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1.
World J Clin Cases ; 12(26): 5983-5989, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39286392

ABSTRACT

BACKGROUND: A sclerosing epithelioid fibrosarcoma (SEF) is a rare malignant fibroblastic soft tissue tumor that rarely occurs in intra-abdominal organs. A case of a SEF in the pancreatic head is reported herein, including its clinical manifestations, preoperative imaging features, gross specimen and pathological findings. CASE SUMMARY: A 33-year-old male patient was admitted to Peking Union Medical College Hospital in December 2023 due to a one-year history of intermittent upper abdominal pain and the discovery of a pancreatic mass. The patient underwent an enhanced computed tomography scan of the abdomen, which revealed a well-defined, round mass with clear borders and calcifications in the pancreatic head. The mass exhibited progressive, uneven mild enhancement, measuring approximately 6.6 cm × 6.3 cm. The patient underwent laparoscopic pylorus-preserving pancreaticoduodenectomy. Postoperative pathological examination revealed that the lesion was consistent with a SEF. At the 3-month postoperative follow-up, the patient did not report any short-term complications, and there were no signs of tumor recurrence. CONCLUSION: SEFs are rare malignant fibrous soft tissue tumors. SEFs rarely develop in the pancreas, and its preoperative diagnosis depends on imaging findings, with confirmation depending on pathological examination and immunohistochemistry. Currently, only four cases of pancreatic SEF have been reported in studies written in English. This case is the first reported case of a pancreatic SEF by a clinical physician.

2.
Cell Mol Life Sci ; 81(1): 402, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39276234

ABSTRACT

The excessive inflammation caused by the prolonged activation of Toll-like receptor 4 (TLR4) and its downstream signaling pathways leads to sepsis. CD14-mediated endocytosis of TLR4 is the key step to control the amount of TLR4 on cell membrane and the activity of downstream pathways. The actin cytoskeleton is necessary for receptor-mediated endocytosis, but its role in TLR4 endocytosis remains elusive. Here we show that Tropomodulin 1 (Tmod1), an actin capping protein, inhibited lipopolysaccharide (LPS)-induced TLR4 endocytosis and intracellular trafficking in macrophages. Thus it resulted in increased surface TLR4 and the upregulation of myeloid differentiation factor 88 (MyD88)-dependent pathway and the downregulation of TIR domain-containing adaptor-inducing interferon-ß (TRIF)-dependent pathway, leading to the enhanced secretion of inflammatory cytokines, such as TNF-α and IL-6, and the reduced secretion of cytokines, such as IFN-ß. Macrophages deficient with Tmod1 relieved the inflammatory response in LPS-induced acute lung injury mouse model. Mechanistically, Tmod1 negatively regulated LPS-induced TLR4 endocytosis and inflammatory response through modulating the activity of CD14/Syk/PLCγ2/IP3/Ca2+ signaling pathway, the reorganization of actin cytoskeleton, and the membrane tension. Therefore, Tmod1 is a key regulator of inflammatory response and immune functions in macrophages and may be a potential target for the treatment of excessive inflammation and sepsis.


Subject(s)
Endocytosis , Inflammation , Lipopolysaccharides , Macrophages , Mice, Inbred C57BL , Signal Transduction , Toll-Like Receptor 4 , Tropomodulin , Animals , Humans , Mice , Actin Cytoskeleton/metabolism , Acute Lung Injury/metabolism , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Adaptor Proteins, Vesicular Transport/metabolism , Adaptor Proteins, Vesicular Transport/genetics , Cytokines/metabolism , Inflammation/metabolism , Inflammation/pathology , Lipopolysaccharide Receptors/metabolism , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Macrophages/immunology , Mice, Knockout , Myeloid Differentiation Factor 88/metabolism , Myeloid Differentiation Factor 88/genetics , RAW 264.7 Cells , Toll-Like Receptor 4/metabolism , Tropomodulin/metabolism , Tropomodulin/genetics
3.
J Med Microbiol ; 73(8)2024 Aug.
Article in English | MEDLINE | ID: mdl-39213028

ABSTRACT

Introduction. Hypertension is the most prevalent chronic disease and a major risk factor for cardiovascular and cerebrovascular diseases.Gap statement. However, there has been no substantial breakthrough in aetiology, new drug targets, and drug development of hypertension in recent 50 years.Research aim. Therefore, this study was to screen unique intestinal microbiome and serum metabolic biomarkers which can early diagnose and track the prognosis of hypertension patients in different periods, and analyse its underlying mechanisms and functions.Methods. Four groups of stool and serum samples, including healthy controls (HCs), prehypertension (PHT), hypertension (HT), and hypertension-related complications (HTC), were collected. Microbial diversity assessed using 16S rRNA sequencing. The metabolites in serum samples were detected through LC-MS/MS analysis.Results. The composition of gut microbiota in patients exhibited dissimilarities compared to that in healthy subjects, which was distinguished by Prevotella, Slackia, Enterococcus, Bifidobacterium, and Lactobacillales may be potential markers for tracking the progression of hypertension, and Bifidobacterium, Butyricimonas, Adlercreutzia, Faecalibacterium, Lactobacillus, Ruminococcus, Clostridium, and Acidaminococcus demonstrated diagnostic value. Meanwhile, tracking the dynamic changes of deoxycholic acid, 4-oxododecanedioic acid, and l-arginine can serve as biomarkers for early diagnosis, and investigation into the mechanism by which the intestinal microbiome influences the onset and progression of hypertension. In terms of pathogenesis, the findings revealed that Bifidobacterium may caused the changes of AST, indirect bilirubin, ALT, triglyceride and uric acid by affecting metabolites cis-7-hexadecenoic acid methyl ester and N1-acetylspermidine. Additionally, Coprococcus may cause changes in albumin through the influence of androsterone enanthate.Conclusions. These findings highlight that the unique intestinal microbiome and serum metabolic profile in different periods of hypertension will provide valuable insight for timely diagnosis and prognosis tracking in hypertension patients with promising clinical applications.


Subject(s)
Biomarkers , Early Diagnosis , Feces , Gastrointestinal Microbiome , Hypertension , Metabolome , Humans , Biomarkers/blood , Hypertension/microbiology , Hypertension/diagnosis , Middle Aged , Prognosis , Male , Female , Feces/microbiology , Adult , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Bacteria/metabolism , Aged , Tandem Mass Spectrometry , Case-Control Studies
4.
Org Lett ; 26(35): 7442-7446, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39186378

ABSTRACT

A visible light-promoted aromatization-driven deconstructive fluorination of spiro carbocycles is presented. A series of spiro dihydroquinazolinones reacted efficiently with NFSI under visible light irradiation to afford the 2-(4-fluoroalkyl)quinazolin-4(3H)-ones in good yields with excellent functional group tolerance. A radical pathway involving C-C bond cleavage and F atom transfer is proposed for the reaction. In addition, the ring-opening chlorination of spiro dihydroquinazolinones with NCS was also applicable.

5.
Free Radic Biol Med ; 223: 306-324, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39134162

ABSTRACT

The systemic inflammatory response syndrome (SIRS) represents a self-amplifying cascade of inflammatory reactions and pathophysiological states triggered by infectious or non-infectious factors. The identification of disease targets and differential proteins in the liver (the unique and important immune organ) of SIRS mice treated with the lead compound D1 was conducted using the Genecards database and proteomic analysis, respectively. Subsequently, NOTCH1 was identified as the potential hub target via an intersection analysis between the aforementioned differentially expressed proteins and disease targets. Based on our previous research on the structure-activity relationship, we designed and synthesized a series of SIRS-related derivatives, wherein butyl, halogen, and ester groups were incorporated into benzophenone, aiming at exploring the anti-inflammatory protective action from the perspective of macrophage polarization. Notably, these derivatives exhibited a direct binding capability to the O-glucosylation site (SER496) or its vicinities (such as SER492, VAL485) of NOTCH1 using docking, SPR, DARTS, and CETSA techniques. Mechanistically, derivative D6 exerted anti-inflammatory effects via the dual NOTCH pathway. Firstly, it could inhibit NOTCH1 nuclear transcriptional activity, attenuate the interaction between NICD and RBPJK, concurrently suppress NF-κB and NLRP3 inflammasome (NLRP3, ASC, and cleaved CASP1) activation, and promote NICD (NOTCH1 active fragments) ubiquitination metabolism (the nuclear transcriptional pathway). Secondly, it might possess the ability to increase PGC1α level, subsequently, enhance ATP and MMP levels, mitigate ROS production, increase mitochondrial numbers, and ameliorate mitochondrial inflammatory damage (the mitochondrial pathway). Importantly, the activator Jagged1 could effectively reverse the aforementioned effects, while the inhibitor DAPT exhibited a synergistic effect, suggesting that the nuclear transcriptional regulation and mitochondrial regulation were both in a NOTCH1-dependent manner. Subsequently, it effectively alleviated the inflammatory response and preserved organ function as evidenced by up-regulating M2-type macrophage-related anti-inflammatory cytokines (IL10, TGFß, CD206, and ARG1) and down-regulating M1-type macrophage-related pro-inflammatory cytokines (NO, IL6, IL18, iNOS, TNFα, CD86, and IL1ß). In a word, derivative D6 modulated macrophage polarization and effectively mitigated SIRS by targeting inhibition of the dual NOTCH pathway.


Subject(s)
Benzophenones , Mitochondria , Receptor, Notch1 , Signal Transduction , Systemic Inflammatory Response Syndrome , Animals , Benzophenones/pharmacology , Benzophenones/chemistry , Mice , Receptor, Notch1/metabolism , Receptor, Notch1/genetics , Signal Transduction/drug effects , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/pathology , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/pathology , Macrophages/drug effects , Macrophages/metabolism , Macrophages/pathology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Humans , Male , Molecular Docking Simulation , Inflammasomes/metabolism , Inflammasomes/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Disease Models, Animal , RAW 264.7 Cells , Transcription, Genetic/drug effects , Structure-Activity Relationship
6.
Chemistry ; : e202402602, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112402

ABSTRACT

Mild and inexpensive copper-catalyzed aromatization-driven ring-opening amination and oxygenation of spiro dihydroquinazolinones are presented, respectively. These protocols provide facile and atom-economical access to the aminated and the carbonyl-containing quinazolin-4(3H)-ones in good yields with good functional group compatibility, which are difficult to obtain by conventional methods. Remarkably, a telescoped procedure involving the condensation and the ring-opening/functionalization for simple cycloalkanone was found to be accessible. Mechanistic studies suggest a radical pathway for this transformation.

7.
Int J Med Mushrooms ; 26(9): 65-76, 2024.
Article in English | MEDLINE | ID: mdl-39093402

ABSTRACT

To study and compare the morphology of the phellinoid Agaricomycetes strains and find other strategies to improve Phellinus spp. growth and metabolism. In this study, the morphological characteristics of four Phellinus igniarius strains (phellinoid Agaricomycetes) were observed under a light microscope. The exudates from these fungi were observed using light microscopy, scanning electron microscopy (SEM), and energy-dispersive spectrometry (EDS). The exudates were initially transparent with a water-like appearance, and became darker with time at neutral pH. Microscopy of air-dried exudates revealed regular shapes and crystals. Cl- (chloride) and K+ were the two key elements analyzed using EDS. Polyphenol oxidase (POD), catalase (CAT), and laccase activities were detected in mycelia from each of the four Phellinus strains. The K+ content of the three strains was higher than that of the wild strain. Cl- content correlated negatively with that of K+. Laccase activities associated with each mycelia and its corresponding media differed under cold and contaminated conditions.


Subject(s)
Basidiomycota , Laccase , Microscopy, Electron, Scanning , Mycelium , Laccase/metabolism , Basidiomycota/enzymology , Basidiomycota/chemistry , Mycelium/chemistry , Catalase/metabolism , Catechol Oxidase/metabolism , Potassium/metabolism , Chlorides/metabolism
8.
Int J Biol Macromol ; 277(Pt 2): 134155, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39098462

ABSTRACT

N-doped TiO2/carbon composites (N-TiPC) have shown excellent photodegradation performances to the organic contaminants but are limited by the multistage preparation (i.e., preparation of porous carbon, preparation of N-doped TiO2, and loading of N-doped TiO2 on porous carbon). Here, we develop a handy way by combining the Pickering emulsion-gel template route and chelation reaction of polysaccharides. The N-TiPC is obtained by calcinating pectin/Dl-serine hydrazide hydrochloride (SHH)-Ti4+ chelate and is further described by modern characterization techniques. The results show that the N atom is successfully doped into the TiO2 lattice, and the bandgap value of N-TiPC is reduced to 2.3 eV. Moreover, the particle size of N-TiPC remains about 10 nm. The configurations of the composites are simulated using DFT calculation. The photocatalytic experiments show that N-TiPC has a high removal efficiency for methylene blue (MB) and oxytetracycline hydrochloride (OTC-HCL). The removal ratios of MB (20 mg/L, 50 mL) and OTC-HCL (30 mg/L, 50 mL) are 99.41 % and 78.29 %, respectively. The cyclic experiments show that the photocatalyst has good stability. Overall, this study provides a handy way to form N-TiPC with enhanced photodegradation performances. It can also be promoted to other macromolecules such as cellulose and its derivatives, sodium alginate, chitosan, lignin, etc.


Subject(s)
Carbon , Pectins , Serine , Titanium , Pectins/chemistry , Titanium/chemistry , Carbon/chemistry , Serine/chemistry , Nitrogen/chemistry , Catalysis , Photolysis , Porosity , Methylene Blue/chemistry
9.
R Soc Open Sci ; 11(6): 231979, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39092147

ABSTRACT

Macrocyclic polyamines constitute a significant class of macrocyclic compounds that play a pivotal role in the realm of supramolecular chemistry. They find extensive applications across diverse domains including industrial and agricultural production, clinical diagnostics, environmental protection and other multidisciplinary fields. Macrocyclic polyamines possess a distinctive cavity structure with varying sizes, depths, electron-richness degrees and flexibilities. This unique feature enables them to form specific supramolecular structures through complexation with diverse objects, thereby attracting considerable attention from chemists, biologists and materials scientists alike. However, there is currently a lack of comprehensive summaries on the synthesis methods for macrocyclic polyamines. In this review article, we provide an in-depth introduction to the synthesis of macrocyclic polyamines while analysing their respective advantages and disadvantages. Furthermore, we also present an overview of the recent 5-year advancements in using macrocyclic polyamines as non-viral gene vectors, fluorescent probes, diagnostic and therapeutic reagents as well as catalysts. Looking ahead to future research directions on the synthesis and application of macrocyclic polyamines across various fields will hopefully inspire new ideas for their synthesis and use.

10.
Meat Sci ; 217: 109606, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39033556

ABSTRACT

This study aims to evaluate the pork meat quality after ultrasonic brining at different frequencies, thereby providing a more comprehensive understanding of the effects of ultrasound marination on meat. The texture profile analysis showed that ultrasonic curing at various frequencies significantly improved the textural properties of samples, especially at 26.8 kHz, resulting in a reduction of tenderness, hardness, and chewiness values by 44%, 43%, and 44%, respectively. The cooking loss of samples marinated by ultrasound decreased from 27% without ultrasonic treatment to 22%, indicating a significant improvement in water-holding capacity, while the changes in pH had only a subtle impact on pork quality. Meanwhile, the color of pork became more rosy hue due to decreased L⁎ values and increased a⁎ values, which was mainly attributed to an elevated proportion of oxymyoglobin and reduced metmyoglobin content. Additionally, ultrasonic marination did not exert a negative impact on the oxidation of pork protein and lipids. After roasting, samples marinated by ultrasound exhibited a significantly higher abundance of volatile flavor compounds compared to static marinated meat (with an increase of 16 flavor substances) and fresh pork (with an increase of 24 flavor substances), demonstrating the efficacy of ultrasonic marination in enhancing the overall flavor and taste profile of pork. Consequently, the application of ultrasonic technology holds great potential for the "home kitchen type" rapid marination.


Subject(s)
Cooking , Food Handling , Myoglobin , Pork Meat , Volatile Organic Compounds , Animals , Myoglobin/analysis , Pork Meat/analysis , Volatile Organic Compounds/analysis , Swine , Cooking/methods , Food Handling/methods , Taste , Color , Cold Temperature
11.
Chem Commun (Camb) ; 60(62): 8095-8098, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38993023

ABSTRACT

Metal-free, photoredox-catalyzed aromatization-driven deconstructive functionalization of spiro-dihydroquinazolinones with α-CF3 alkenes is presented. The readily available spiro-dihydroquinazolinones reacted efficiently with α-CF3 alkenes during photocatalysis to give the gem-difluoroallylated and the CF3-containing quinazolin-4(3H)-ones in good yields with excellent chemoselectivity. The selectivity depends on the electron effect of substituents in α-CF3 alkenes. A wide range of four-, five-, six-, seven-, eight- and twelve-membered spiro-dihydroquinazolinones were compatible with this transformation. The protocol is also characterized by the mild and redox-neutral reaction conditions, good functional group compatibility and excellent atom economy. Mechanistic studies revealed that the reaction proceeds via a radical pathway.

12.
Glycoconj J ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046578

ABSTRACT

Pertussis vaccines have been very effective in controlling whooping-cough epidemics but are ineffective in controlling circulation in older children and adults, thus facilitating the onset of future outbreaks. Antibodies against the lipopolysaccharide could reduce the carriage of the bacteria, its circulation, and transmission. The oligosaccharide fragments from the lipopolysaccharide may become a potential complement to existing vaccines in the form of protein glycoconjugates. An important step in the development of this type of vaccine is defining the minimal oligosaccharide epitope recognized by B. pertussis anti-lipopolysaccharide antibodies. This paper describes the complete synthesis of oligosaccharides containing two to five monosaccharide units corresponding to the pentasaccharide at the nonreducing end of the lipooligosaccharide and their recognition by mice and rabbit antibodies elicited against whole-cell B. pertussis. For the first time, we report that the terminal disaccharide, α-D-GlcNAcp-(1 → 4)-(2,3-di-NAc)-D-ManAp acid is the minimal structure recognized by antibodies induced by B. pertussis.

13.
BMC Psychiatry ; 24(1): 517, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039478

ABSTRACT

BACKGROUND: Depression and anxiety symptoms among medical students are often a concern. The Patient Health Questionnaire-Four (PHQ-4), an important tool for depression and anxiety screening, is commonly used and easy to administer. This study aimed to assess and update the longitudinal measurement invariance and psychometric properties of the simplified Chinese version. METHODS: A three-wave longitudinal survey was conducted among healthcare students using the PHQ-4. Structural validity was based on one-factor, two-factor, and second-order factor models, construct validity was based on the Self-Rated Health Questionnaire (SRHQ), Sleep Quality Questionnaire (SQQ), and Rosenberg Self-Esteem Scale (RSES), and longitudinal measurement invariance (LMI), internal consistency, and test-retest reliability were based on structural consistency across three time points. RESULTS: The results of the confirmatory factor analysis indicated that two-factor model was the best fit, and LMI was supported at three time points. Inter-factor, factor-total, and construct validity correlations of the PHQ-4 were acceptable. Additionally, Cronbach's alpha, McDonald's omega, and the intraclass correlation coefficient demonstrated acceptable/moderate to excellent reliability of the PHQ-4. CONCLUSIONS: This study adds new longitudinal evidence that the Chinese version of the PHQ-4 has promising LMI and psychometric properties. Such data lends confidence to the routine and the expanded use of the PHQ-4 for routine screening of depression and anxiety in Chinese healthcare students.


Subject(s)
Anxiety , Depression , Patient Health Questionnaire , Psychometrics , Humans , China , Female , Male , Longitudinal Studies , Reproducibility of Results , Depression/psychology , Depression/diagnosis , Anxiety/psychology , Anxiety/diagnosis , Adult , Young Adult , Students, Medical/psychology , Factor Analysis, Statistical , Surveys and Questionnaires/standards
14.
Nutr Diabetes ; 14(1): 48, 2024 06 29.
Article in English | MEDLINE | ID: mdl-38951151

ABSTRACT

BACKGROUND: This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. METHODS: This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. RESULTS: Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. CONCLUSION: Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.


Subject(s)
Diabetes, Gestational , Genotype , Haptoglobins , Hemoglobins , Pregnancy Trimester, First , Humans , Female , Pregnancy , Diabetes, Gestational/genetics , Diabetes, Gestational/blood , Diabetes, Gestational/epidemiology , Haptoglobins/genetics , Retrospective Studies , Adult , Hemoglobins/analysis , China/epidemiology , Risk Factors , Asian People/genetics , Glycated Hemoglobin/analysis , Blood Glucose/analysis , Blood Glucose/metabolism , Insulin Resistance/genetics , East Asian People
15.
Insects ; 15(7)2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39057287

ABSTRACT

Smoothened (Smo) is a critical component regulating the Hedgehog signaling pathway. However, whether Smo is associated with the modulation of olfactory recognition capabilities of bees remains unclear. In this study, we amplified Smo from Apis mellifera. The coding sequence of Smo was 2952 bp long, encoded 983 amino acids. Smo was most highly expressed in the antennae. Cyclopamine (200 µg/mL) significantly reduced but purmorphamine (800 µg/mL) significantly increased Smo expression (p < 0.05). OR152 and OR2 expression in the cyclopamine group significantly decreased, whereas OR152 expression in the purmorphamine group significantly increased (p < 0.05). A significant decrease in the relative values of electroantennography was observed in the cyclopamine group exposed to neral. Behavioral tests indicated a significant decrease in the attractive rates of neral, VUAA1, linalool, and methyl heptenone in the cyclopamine group. Conversely, the selection rates of linalool and methyl heptenone in the purmorphamine group significantly increased. Our findings indicate that Smo may play a role in modulating olfactory receptors in bees.

16.
Bioorg Chem ; 150: 107612, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38986418

ABSTRACT

The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson's disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood-brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC50 = 70.44 ± 22.69 µM, diphenolase IC50 = 1.89 ± 0.64 µM), through the structure-based screening method. The compound 2-06 presented good in vitro and in vivo safety, and can inhibit the tyrosinase and melanogenesis in B16F10. Moreover, this compound showed neuroprotective effects and Parkinsonism behavior improving function. 2-06 was proved to penetrate the BBB and enter the central nervous system (CNS). The exploration of the binding mode between 2-06 and tyrosinase provided the foundation for the subsequent structural optimization. This is the first research to develop a central-targeting tyrosinase inhibitor, which is crucial for in-depth study on the new strategy for utilizing tyrosinase inhibitors to treat PD.


Subject(s)
Dose-Response Relationship, Drug , Drug Discovery , Enzyme Inhibitors , Monophenol Monooxygenase , Parkinson Disease , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Animals , Structure-Activity Relationship , Mice , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Molecular Structure , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemical synthesis , Humans , Male , Molecular Docking Simulation , Blood-Brain Barrier/metabolism
17.
Org Lett ; 26(28): 6030-6034, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38976347

ABSTRACT

A photoredox-catalyzed sequential decarboxylative/defluorinative aminoalkylation of CF3-alkenes with N-arylglycines is described. This metal-free and redox-neutral protocol provided efficient access to the monofluoroalkenyl-1,5-diamines in good yields with excellent functional group compatibility. Mechanistic studies revealed that the reaction proceeds via a radical pathway with the gem-difluoroalkenyl amine as an intermediate.

18.
Front Psychiatry ; 15: 1402680, 2024.
Article in English | MEDLINE | ID: mdl-39077626

ABSTRACT

Background: Anxiety, depression, and sleep problems are prevalent comorbid mental disorders among university students. The World Health Organization (WHO) emphasized a mental health promotion objective, recommending the consideration of protective health-promoting factors in strategies aimed at preventing mental disorders. Integrating theoretically significant constructs (such as protective factors) enhances our comprehension of the intricate mechanisms that underpin mental disorders. This study employed network analysis to first identify core and bridge symptoms within comorbid mental disorders and then explore how health-promoting lifestyles (HPLs) were associated with these disorders. The ultimate goal is to offer health promotion recommendations to enhance students' quality of life. Methods: A total of 3,896 qualified university students participated in this study. Anxiety, depression, sleep problems, and HPLs were assessed using the GAD-7, PHQ-9, PSQI, and HPLP-II scales. A Gaussian Graphical Model was used to construct the networks. The Network Comparison Test was applied to determine whether the associations between HPLs and comorbid symptoms vary by gender, educational level, family sibling, and mental health status. Results: Low energy (PHQ4) had the highest strength centrality, followed by Daytime dysfunction (PSQI7) and Trouble relaxing (GAD4). Five bridge symptoms were identified: Daytime dysfunction (PSQI7), Self-harm even suicide (PHQ9), Sad mood (PHQ2), Low energy (PHQ4), and Feeling afraid (GAD7). Regarding protective HPLs, Physical activity, Spiritual growth, and Stress management generally emerged as the top three central mental health-promoting behaviors. Conclusion: Targeting core and bridge symptoms with timely and appropriate interventions can alleviate anxiety, depression, and sleep problems in this population. Moreover, promoting physical activity, fostering spiritual growth, and managing stress are likely to significantly enhance the overall mental health of university students.

19.
Asian J Androl ; 26(5): 490-499, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38856299

ABSTRACT

ABSTRACT: Male infertility is a global issue caused by poor sperm quality, particularly motility. Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology (ART) treatment. Scriptaid, with a novel human sperm motility-stimulating activity, has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART. We evaluated the effects of Scriptaid on asthenozoospermic (AZS) semen, including its impact on motility stimulation and protective effects on cryopreservation and duration of motility, by computer-aided sperm analysis (CASA). Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity, tyrosine phosphorylation, adenosine triphosphate (ATP) concentration, mitochondrial membrane potential, and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection (ICSI) experiments. Furthermore, our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function. In summary, Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality, prolongs sperm viability, and increases the fertilization rate.


Subject(s)
Asthenozoospermia , Fertilization in Vitro , Sperm Motility , Spermatozoa , Humans , Male , Asthenozoospermia/drug therapy , Sperm Motility/drug effects , Spermatozoa/drug effects , Fertilization in Vitro/methods , Semen Analysis , Sperm Injections, Intracytoplasmic/methods , Female , Membrane Potential, Mitochondrial/drug effects , Cryopreservation/methods , Adenosine Triphosphate/metabolism , Adult
20.
Int J Nurs Pract ; : e13278, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862421

ABSTRACT

BACKGROUND: Illness perceptions are an important factor affecting the prognosis of stroke patients. Evaluating the illness perceptions of stroke patients is of great importance for predicting their health behaviour and rehabilitation outcomes. However, there is no specific tool for assessing illness perceptions in stroke patients in China. OBJECTIVES: The objective of this study is to translate the Stroke Illness Perception Questionnaire-Revised (SIPQ-R) into Chinese and to psychometrically test the Chinese version of the scale in the population of Chinese stroke patients. METHODS: This was a methodological study. We investigated 593 stroke patients in the neurology department of a hospital in China from March to September 2021. We translated the SIPQ-R and adapted it to the cultural context, after which we evaluated the reliability and validity of the Chinese version of SIPQ-R. RESULTS: Exploratory factor analysis identified eight common factors that accounted for 71.74% of the total variance, and the factor loadings ranged from 0.530 to 0.933. Confirmatory factor analysis confirmed the eight-factor structure (χ2/df = 1.765, root mean square error of approximation = 0.053, incremental fit index = 0.906, comparative fit index = 0.905 and Tucker-Lewis index = 0.900). Internal consistency was confirmed by a Cronbach's alpha coefficient of 0.982. The test-retest reliability was 0.762. The results showed good content validity (the scale level content validity index was 0.940, and the item level content validity index values ranged from 0.860 to 0.960). There were no missing responses and floor or ceiling effects. The standard error of measurement and the smallest detectable change for the SIPQ-R were 45.49 and 126.10, respectively. CONCLUSIONS: The results of this study provide empirical evidence for the reliability and validity of the Chinese version of the SIPQ-R for stroke patients.

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