocols of this field.

Enzyme-Catalyzed Hydrogen-Deuterium Exchange between Environmental Pollutants and Enzyme-Regulated Endogenous Metabolites.

Environmental pollutants can disrupt the homeostasis of endogenous metabolites in organisms, leading to metabolic disorders and syndromes. However, it remains highly challenging to efficiently screen for critical biological molecules affected by environmental pollutants. Herein, we found that enzyme could catalyze hydrogen-deuterium (H-D) exchange between a deuterium-labeled environmental pollutant [D-bis(2-ethylhexyl) phthalate (D-DEHP)] and several groups of enzyme-regulated metabolites [cardiolipins (CLs), monolysocardiolipins (MLCLs), phospholipids (PLs), and lysophospholipids (LPLs)].

TrDosePred: A deep learning dose prediction algorithm based on transformers for head and neck cancer radiotherapy.

Background: Intensity-Modulated Radiation Therapy (IMRT) has been the standard of care for many types of tumors. However, treatment planning for IMRT is a time-consuming and labor-intensive process.

Purpose: To alleviate this tedious planning process, a novel deep learning based dose prediction algorithm (TrDosePred) was developed for head and neck cancers.

SIGIRR deficiency contributes to CD4 T cell abnormalities by facilitating the IL1/C/EBPβ/TNF-α signaling axis in rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a complex autoimmune disease with multiple etiological factors, among which aberrant memory CD4 T cells activation plays a key role in the initiation and perpetuation of the disease. SIGIRR (single immunoglobulin IL-1R-related receptor), a member of the IL-1 receptor (ILR) family, acts as a negative regulator of ILR and Toll-like receptor (TLR) downstream signaling pathways and inflammation. The aim of this study was to investigate the potential roles of SIGIRR on memory CD4 T cells in RA and the underlying cellular and molecular mechanisms.

Application of α-Syn Real-Time Quaking-Induced Conversion for Brain and Skin Specimens of the Chinese Patients With Parkinson's Disease.

The real-time quaking-induced conversion (RT-QuIC) assay has been developed and used as an diagnostic tool for Parkinson's disease (PD). In this study, we established α-Syn RT-QuIC using recombinant human α-Syn as the substrate. All 5 brain homogenates of neuropathological PD cases and 13 skin homogenates of clinical PD cases showed positive results, whereas all the samples of negative controls remain negative.

A PD-L1 and VEGFR2 dual targeted peptide and its combination with irradiation for cancer immunotherapy.

Although the blockade of immune checkpoint PD-1/PD-L1 has achieved great success, the lack of tumor-infiltrating immune cells and PD-L1 expression in the tumor microenvironment results in a limited response in certain tumor types. Thus, rational and optimal combination strategies were urgently needed. The combination of PD-1/PD-L1 blockade and anti-angiogenic therapy has been reported to have great potential.

Analysis of Granulocyte-Macrophage Colony-Stimulating Factor-Producing T Helper Cells in a Mouse Model of Contact Hypersensitivity.

Parallel to traditional Th1/Th2/Th17/Treg lineages, granulocyte-macrophage colony-stimulating factor-producing T helper (Th-GM) cells have been identified as a distinct subset of T helper cells (GM-CSF IFN-γ IL-17A IL-22 effector CD4 T cells) in human and mice. Contact hypersensitivity (CHS) is considered an excellent animal model for allergic contact dermatitis (ACD) in human, manifesting an intact T cell-mediated immune response. To provide a standardized and comprehensive assay to analyze the Th-GM cell subset in the T cell-dependent immune response in vivo, a murine CHS model was induced by sensitization/challenge with a reactive, low-molecular-weight, organic hapten, 2,4-dinitrofluorobenzene (DNFB).

Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy.

Strategies boosting both innate and adaptive immunity have great application prospects in cancer immunotherapy. Antibodies dual blocking the innate checkpoint CD47 and adaptive checkpoint PD-L1 or TIGIT could achieve durable anti-tumor effects. However, a small molecule dual blockade of CD47/SIRPα and TIGIT/PVR pathways has not been investigated.

CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy.

Background: Immunotherapy has achieved remarkable advances via a variety of strategies against tumor cells that evade immune surveillance. As important innate immune cells, macrophages play important roles in maintaining homeostasis, preventing pathogen invasion, resisting tumor cells and promoting adaptive immune response. CD47 is found to be overexpressed on tumor cells and act as a don't eat me' signal, which contributes to immune evasion.

Repositioning liothyronine for cancer immunotherapy by blocking the interaction of immune checkpoint TIGIT/PVR.

Background: Inhibitors targeting immune checkpoint were proved effective in cancer immunotherapy, such as PD-1/PD-L1 blockade. The novel immune checkpoint TIGIT/PVR plays critical roles in suppressing the anti-tumor effects of CD8 T and NK cells, and dual blockade of TIGIT/PVR and PD-1/PD-L1 by antibody can elicit synergistic effects in tumor models and clinical trials. However, small molecules for TIGIT/PVR blockade have not been investigated.

Alpha-Lipoic Acid Mediates Clearance of Iron Accumulation by Regulating Iron Metabolism in a Parkinson's Disease Model Induced by 6-OHDA.

The disruption of neuronal iron homeostasis and oxidative stress are related to the pathogenesis of Parkinson's disease (PD). Alpha-lipoic acid (ALA) is a naturally occurring enzyme cofactor with antioxidant and iron chelator properties and has many known effects. ALA has neuroprotective effects on PD.

Positron emission computed tomography/single photon emission computed tomography in Parkinson disease.

Parkinson disease (PD) is the second-most common neurodegenerative disorder. Its main pathological mechanism is the selective degeneration and deletion of dopaminergic neurons in the dense part of the substantia nigra and the damage of dopaminergic neurons caused by the abnormal deposition of a Lewy body, leading to a decreased dopamine level. Positron emission computed tomography (PET)/single photon emission computed tomography (SPECT) is a molecular imaging technology that can directly or indirectly reflect changes in molecular levels by using a specific tracer.

Physical dosimetry reconstructions of significant radiation exposure at an industrial accelerator facility in Tianjin (China).

The goal of this thesis is to estimate the physical radiation doses for two victims who were accidently exposed to an industrial electron beam at an industrial accelerator facility on 7 July 7 2016 in Tianjin, China. On the basis of the radiation source parameters, irradiation situation and irradiation time, physical dose reconstruction was carried out at the accident site by using a Bottle-Manikin-Absorption (BOMAB) phantom and an Alderson Radiation Therapy (ART) phantom. With thermoluminscent dosimeters (TLDs), skin estimation was conducted for the feet, calves, upper arms, left side of the body and neck, and the mean dose was estimated to be 14.

[Alpha-lipoic acid inhibits the expression of α-synuclein in PC12 cells induced by 6-hydroxydopamine and its mechanism].

Objective To investigate the effects of α-lipoic acid (α-LA) on the expression of α-synuclein(α-syn)in cellular models of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) and its mechanism. Methods PC12 cells were induced by 6-OHDA to establish the cellular models of PD, which was treated with α-LA. Cell viability was detected using MTT assay.

Source identification of PM at a port and an adjacent urban site in a coastal city of China: Impact of ship emissions and port activities.

Daily PM samples were collected simultaneously at an urban site (UB) and a nearby port-industrial site (PI) on the coast of southeastern China from April 2015 to January 2016. The PM mass concentration at the PI (51.9μgm) was significantly higher than that at the UB.

[Mechanism of α-lipoic acid promoting iron efflux in substantia nigra cells of Parkinson's disease rats].

Objective To observe the effect of α-lipoic acid (α-LA) on the expressions of iron regulatory protein 2 (IRP2) and ferroportin1 (FP1) in substantia nigra of rats with Parkinson's disease (PD) and explore the mechanism by which α-LA regulates iron efflux in substantia nigra cells of PD rat models. Methods Sixty healthy male SD rats were randomly divided into a sham group (n=15) and a model group (n=45). To establish the PD model, the rats of the model group were injected with 6-hydroxydopamine (6-OHDA) into their right striatum by the stereotactic technique, and the sham operation group was injected with the same dose of normal saline.