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1.
Food Chem X ; 23: 101553, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-38984291

ABSTRACT

Piling fermentation (PF) is crucial for Pu-erh tea aroma, yet its microbial and moist-heat impact on aroma quality is poorly understood. Solid-phase microextraction, solvent-assisted flavor evaporation, and gas chromatography-mass spectrometry were used to detected and analyses the samples of sun-green green tea, sterile PF and spontaneous PF. Microbiological action promotes the formation of stale aromas. Moist-heat action promotes the formation of plum-fragrance and sweet aroma. 20 microbial markers and 28 moist-heat markers were screened from 184 volatile components. Combining odor activity values and gas chromatography-olfactometry, 22 aroma-active compounds were screened (1,2,3-trimethoxybenzene, linalool, 1,2,4-trimethoxybenzene …), and analyzed during PF processing. Aroma omission and addition experiments verified its importance. Gallic acid addition experiments successfully verified that microorganisms are the main contributors to the synthesis of methoxybenzenes. Finally, Blastobotrys, Rasamsonia, and Thermomyces showed positive correlation with the synthesis of 1-ethyl-4-methoxybenzene, 1,2,4-trimethoxybenzene, 1,2,3-trimethoxybenzene, and 1,2-dimethoxybenzene. The formation mechanism of Pu-erh tea's aroma was clarified. Exploring microbial and moist-heat effects on Pu-erh tea volatiles and understanding the methoxybenzene formation mechanism using molecular sensory science.

2.
Sci Total Environ ; 947: 174409, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960158

ABSTRACT

Enzyme-induced carbonate precipitation (EICP) has been studied in remediation of heavy metal contaminated water or soil in recent years. This paper aims to investigate the immobilization mechanism of Zn2+, Ni2+, and Cr(VI) in contaminated sand, as well as strength enhancement of sand specimens by using EICP method with crude sword bean urease extracts. A series of liquid batch tests and artificially contaminated sand remediation experiments were conducted to explore the heavy metal immobilization efficacy and mechanisms. Results showed that the urea hydrolysis completion efficiency decreased as the Ca2+ concentration increased and the heavy metal immobilization percentage increased with the concentration of Ca2+ and treatment cycles in contaminated sand. After four treatment cycles with 0.5 mol/L Ca2+ added, the immobilization percentage of Zn2+, Ni2+, and Cr(VI) were 99.99 %, 86.38 %, and 75.18 %, respectively. The microscale analysis results presented that carbonate precipitates and metallic oxide such as CaCO3, ZnCO3, NiCO3, Zn(OH)2, and CrO(OH) were generated in liquid batch tests and sand remediation experiments. The SEM-EDS and FTIR results also showed that organic molecules and CaCO3 may adsorb or complex heavy metal ions. Thus, the immobilization mechanism of EICP method with crude sword bean urease can be considered as biomineralization, as well as adsorption and complexation by organic matter and calcium carbonate. The unconfined compressive strength of EICP-treated contaminated sand specimens demonstrated a positive correlation with the increased generation of carbonate precipitates, being up to 306 kPa after four treatment cycles with shear failure mode. Crude sword bean urease with 0.5 mol/L Ca2+ added is recommended to immobilize multiple heavy metal ions and enhance soil strength.

3.
Int J Biol Macromol ; 271(Pt 1): 132594, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821811

ABSTRACT

A lipidated polysaccharide, HDPS-2II, was isolated from the dried larva of Holotrichia diomphalia, which is used in traditional Chinese medicine. The molecular weight of HDPS-2II was 5.9 kDa, which contained a polysaccharide backbone of →4)-ß-Manp-(1 â†’ 4,6)-ß-Manp-(1 â†’ [6)-α-Glcp-(1]n â†’ 6)-α-Glcp→ with the side chain α-Glcp-(6 â†’ 1)-α-Glcp-(6 â†’ linked to the C-4 of ß-1,4,6-Manp and four types of lipid chains including 4-(4-methyl-2-(methylamino)pentanamido)pentanoic acid, 5-(3-(tert-butyl)phenoxy)hexan-2-ol, N-(3-methyl-5-oxopentan-2-yl)palmitamide, and N-(5-amino-3-methyl-5-oxopentan-2-yl)stearamide. The lipid chains were linked to C-1 of terminal α-1,6-Glcp in carbohydrate chain through diacyl-glycerol. HDPS-2II exhibited DNA protective effects and antioxidative activity on H2O2- or adriamycin (ADM)-induced Chinese hamster lung cells. Furthermore, HDPS-2II significantly ameliorated chromosome aberrations and the accumulation of reactive oxygen species (ROS), reduced γ-H2AX signaling and the expressions of NADPH oxidase (NOX)2, NOX4, P22phox, and P47phox in ADM-induced cardiomyocytes. Mechanistically, HDPS-2II suppressed ADM-induced up-regulation of NOX2 and NOX4 in cardiomyocytes, but not in NOX2 or NOX4 knocked-down cardiomyocytes, indicating that HDPS-2II could relieve intracellular DNA damage by regulating NOX2/NOX4 signaling. These findings demonstrate that HDPS-2II is a new potential DNA protective agent.


Subject(s)
DNA Damage , Glycolipids , Animals , DNA Damage/drug effects , Glycolipids/pharmacology , Glycolipids/chemistry , Coleoptera , Reactive Oxygen Species/metabolism , Antioxidants/pharmacology , Antioxidants/chemistry , Cricetulus , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification
4.
Adv Sci (Weinh) ; 11(25): e2401583, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38659239

ABSTRACT

The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo-electron microscopy (cryo-EM) structures of human TRPV4 are presented in-complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage-sensing-like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small-molecule antagonists, which may facilitate future drug discovery targeting TRPV4.


Subject(s)
Cryoelectron Microscopy , TRPV Cation Channels , TRPV Cation Channels/antagonists & inhibitors , TRPV Cation Channels/metabolism , TRPV Cation Channels/chemistry , TRPV Cation Channels/genetics , Humans , Cryoelectron Microscopy/methods , Molecular Dynamics Simulation , Binding Sites
5.
Front Cell Neurosci ; 18: 1352630, 2024.
Article in English | MEDLINE | ID: mdl-38572075

ABSTRACT

Introduction: Spinal cord injury (SCI) is a severely disabling disease. Hyperactivation of neuroinflammation is one of the main pathophysiological features of secondary SCI, with phospholipid metabolism playing an important role in regulating inflammation. Phospholipase D (PLD), a critical lipid-signaling molecule, is known to be involved in various physiological processes, including the regulation of inflammation. Despite this knowledge, the specific role of PLD in SCI remains unclear. Methods: In this study, we constructed mouse models of SCI and administered PLD inhibitor (FIPI) treatment to investigate the efficacy of PLD. Additionally, transcriptome sequencing and protein microarray analysis of spinal cord tissues were conducted to further elucidate its mechanism of action. Results: The results showed that PLD expression increased after SCI, and inhibition of PLD significantly improved the locomotor ability, reduced glial scarring, and decreased the damage of spinal cord tissues in mice with SCI. Transcriptome sequencing analysis showed that inhibition of PLD altered gene expression in inflammation regulation. Subsequently, the protein microarray analysis of spinal cord tissues revealed variations in numerous inflammatory factors. Biosignature analysis pointed to an association with immunity, thus confirming the results obtained from transcriptome sequencing. Discussion: Collectively, these observations furnish compelling evidence supporting the anti-inflammatory effect of FIPI in the context of SCI, while also offering important insights into the PLD function which may be a potential therapeutic target for SCI.

6.
JACS Au ; 4(2): 619-634, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38425922

ABSTRACT

In the era of global climate change, the increasingly severe Fusarium head blight (FHB) and deoxynivalenol (DON) contamination have caused economic losses and brought food and feed safety concerns. Recently, an FHB resistance gene Fhb7 coding a glutathione-S transferase (GST) to degrade DON by opening the critical toxic epoxide moiety was identified and opened a new window for wheat breeding and DON detoxification. However, the poor stability of Fhb7 and the elusiveness of the catalytic mechanism hinder its practical application. Herein, we report the first structure of Fhb7 at 2.41 Å and reveal a unique catalytic mechanism of epoxide opening transformation in GST family proteins. Furthermore, variants V29P and M10 showed that 5.5-fold and 266.7-fold longer half-life time than wild-type, respectively, were identified. These variants offer broad substrate scope, and the engineered biosafe Bacillus subtilis overexpressing the variants shows excellent DON degradation performance, exhibiting potential at bacterium engineering to achieve DON detoxification in the feed and biomedicine industry. This work provides a profound mechanistic insight into the enzymatic activities of Fhb7 and paves the way for further utilizing Fhb7-related enzymes in crop breeding and DON detoxification by synthetic biology.

7.
Front Immunol ; 15: 1368203, 2024.
Article in English | MEDLINE | ID: mdl-38545108

ABSTRACT

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.


Subject(s)
Foam Cells , Spinal Cord Injuries , Humans , Foam Cells/pathology , Spinal Cord Injuries/metabolism , Macrophages/metabolism , Central Nervous System/metabolism
8.
Curr Issues Mol Biol ; 46(2): 1291-1307, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38392200

ABSTRACT

Changes in intracellular nicotinamide adenine dinucleotide (NAD+) levels have been observed in various disease states. A decrease in NAD+ levels has been noted following spinal cord injury (SCI). Nicotinamide riboside (NR) serves as the precursor of NAD+. Previous research has demonstrated the anti-inflammatory and apoptosis-reducing effects of NR supplements. However, it remains unclear whether NR exerts a similar role in mice after SCI. The objective of this study was to investigate the impact of NR on these changes in a mouse model of SCI. Four groups were considered: (1) non-SCI without NR (Sham), (2) non-SCI with NR (Sham +NR), (3) SCI without NR (SCI), and (4) SCI with NR (SCI + NR). Female C57BL/6J mice aged 6-8 weeks were intraperitoneally administered with 500 mg/kg/day NR for a duration of one week. The supplementation of NR resulted in a significant elevation of NAD+ levels in the spinal cord tissue of mice after SCI. In comparison to the SCI group, NR supplementation exhibited regulatory effects on the chemotaxis/recruitment of leukocytes, leading to reduced levels of inflammatory factors such as IL-1ß, TNF-α, and IL-22 in the injured area. Moreover, NR supplementation notably enhanced the survival of neurons and synapses within the injured area, ultimately resulting in improved motor functions after SCI. Therefore, our research findings demonstrated that NR supplementation had inhibitory effects on leukocyte chemotaxis, anti-inflammatory effects, and could significantly improve the immune micro-environment after SCI, thereby promoting neuronal survival and ultimately enhancing the recovery of motor functions after SCI. NR supplementation showed promise as a potential clinical treatment strategy for SCI.

9.
Sci Rep ; 14(1): 4356, 2024 02 22.
Article in English | MEDLINE | ID: mdl-38388732

ABSTRACT

While microbial biogeochemical activities such as those involving denitrification and sulfate reduction have been considered to play important roles in material cycling in various aquatic ecosystems, our current understanding of the microbial community in groundwater ecosystems is remarkably insufficient. To assess the groundwater in the Ryukyu limestone aquifer of Okinawa Island, which is located in the southernmost region of Japan, we performed metagenomic analysis on the microbial communities at the three sites and screened for functional genes associated with nitrogen metabolism. 16S rRNA amplicon analysis showed that bacteria accounted for 94-98% of the microbial communities, which included archaea at all three sites. The bacterial communities associated with nitrogen metabolism shifted by month at each site, indicating that this metabolism was accomplished by the bacterial community as a whole. Interestingly, site 3 contained much higher levels of the denitrification genes such as narG and napA than the other two sites. This site was thought to have undergone denitrification that was driven by high quantities of dissolved organic carbon (DOC). In contrast, site 2 was characterized by a high nitrate-nitrogen (NO3-N) content and a low amount of DOC, and this site yielded a moderate amount of denitrification genes. Site 1 showed markedly low amounts of all nitrogen metabolism genes. Overall, nitrogen metabolism in the Ryukyu limestone aquifer was found to change based on environmental factors.


Subject(s)
Groundwater , Microbiota , Calcium Carbonate/metabolism , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Bacteria , Groundwater/chemistry , Nitrogen/metabolism , Denitrification , Nitrates/metabolism
10.
Waste Manag ; 176: 1-10, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38246072

ABSTRACT

With continuous advancements in the zero-waste strategy in China, transportation of fresh municipal solid waste to landfills has ceased in most first-tier cities. Consequently, the production of landfill gas has sharply declined because the supply of organic matter has decreased, rendering power generation facilities idle. However, by incorporating liquefied kitchen and food waste (LKFW), sustainable methane production can be achieved while consuming organic wastewater. In this study, LKFW and water (as a control group) were periodically injected into high and low organic wastes, respectively. The biochemical characteristics of the resulting gas and leachate were analyzed. LKFW used in this research generated 19.5-37.6 L of methane per liter in the post-methane production phase, highlighting the effectiveness of LKFW injection in enhancing the methane-producing capacity of the system. The release of H2S was prominent during both the rapid and post-methane production phases, whereas that of NH3 was prominent in the post-methane production phase. As injection continued, the concentrations of chemical oxygen demand, 5-d biological oxygen demand, total organic carbon, ammonia nitrogen, total nitrogen, and oil in the output leachate decreased and eventually reached levels comparable to those in the water injection cases. After nine rounds of injections, the biologically degradable matter of the two LKFW-injected wastes decreased by 8.2 % and 15.1 %, respectively. This study sheds light on determining the organic load, controlling odor, and assessing the biochemical characteristics of leachate during LKFW injection.


Subject(s)
Refuse Disposal , Water Pollutants, Chemical , Solid Waste , Refuse Disposal/methods , Food Loss and Waste , Food , Bioreactors , Water Pollutants, Chemical/analysis , Waste Disposal Facilities , Methane/analysis , Water , Nitrogen
11.
Science ; 383(6683): 622-629, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38271490

ABSTRACT

Paclitaxel is a well known anticancer compound. Its biosynthesis involves the formation of a highly functionalized diterpenoid core skeleton (baccatin III) and the subsequent assembly of a phenylisoserinoyl side chain. Despite intensive investigation for half a century, the complete biosynthetic pathway of baccatin III remains unknown. In this work, we identified a bifunctional cytochrome P450 enzyme [taxane oxetanase 1 (TOT1)] in Taxus mairei that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, which represents a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible for the taxane oxidation of the C9 position (T9αH1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.


Subject(s)
Alkaloids , Cytochrome P-450 Enzyme System , Metabolic Engineering , Paclitaxel , Plant Proteins , Taxoids , Taxus , Alkaloids/biosynthesis , Alkaloids/genetics , Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/metabolism , Ethers, Cyclic/chemistry , Ethers, Cyclic/metabolism , Paclitaxel/biosynthesis , Taxoids/metabolism , Taxus/enzymology , Taxus/genetics , Cytochrome P-450 Enzyme System/chemistry , Cytochrome P-450 Enzyme System/genetics , Plant Proteins/chemistry , Plant Proteins/genetics
12.
Neuroscience ; 537: 93-104, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38056621

ABSTRACT

The inflammatory mechanism of intracerebral hemorrhage (ICH) has been widely studied, and it is believed that the regulation of this mechanism is of great significance to the prognosis. In the early stage of the acute phase of ICH, the release of a large number of inflammatory factors around the hematoma can recruit more inflammatory cells to infiltrate the area, further release inflammatory factors, cause an inflammatory cascade reaction, aggravate the volume of cerebral hematoma and edema and further destroy the blood-brain barrier (BBB), according to this, the crosstalk between cells may be of great significance in secondary brain injury (SBI). Because most of the cells recruited are inflammatory immune cells, this paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH, we found that among the main cells inherent in the brain, glial cells account for the majority, of which microglia are the most widely studied and it can interact with a variety of cells, which is reflected in the literature researches on its pathogenesis and treatment. We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend, and the existing research, the comparison and unification of modeling methods, and the observation of long-term efficacy may be the first problem that researchers need to solve.


Subject(s)
Brain , Cerebral Hemorrhage , Humans , Brain/pathology , Cerebral Hemorrhage/drug therapy , Blood-Brain Barrier/pathology , Inflammation/drug therapy , Hematoma/complications , Hematoma/drug therapy , Hematoma/pathology
13.
Sci Total Environ ; 912: 169457, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38135078

ABSTRACT

Denitrification crucially regulates the attenuation of groundwater nitrate and is unlikely to occur in a fast-flowing aquifer such as the Ryukyu limestone aquifer in southern Okinawa Island, Japan. However, evidences of denitrification have been observed in several wells within this region. This study analyzed environmental isotopes (δ15NNO3 and ẟ18ONO3) to derive the rationale for denitrification at this site. Additionally, the presence of two subsurface dams in the study area may influence the processes involved in nitrate attenuation. Herein, we analyzed 150 groundwater samples collected spatially and seasonally to characterize the variations in the groundwater chemistry and stable isotopes during denitrification. The values of δ15NNO3 and δ18ONO3 displayed a progressive trend up to +59.7 ‰ and + 21 ‰, respectively, whereas the concentrations of NO3--N decreased to 0.1 mg L-1. In several wells, the enrichment factors of δ15NNO3 ranged from -6.6 to -2.1, indicating rapid denitrification, and the δ15NNO3 to δ18ONO3 ratios varied from 1.3:1 to 2:1, confirming the occurrence of denitrification. Denitrification intensively proceeds under conditions of depleted dissolved oxygen concentrations (<2 mg L-1), sluggish groundwater flow with longer residence times, high concentrations of dissolved organic carbon (>1.2 mg L-1), and low groundwater levels during the dry season with precipitation rates of <100 mm per month (Jun-Sep). SF6 analysis indicated the exclusive occurrence of denitrification in specific wells with groundwater residence times exceeding 30 years. These wells are located in close proximity to the major NE-SW fault system in the Komesu area, where the hydraulic gradient was below 0.005. Detailed geological and lithological investigations based on borehole data revealed that subsurface dams did not cause denitrification while the major NE-SW fault system uplifted the impermeable basement rock of the Shimajiri Group, creating a lithological gap at an equivalent depth that ultimately formed a sluggish groundwater area, promoting denitrification.

14.
Technol Health Care ; 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-38073341

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an infiltrative malignancy characterized by a significantly elevated recurrence rate. Dickkopf-related protein 1 (DKK1), which plays an oncogene role in many cancers, acts as an inhibitor of the Wingless protein (Wnt) signaling pathway. Currently, there is a lack of consensus regarding the role of DKK1 in OSCC or its clinical significance. OBJECTIVE: To examine the role and effect of DKK1 in OSCC. METHODS: The identification of differentially expressed genes (DEGs) in OSCC was conducted by utilizing databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A comprehensive analysis of gene expression profile interactions (GEPIA) and Kaplan-Meier curve were conducted to investigate the associations among DEGs, patient survival and prognosis in individuals with OSCC. The biological function of DKK1 in OSCC was investigated by using molecular biology approaches. RESULTS: The expression of DKK1 was found to be upregulated in OSCC tissues at various stages. High levels of DKK1 expression exhibited a positive correlation with the overall survival (OS) and progression-free survival (PFS) rates among OSCC patients. DKK1 knockdown suppressed the proliferation and induced apoptotic response in OSCC cells. Moreover, DKK1 exerted a positive regulatory effect on HMGA2 expression, thereby modulating cell growth and apoptosis in OSCC. The expression of DKK1 was found to be positively correlated with the infiltration of immune cells in patients with OSCC. Additionally, higher levels of CD4+ T cells were associated with improved 5-year survival rates. CONCLUSION: DKK1 is a prognostic biomarker for patients with OSCC.

15.
World J Clin Cases ; 11(35): 8431-8433, 2023 Dec 16.
Article in English | MEDLINE | ID: mdl-38130605

ABSTRACT

This article enthusiastically explores the study of highly aggressive variant prostate cancer (AVPC), acknowledging its relatively rare yet highly menacing presence within the realm of prostate cancer. The paper delves into the pathological characteristics of AVPC, diagnostic and therapeutic challenges, and the potential applications of precision medicine and molecular imaging in the future.

16.
Front Cell Neurosci ; 17: 1323566, 2023.
Article in English | MEDLINE | ID: mdl-38155866

ABSTRACT

Background: Nicotinamide mononucleotide (NMN), an important transforming precursor of nicotinamide adenine dinucleotide (NAD+). Numerous studies have confirmed the neuroprotective effects of NMN in nervous system diseases. However, its role in spinal cord injury (SCI) and the molecular mechanisms involved have yet to be fully elucidated. Methods: We established a moderate-to-severe model of SCI by contusion (70 kdyn) using a spinal cord impactor. The drug was administered immediately after surgery, and mice were intraperitoneally injected with either NMN (500 mg NMN/kg body weight per day) or an equivalent volume of saline for seven days. The central area of the spinal cord was harvested seven days after injury for the systematic analysis of global gene expression by RNA Sequencing (RNA-seq) and finally validated using qRT-PCR. Results: NMN supplementation restored NAD+ levels after SCI, promoted motor function recovery, and alleviated pain. This could potentially be associated with alterations in NAD+ dependent enzyme levels. RNA sequencing (RNA-seq) revealed that NMN can inhibit inflammation and potentially regulate signaling pathways, including interleukin-17 (IL-17), tumor necrosis factor (TNF), toll-like receptor, nod-like receptor, and chemokine signaling pathways. In addition, the construction of a protein-protein interaction (PPI) network and the screening of core genes showed that interleukin 1ß (IL-1ß), interferon regulatory factor 7 (IRF 7), C-X-C motif chemokine ligand 10 (Cxcl10), and other inflammationrelated factors, changed significantly after NMN treatment. qRT-PCR confirmed the inhibitory effect of NMN on inflammatory factors (IL-1ß, TNF-α, IL-17A, IRF7) and chemokines (chemokine ligand 3, Cxcl10) in mice following SCI. Conclusion: The reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model. RNA-seq and qRT-PCR systematically revealed that NMN affected inflammation-related signaling pathways, including the IL-17, TNF, Toll-like receptor, NOD-like receptor and chemokine signaling pathways, by down-regulating the expression of inflammatory factors and chemokines.

17.
Inflammation ; 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37975960

ABSTRACT

Oxidative stress is a frequently occurring pathophysiological feature of spinal cord injury (SCI) and can result in secondary injury to the spinal cord and skeletal muscle atrophy. Studies have reported that glycine and N-acetylcysteine (GlyNAC) have anti-aging and anti-oxidative stress properties; however, to date, no study has assessed the effect of GlyNAC in the treatment of SCI. In the present work, we established a rat model of SCI and then administered GlyNAC to the animals by gavage at a dose of 200 mg/kg for four consecutive weeks. The BBB scores of the rats were significantly elevated from the first to the eighth week after GlyNAC intervention, suggesting that GlyNAC promoted the recovery of motor function; it also promoted the significant recovery of body weight of the rats. Meanwhile, the 4-week heat pain results also suggested that GlyNAC intervention could promote the recovery of sensory function in rats to some extent. Additionally, after 4 weeks, the levels of glutathione and superoxide dismutase in spinal cord tissues were significantly elevated, whereas that of malondialdehyde was significantly decreased in GlyNAC-treated animals. The gastrocnemius wet weight ratio and total antioxidant capacity were also significantly increased. After 8 weeks, the malondialdehyde level had decreased significantly in spinal cord tissue, while reactive oxygen species accumulation in skeletal muscle had decreased. These findings suggested that GlyNAC can protect spinal cord tissue, delay skeletal muscle atrophy, and promote functional recovery in rats after SCI.

18.
Waste Manag ; 171: 557-567, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37806163

ABSTRACT

The complex process of thermal-hydro-mechanical-biochemical (THMBC) coupled degradation in high food waste content (HFWC) municipal solid waste (MSW) is the main cause of intense heat, gas, and leachate generation in the landfills, which could lead to environmental disasters. A large-scale indoor experiment on HFWC MSW has been done with operations of loading, heated mature leachate recharging to study the rules of degradation. A THMBC coupled degradation model is used to analyze the results in the first 400 days drawn from the experiments, to explain how recharge of heated mature leachate accelerated degradation process and how was the portion of settlement led by intraparticle water release. The numerical simulation also calculated the landfill gas that was not collected in the experiment due to operational defects. The results show that recharging the heated mature leachate allows the stabilization process to occur at least six months earlier and settlement due to intraparticle water release accounts for half of the settlement in the first 60 days. The research indicates highly coupled THMBC model can be used to analyze the complex process in MSW degradation, make up for the shortcomings of physical experiments, and provide theoretical support for the design, construction, and management of landfills.

19.
Org Lett ; 25(36): 6784-6789, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37672351

ABSTRACT

Herein, we present a base-mediated nucleophilic substitution reaction of α-trifluoromethylstyrenes with simple silyl enol ethers, enabling the efficient synthesis of carbonyl-substituted gem-difluoroalkenes. The merit of this protocol is exhibited by its mild reaction conditions, broad substrate scope, and scalable preparation. Notably, this method demonstrates its applicability for late-stage functionalization of structurally complex molecules. Moreover, we illustrate that the resulting products can serve as valuable precursors for the synthesis of diverse medicinally relevant compounds.

20.
Int J Biol Macromol ; 250: 126133, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37543263

ABSTRACT

Hydrogels have been demonstrated as smart drug carriers to recognize the tumor microenvironment for cancer treatment, where the dynamic crosslinks in the hydrogel network contribute to the stimuli-responsive features but also result in poor stability and weak mechanical property of the hydrogels. Here, phenylboronic acid-grafted polyethyleneimine (PBA-PEI)-modified gelatin (PPG) was synthesized to crosslink alginate dialdehyde (ADA) through imine bonds and boronate ester bonds, and then calcium ions (Ca2+) were added to introduce the third calcium-carboxylate crosslinking in the network to form the triple-crosslinked PPG/ADA-Ca2+ hydrogels. Given the three types of dynamic bonds in the network, PPG/ADA-Ca2+ hydrogels possessed a self-healing manner, stimuli-responsiveness, and better mechanical properties compared to single- or double-crosslinked hydrogels. The controlled release capability of PPG/ADA-Ca2+ hydrogels was also demonstrated, showing the encapsulated molecules can be rapidly released from the hydrogel network in the presence of hydrogen peroxide while the release rate can be slowed down at acidic pH. Furthermore, PPG/ADA-Ca2+ hydrogels presented selected cytotoxicity and drug delivery to cancer cells due to the regulated degradation by the cellular microenvironment. Taken together, PPG/ADA-Ca2+ hydrogels have been demonstrated as promising biomaterials with multiple desirable properties and dynamic features to perform controlled molecule release for biomedical applications.

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