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1.
Chin J Integr Med ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046647

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of Sanjie Analgesic Capsule (SAC) in Chinese patients with endometriosis-associated pain. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 centers between November 2013 and July 2017 in China. Eligible 323 patients with endometriosis were randomized at a 3:1 ratio to the SAC group (241 cases) and placebo group (82 cases) by stratified block randomization. Patients in the SAC or placebo groups were given SAC or placebo 1.6 g 3 times per day, orally, respectively since the first day of menstruation for 3 consecutive menstrual cycles. The primary endpoint was clinical response to dysmenorrhea evaluated using a 10-point Visual Analogue Scale at 3 and 6 months. The secondary endpoint was the pain score evaluated by VAS (chronic pelvic pain, defecation pain, and dyspareunia) at 3 and 6 months, and the pain recurrence rate at 6 months. Adverse events (AEs) were recorded during the study. RESULTS: A total of 241 women were included in the SAC group, and 82 were in the placebo group. Among these women, 217 (90.0%) and 71 (86.6%) completed the intervention, respectively. At 3 months, overall response rate (ORR) was significantly higher in women administered SAC (80.1%) compared with those who received a placebo (30.5%, P<0.01). Six months after treatment, the ORR for dysmenorrhea was 62.7% in the SAC group and 31.7% in the placebo group (P<0.01). Chronic pelvic pain and defecation pain were significantly improved by SAC compared with placebo (both P<0.05). The incidence rates of total AEs events in the SAC and placebo groups were 6.6% and 9.8%, respectively, and no significant difference was shown between the two groups (P=0.339). CONCLUSION: SAC is well-tolerated and may improve dysmenorrhea in women with endometriosis-associated pain. (Trial registration: ClinicalTrials.gov, No. NCT02031523).

2.
Heliyon ; 10(12): e33100, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38994053

ABSTRACT

Preservation of cultural relics is crucial for cultural sustainability, particularly in the case of cave temples, which are a unique and immovable part of our heritage, nested within mountains. These structures bear immense historical significance and possess considerable economic value, making them vulnerable to criminal activities, notably theft. Establishing a robust physical protection system (PPS) is imperative to safeguard these relics from potential damage. This paper proposes a novel approach for assessing the vulnerability of cave temples' PPS. Based on the fuzzy Petri net (FPN) principle, a comprehensive vulnerability assessment index system was developed within the PPS framework, considering the unique characteristics of cave temples. This study refines the formal definition of the FPN, enhancing its precision and effectiveness for vulnerability assessment. The practicality and effectiveness of the proposed method are verified through simulation experiments. An illustrative example is provided to demonstrate this approach.

3.
World J Gastrointest Oncol ; 16(6): 2842-2861, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994129

ABSTRACT

BACKGROUND: Gastrointestinal neoplasm (GN) significantly impact the global cancer burden and mortality, necessitating early detection and treatment. Understanding the evolution and current state of research in this field is vital. AIM: To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research, focusing on key contributors, institutions, and thematic evolution. METHODS: This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the "bibliometrix" R package, VOSviewer, and CiteSpace. The analysis focused on the distribution of publications, contributions by institutions and countries, and trends in keywords. The methods included data synthesis, network analysis, and visualization of international collaboration networks. RESULTS: This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration. It highlights the United States' critical role in advancing this field, with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute. The last five years, substantial advancements have been made, representing nearly 45% of the examined literature. Publication rates have dramatically increased, from 20 articles in 2002 to 112 in 2022, reflecting intensified research efforts. This study underscores a growing trend toward interdisciplinary and international collaboration, with the Journal of Clinical Oncology standing out as a key publication outlet. This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks. CONCLUSION: This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis. This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy, ultimately enhancing worldwide patient care.

4.
Huan Jing Ke Xue ; 45(7): 4266-4278, 2024 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-39022972

ABSTRACT

Antimony (Sb) is a major pollutant that poses a serious threat to the environment in the mining and processing of nonferrous metals, coexisting with sulfide and oxide of arsenic (As). Microorganisms play an important role in the migration, transformation, and repair of metals in soil. The ecological effects of bioavailable Sb and As on the microbial community in antimony mining areas(mining and smelting areas)are still poorly understood. The Wenzel method and high-throughput 16S rDNA amplicon were used to characterize soil pollution characteristics in different functional areas, and the relationship between the bacterial community and bioavailable concentrations have been investigated comprehensively. The results showed that: Chemical speciation of Sb and As were amorphous, and poorly crystalline hydrous oxides of Fe and Al (F3) > well-crystallized hydrous oxides of Fe and Al (F4) > residual phases (F5) > specifically adsorbed (F2) > non-specifically adsorbed (F1). According to the estimation of the potential ecological risk index (RI) and geo-accumulation index (Igeo), the Sb pollution degree was: smelting area > mining area > contrast area, in which the smelting area showed serious pollution, and the mining area showed moderate to severe pollution. The As pollution degree was: mining area > smelting area > contrast area, in which the mining area and smelting area showed moderate to severe pollution. High-throughput 16S rDNA amplicon showed that Proteobacteria was the most abundant phylum in mining and smelting areas; Kaistobacter, Pseudomonas, Sphingomonas, and Lysobacter were the most abundant microbial genera; Geobacter and Luteolibacter had a high LDA score in mining areas; and Thiobacillus had a high LDA score in antimony-contaminated areas. Spearman correlation analysis, variation partitioning analysis (VPA), and random forest (RF) analysis showed that Sb, As, bioavailable antimony [Sb (Bio)], and bioavailable arsenic [As (Bio)]were the main factors affecting the microbial community structure in different functional areas of antimony ore. Redundancy analysis (RDA) indicated that Sb and its bioavailable concentrations showed uniformly negative associations with the relative abundance of bacteria Nitrospirae and showed a significant positive correlation with Thiobacillus (P<0.05). The in-depth research on the ecological effects of bioavailable Sb and As on the bacterial community provides references and new perspectives for environmental monitoring and management.


Subject(s)
Antimony , Arsenic , Environmental Monitoring , Mining , Soil Microbiology , Soil Pollutants , China , Soil Pollutants/analysis , Bacteria/classification , Bacteria/genetics
5.
ACS Sens ; 9(7): 3754-3762, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-38970501

ABSTRACT

The combination of closed bipolar electrodes (cBPE) with electrochemiluminescence (ECL) imaging has demonstrated remarkable capabilities in the field of bioanalysis. Here, we established a cBPE-ECL platform for ultrasensitive detection of alkaline phosphatase (ALP) and two-dimensional imaging of epidermal growth factor receptor (EGFR). This cBPE-ECL system consists of a high-density gold nanowire array in anodic aluminum oxide (AAO) membrane as the cBPE coupled with ECL of highly luminescent cadmium selenide quantum dots (CdSe QDs) luminophores to achieve cathodic electro-optical conversion. When an enzyme-catalyzed amplification effect of ALP with 4-aminophenyl phosphate monosodium salt hydrate (p-APP) as the substrate and 4-aminophenol (p-AP) as the electroactive probe is introduced, a significant improvement of sensing sensitivity with a detection limit as low as 0.5 fM for ALP on the cBPE-ECL platform can be obtained. In addition, the cBPE-ECL sensing system can also be used to detect cancer cells with an impressive detection limit of 50 cells/mL by labeling ALP onto the EGFR protein on A431 human epidermal cancer cell membranes. Thus, two-dimensional (2D) imaging of the EGFR proteins on the cell surface can be achieved, demonstrating that the established cBPE-ECL sensing system is of high resolution for spatiotemporal cell imaging.


Subject(s)
Alkaline Phosphatase , Electrodes , ErbB Receptors , ErbB Receptors/metabolism , ErbB Receptors/analysis , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/chemistry , Alkaline Phosphatase/analysis , Humans , Limit of Detection , Luminescent Measurements/methods , Electrochemical Techniques/methods , Cell Line, Tumor , Quantum Dots/chemistry , Cadmium Compounds/chemistry , Biosensing Techniques/methods , Selenium Compounds/chemistry , Gold/chemistry , Nanowires/chemistry
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(7): 835-839, 2024 Jul 10.
Article in Chinese | MEDLINE | ID: mdl-38946368

ABSTRACT

OBJECTIVE: To explore the genetic basis for a fetus with nuchal cystic hygroma identified in the first trimester and cholecystomegaly identified in the middle trimester of pregnancy. METHODS: A 27-year-old pregnant woman who had presented at the Antenatal Diagnostic Center of Jinan Maternal and Child Health Care Hospital on October 25, 2018 was selected as the study subject. Chorionic villus sampling was carried out in the first trimester for chromosomal karyotyping and SNP-Array analysis. Amniocentesis was carried out in the second trimester, and peripheral blood of the couple was collected at the same time. Trio whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: No abnormality was found by chromosomal karyotyping and SNP-Array, whilst high-throughput sequencing revealed that the fetus had harbored a heterozygous c.7732A>T (p.K2578X) nonsense variant of the NIPBL gene. Following elected abortion, the autopsy results were consistent with features of Cornelia de Lange syndrome (CdLS). The same variant was detected in neither parents and was unreported in the literature. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as pathogenic (PVS1+PS2+PM2_Supporting+PP3). CONCLUSION: The novel nonsense variant of the NIPBL gene probably underlay the genetic etiology of CdLS in this fetus. Above finding has also enriched the mutational spectrum of the NIPBL gene.


Subject(s)
Cell Cycle Proteins , De Lange Syndrome , Prenatal Diagnosis , Humans , Female , Pregnancy , De Lange Syndrome/genetics , Adult , Prenatal Diagnosis/methods , Cell Cycle Proteins/genetics , Fetus/abnormalities , Exome Sequencing
7.
Schizophr Res Cogn ; 38: 100321, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39040617

ABSTRACT

Patients with schizophrenia show substantial cognitive deficits and abnormalities in neurotransmitter-related levels of mRNA in brain or peripheral blood lymphocytes. However, the relationship of cognitive deficits as measured by the MATRICS battery and mRNA levels in brain or lymphocytes has not been sufficiently explored. We measured levels of methylation or neurotransmitter-related mRNAs in lymphocytes of 38 patients with chronic schizophrenia (CSZ) and 33 non-psychotic controls (controls) by qPCR using TaqMan probes. We assessed cognitive function in these patients and controls with the MATRICS battery. We used correlation analysis and scatter plots to assess the relationship of lymphocyte mRNA levels to MATRICS domain and composite scores. CSZ subjects had a consistently negative correlation between mRNA levels in lymphocytes and MATRICS cognitive variables of speed of processing, attention-vigilance, working memory, visual learning, and overall composite score. It is uncertain whether these negative correlations represent a causative relation between specific mRNA levels and cognitive deficits. Controls had either positive correlations or non-significant correlations between mRNA and most of the MATRICS variables. There were statistically significant differences in the correlations between mRNA and MATRICS variables between CSZ vs controls for several mRNAs (DNMT1, DNMT3A, BDNF, NR3C1, FPRF3, CNTNAP2). Our data show a different relationship between mRNA levels in peripheral blood lymphocytes and MATRICS cognitive variables in CSZ vs controls. The substantive significance of these differences needs further investigation.

8.
Arch Toxicol ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38992170

ABSTRACT

Genetic variants can affect gene expression by altering the level of N6-methyladenosine (m6A) modifications. A better understanding of the association of these genetic variants with susceptibility to cervical cancer (CC) can promote advances in disease screening and treatment. Genome-wide identification of m6A-associated functional SNPs for CC was performed using the TCGA and JENGER databases, incorporating the data from RNA-seq and MeRIP-seq. The screened risk-associated SNP rs1059288 (A>G), which is located in the 3' UTR of TAPBP, was further validated in a case-control study involving 921 cases and 1077 controls. The results revealed a significant association between rs1059288 and the risk of CC (OR 1.48, 95% CI 1.13-1.92). Mechanistically, the presence of the risk G allele of rs1059288 was associated with increased m6A modification of TAPBP compared with the A allele. This modification was facilitated by the m6A methyltransferase METTL14 and the reading protein YTHDF2. Immunohistochemical staining of tissue microarrays containing 61 CC and 45 normal tissues showed an overexpression of TAPBP in CC. Furthermore, the upregulation of TAPBP promoted the growth and migration of CC cells as well as tumor-forming ability, inhibited apoptosis, and conferred increased resistance to commonly used chemotherapeutic drugs such as bleomycin, cisplatin, and doxorubicin. Knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway in CC cells and upregulated certain immune genes including ISG15, IRF3, PTPN6, and HLA-A. These findings offer insights into the involvement of genetic variations in TAPBP in the development and progression of CC.

9.
Chem Commun (Camb) ; 2024 Jul 12.
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.

10.
Article in English | MEDLINE | ID: mdl-38995769

ABSTRACT

OBJECTIVE: This study aimed to evaluate the clinical characteristics and features of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) in differentiating between renal urothelial carcinomas (RUC) and endophytic clear cell renal cell carcinomas (EccRCC). METHODS: A total of 72 RUCs and 120 EccRCCs confirmed by pathology were assessed retrospectively. Both CUS and CEUS were performed within 4 weeks before the surgery. Logistic regression analyses were used to select statistically significant variables of clinical, CUS, and CEUS features for the differentiation of RUC and EccRCC. Sensitivity (SEN), specificity (SPE), and the area under the receiver-operating characteristic curve (AUC) were assessed for diagnostic performance. Inter- and intra-observer agreements of CUS and CEUS features were evaluated using the intra-class correlation coefficient(ICC). RESULTS: Multiple logistic regression analysis demonstrated that clinical (age >50 years old and hematuria), CUS (size <4.0 cm, hypo-echogenicity, irregular shape, hydronephrosis) and CEUS (absence of non-enhancement area, iso- /hypo-enhancement in cortical phase and absence of rim-like enhancement) features were independent factors for RUC diagnosis. When combining clinical characters with CUS and CEUS features into an integrated diagnostic criterion, the AUC reached 0.917 (95% CI 0.873-0.961), with a sensitivity of 95.8% and specificity of 87.5%. ICC ranged from 0.756 to 0.907 for inter-observer agreement and 0.791 to 0.934 for intra-observer agreement for CUS and CEUSfeatures. CONCLUSIONS: The combination of clinical features of age and hematuria with imaging features of CUS and CEUS can be useful for the differentiation between RUC and EccRCC.

11.
Aging Dis ; 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-39012666

ABSTRACT

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

12.
Dig Dis Sci ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020183

ABSTRACT

OBJECTIVE: NK cells play a vital role in tumor immune resistance. Various factors affect NK cell activity. While NK cell dysfunction has been observed in numerous malignancies, the underlying mechanisms in gastric cancer remain unclear. METHOD: Flow cytometry was used to identify the phenotypic distribution and expression of activated receptors on NK cells. ELISA was used to determine the expression of cytokines. We examined the expression of NK cell-related genes and explored their association with survival and prognosis. Additionally, we conducted PCR detection of miR-552-5p expression levels in plasma exosomes of patients and investigated its correlation with phenotypic distribution and activated receptors. We used flow cytometry and ELISA to verify the role of miR-552-5p in NK cell dysfunction. Furthermore, we investigated the potential role of PD-1/PD-L1 in regulating NK cell dysfunction in patients' cells. RESULTS: We observed a significant decrease in the percentage of NKG2D and NKp30 and IFN-γ and TNF-α in patients than in healthy volunteers. Patients with low levels of CD56, CD16, NKG2D, and NKP46 exhibited poorer survival prognoses. Moreover, increased expression levels of plasma exosomal miR-552-5p in patients were negatively associated with NK cell phenotypic distribution and activated receptor expression. MiR-552-5p downregulated the secretion of perforin, granzyme, and IFN-γ as well as the expression of NKp30, NKp46, and NKG2D. Additionally, it suppressed the cytotoxicity of NK cells. The inhibitory effect of miR-552-5p, on NK cell function was reversed when anti-PD-L1 antibodies were used. CONCLUSION: Exosomal miR-552-5p targets the PD-1/PD-L1 axis, leading to impaired NK cell function.

13.
Front Cell Dev Biol ; 12: 1392159, 2024.
Article in English | MEDLINE | ID: mdl-39055651

ABSTRACT

Various methods have been developed so far for detecting N 6-methyladenosine (m6A). The total m6A level or the m6A status at individual positions on mRNA can be detected and quantified through some sequencing-independent biochemical methods, such as LC/MS, SCARLET, SELECT, and m6A-ELISA. However, the m6A-detection techniques relying on high-throughput sequencing have more effectively advanced the understanding about biological significance of m6A-containing mRNA and m6A pathway at a transcriptomic level over the past decade. Various SGS-based (Second Generation Sequencing-based) methods with different detection principles have been widely employed for this purpose. These principles include m6A-enrichment using antibodies, discrimination of m6A from unmodified A-base by nucleases, a fusion protein strategy relying on RNA-editing enzymes, and marking m6A with chemical/biochemical reactions. Recently, TGS-based (Third Generation Sequencing-based) methods have brought a new trend by direct m6A-detection. This review first gives a brief introduction of current knowledge about m6A biogenesis and function, and then comprehensively describes m6A-profiling strategies including their principles, procedures, and features. This will guide users to pick appropriate methods according to research goals, give insights for developing novel techniques in varying areas, and continue to expand our boundary of knowledge on m6A.

14.
Mol Neurobiol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981960

ABSTRACT

Hemorrhagic stroke is a global health problem owing to its high morbidity and mortality rates. Nicotinamide riboside is an important precursor of nicotinamide adenine dinucleotide characterized by a high bioavailability, safety profile, and robust effects on many cellular signaling processes. This study aimed to investigate the protective effects of nicotinamide riboside against collagenase-induced hemorrhagic stroke and its underlying mechanisms of action. An intracerebral hemorrhage model was constructed by stereotactically injecting collagenase into the right striatum of adult male Institute for Cancer Research mice. After 30 minutes, nicotinamide riboside was administered via the tail vein. The mice were sacrificed at different time points for assessments. Nicotinamide riboside reduced collagenase-induced hemorrhagic area, significantly reduced cerebral water content and histopathological damage, promoted neurological function recovery, and suppressed reactive oxygen species production and neuroinflammation. Nicotinamide riboside exerts neuroprotective effects against collagenase-induced intracerebral hemorrhage by inhibiting neuroinflammation and oxidative stress.

15.
BMC Plant Biol ; 24(1): 529, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862926

ABSTRACT

BACKGROUND: The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear. RESULTS: In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding. CONCLUSIONS: In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.


Subject(s)
Aphids , Metabolome , Sorghum , Transcriptome , Sorghum/genetics , Sorghum/parasitology , Sorghum/metabolism , Aphids/physiology , Animals , Gene Expression Profiling , Gene Expression Regulation, Plant , Plant Leaves/metabolism , Plant Leaves/genetics
16.
Chem Sci ; 15(23): 8993-8999, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38873081

ABSTRACT

Aromatization-driven deconstruction and functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis is developed. The aromatization effect was introduced to synergistically drive unstrained cyclic C-C bond cleavage, with the aim of overcoming the ring-size limitation of nitrogen-centered radical induced deconstruction of carbocycles. Herein, we demonstrate the synergistic photoredox/nickel catalyzed deconstructive cross-coupling of spiro dihydroquinazolinones with organic halides. Remarkably, structurally diverse organic halides including aryl, alkenyl, alkynyl, and alkyl bromides were compatible for the coupling. In addition, this protocol is also characterized by its mild and redox-neutral conditions, excellent functional group compatibility, high atom economy, and easy scalability. A telescoped procedure involving condensation and ring-opening/coupling was found to be accessible. This work provides a complementary strategy to the existing radical-mediated C-C bond cleavage of unstrained carbocycles.

17.
Front Pharmacol ; 15: 1366061, 2024.
Article in English | MEDLINE | ID: mdl-38873415

ABSTRACT

Traditionally, pharmacological mammalian/mechanistic targets of rapamycin (mTOR) kinase inhibitors have been used during transplantation and tumor treatment. Emerging pre-clinical evidence from the last decade displayed the surprising effectiveness of mTOR inhibitors in ameliorating Alzheimer's Disease (AD), a common neurodegenerative disorder characterized by progressive cognitive function decline and memory loss. Research shows mTOR activation as an early event in AD development, and inhibiting mTOR may promote the resolution of many hallmarks of Alzheimer's. Aberrant protein aggregation, including amyloid-beta (Aß) deposition and tau filaments, and cognitive defects, are reversed upon mTOR inhibition. A closer inspection of the evidence highlighted a temporal dependence and a hallmark-specific nature of such beneficial effects. Time of administration relative to disease progression, and a maintenance of a functional lysosomal system, could modulate its effectiveness. Moreover, mTOR inhibition also exerts distinct effects between neurons, glial cells, and endothelial cells. Different pharmacological properties of the inhibitors also produce different effects based on different blood-brain barrier (BBB) entry capacities and mTOR inhibition sites. This questions the effectiveness of mTOR inhibition as a viable AD intervention strategy. In this review, we first summarize the different mTOR inhibitors available and their characteristics. We then comprehensively update and discuss the pre-clinical results of mTOR inhibition to resolve many of the hallmarks of AD. Key pathologies discussed include Aß deposition, tauopathies, aberrant neuroinflammation, and neurovascular system breakdowns.

18.
Food Sci Nutr ; 12(6): 4443-4458, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38873454

ABSTRACT

The aim of this study is to combine flaxseed oil (FO), rich in α-linolenic acid (ALA), with Sunite sheep tail fat (STF) through a lipase-catalyzed transesterification reaction, in order to produce an edible oil with a fatty acid ratio suitable for human needs. Initially, the optimal conditions for esterification were determined using the Box-Behnken design, with the measurement criterion being the content of ALA at the sn-2 position. The results indicated that the highest content of sn-2 ALA was obtained under the conditions of using 6.8 wt% Lipozyme®RMIM as the catalyst, a reaction temperature of 57°C, a reaction time of 3.3 h, and a substrate mass ratio of 5.6:4.4 for STF and FO. This led to the rapid breaking and recombining of molecular bonds, resulting in the interesterified fat (IF) with the highest content of ALA at the sn-2 position. Comparing STF and FO, IF exhibited excellent fatty acid composition and content. Furthermore, IF had a lower melting point and crystallization temperature compared to STF, and its solid fat content decreased with increasing temperature, completely melting at temperatures above 30°C. Thus, IF is a synthesized fat with excellent properties from both animal and vegetable sources.

19.
Front Psychol ; 15: 1360951, 2024.
Article in English | MEDLINE | ID: mdl-38873511

ABSTRACT

Background: With increasing gaps between the rich and poor, potential risk factors for class conflict have attracted increasing attention from researchers. Although cognitive factors are known to be significant predictors of class-conflict behavior, limited attention has been paid to competence stereotypes of the upper class. When considering economic inequality, people pay more attention to competence stereotypes of the upper class, which may have adverse effects. This study aimed to investigate the relationship between competence stereotypes held by the lower class about the upper class and class conflict, and to test the mediating role of intergroup envy in this relationship and the moderating role of upward social mobility belief. Methods: Data were collected from a convenience sample from a comprehensive university in China. Based on scores on subjective and objective class scales, 284 lower-class college students (103 males and 181 females) aged 18-24 were selected to participate (both their subjective and objective scores were lower than 3 points). Their endorsement of upper-class competence stereotypes, intergroup envy, upward social mobility beliefs, and class conflict were measured using a well-validated self-report questionnaire. Results: The main data were analyzed using correlation analysis, the SPSS macro PROCESS (Model 7), and simple slope analysis. The results show a significant positive correlation between competence stereotypes held by lower-class college students toward the higher class and class conflict, and this connection was mediated by intergroup envy. Moreover, the indirect effect of intergroup envy on this link was moderated by upward social mobility beliefs; this effect was stronger for college students with lower upward social mobility beliefs. Conclusion: This study broadens our understanding of how and when competence stereotypes among the lower class concerning the upper class are related to class conflict. Researchers and policymakers should pay special attention to competence stereotypes of the upper class, especially intergroup envy and class conflict among lower-class individuals with lower levels of upward social mobility beliefs.

20.
Chem Sci ; 15(25): 9557-9565, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38939138

ABSTRACT

Sorption-based atmospheric water-harvesting (AWH) could help to solve global freshwater scarcity. The search for adsorbents with high water-uptake capacity at low relative humidity, rapid adsorption-desorption kinetics and high thermal conductivity is a critical challenge in AWH. Herein, we report a MAF-4 (aka ZIF-8)-derived nanoporous carbon (NPCMAF-4-800) with multiple N-doped sites, considerable micropore characteristics and inherent photothermal properties, for efficient water production in a relatively arid climate. NPCMAF-4-800 exhibited optimal water-sorption performance of 306 mg g-1 at 40% relative humidity (RH). An excellent sunlight-absorption rate was realized (97%) attributed to its high degree of graphitization. A proof-of-concept device was designed and investigated for the practical harvesting of water from the atmosphere using natural sunlight. NPCMAF-4-800 achieved an unprecedentedly high water production rate of 380 mg g-1 h-1 at 40% RH, and could produce 1.77 L kg-1 freshwater during daylight hours in an outdoor low-humidity climate of ∼25 °C and 40% RH. These findings may shed light on the potential of MOF-derived porous carbons in the AWH field, and inspire the future development of solar-driven water-generation systems.

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