ABSTRACT
Coral reefs are among the most diverse and valuable ecosystems on the planet, providing numerous benefits to human societies, including fisheries, coastal protection, and biodiversity conservation. In order to effectively manage and conserve coral reefs, it is essential to understand the value of the ecosystem services they provide. The System of Environmental-Economic Accounting (SEEA) framework offers a comprehensive approach for accounting for ecosystem services, which can be useful for assessing the value of natural environments. While the validity of SEEA for many marine ecosystems is increasingly acknowledged, there remains a scarcity of studies that have investigated SEEA in the context of coral reef ecosystems. To bridge this gap, this study offers extensive examination and investigates the evolution of coral reef ecosystem service research under the SEEA framework in over nearly three decades, providing a rich dataset for understanding trends and gaps. The research findings reveal interdisciplinary methodological integration in coral reef ecosystem research, incorporating remote sensing, environmental science, ecology, environmental economics, ecological economics, computer science, and citizen science. Across different time periods, within the shared focus of coral reef health and sustainability, there has been a transition from concerns about the impacts of human activities to a concentration on climate change, supported by empirical evidence and case studies. These research results contribute to our better understanding of the value of coral reef ecosystems.
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Enantioselective recognition is a fundamental property of chiral linkers in chiral metal-organic frameworks (CMOFs). However, clarifying the efficient enantioselective discrimination tailored by achiral linkers remains challenging to explain the chiral recognition mechanism and efficiency. Here, two CMOFs ([Zn2(l-Phe)2(bpa)2]n and [Zn2(l-Phe)2(bpe)2]n) with the completely different enantioselective recognition are synthesized from different nonchiral ligands and the same chiral ligands. The enantioselective recognition of CMOF is undoubtedly related to l-Phe, which differs in the hydrogen bonding to the Trp enantiomer. However, the electrochemical signals are weak and undifferentiated. [Zn2(l-Phe)2(bpe)2]n produces a flattened coplanar conformation with the -CâC- tether in the achiral ligand. The flattened achiral bpee ligand and its surrounding chiral phenylalanine molecules interact through multiple π-π stacking and hydrogen bonding, which together create a chiral sensor that facilitates the recognition of l-Trp. However, [Zn2(l-Phe)2(bpa)2]n produces a stepped conformation due to the -C-C- tether in the achiral ligand; despite the recognition effect of bpea, the recognition is unsatisfactory. Therefore, the chiral recognition of the two CMOFs stems from the synergistic effect between chiral and achiral ligands. This work shows that nonchiral ligands are also crucial in determining enantiomeric discrimination and opens up a new avenue for designing chiral materials.
ABSTRACT
Multiple myeloma (MM) is a plasma cell malignancy considered incurable despite the recent therapeutic advances. Effective targeted therapies are therefore needed. Our previous studies proved that inhibiting CDK7 impairs the cell cycle and metabolic programs by disrupting E2F1 and MYC transcriptional activities, making it an appealing therapeutic target for MM. Given that CDK7 and BRD4 operate in two distinct regulatory axes in MM, we hypothesized that targeting these two complementary pathways simultaneously would lead to a deeper and more durable response. Indeed, combination therapy had superior activity against MM cell growth and viability, and induced apoptosis to a greater extent than single-agent therapy in both cell lines and patient cells. This synergistic activity was also observed in Waldenström's Macroglobulinemia (WM) cells and with other inhibitors of E2F1 activity. Dual inhibition effectively impaired the MYC and E2F transcriptional programs and MM tumor growth and progression in xenograft animal models, providing evidence for combination therapy's potential as a therapeutic strategy in MM and WM.
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Background: Chronic respiratory disease is an important public health problem in the United States and globally. Diet, an important part of a healthy lifestyle, is also relevant to chronic respiratory health. We aimed to explore the relationship between overall dietary quality and the risk of chronic respiratory disease (CRD), include chronic bronchitis (CB), emphysema and asthma. Method: A total of 4,499 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2017-2018. Diet quality was assessed using 2 day, 24 h dietary recall data and quantified as the Healthy Diet Index (HEI)-2020 score. Binary logistic regression models, restricted cubic splines (RCS) and generalized additive modeling (GAM), the weighted quartile sum (WQS) and qgcom models were used to assess the relationship between HEI-2020 scores and risk of CB, emphysema and asthma. Results: High HEI-2020 scores are associated with low risk of chronic respiratory disease (CB: 0.98, 0.97-0.99; emphysema: 0.98, 0.97-0.99; asthma: 0.98, 0.97-0.99) and consistent results across different dietary variable categorization (Tertile: CB: 0.58, 0.42-0.81; asthma: 0.51, 0.35-0.74; Quartile: CB: 0.57, 0.34-0.97; asthma: 0.56, 0.36-0.86) and different weighting models. Negative dose-response relationship between dietary quality and risk of chronic respiratory disease also shown in RCS and GAM models. The WQS and qgcom models also showed a healthy mixing effect of dietary components on respiratory disease, with high-quality proteins, vegetables, and fruits making the heaviest contributions. Conclusion: Higher HEI-2020 scores were associated with lower risk of CB, emphysema, and asthma. Following Dietary Guidelines for Americans 2020-2025 could support enhanced respiratory health.
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Chiral inversions of enantiomers have significantly different biological activities, so it is important to develop simple and effective methods to efficiently identify optically pure compounds. Inspired by enzyme catalysis, the construction of chiral microenvironments resembling enzyme pockets in the pore space structure of metal-organic frameworks (MOFs) to achieve asymmetric enantioselective recognition and catalysis has become a new research hotspot. Here, a super-stable porphyrin-containing material PCN-224 is constructed by solvothermal method and a chiral microenvironment around the existing catalytic site of the material is created by post-synthesis modifications of the histidine (His) enantiomers. Experimental and theoretical calculations results show that the modulation of chiral ligands around Zr oxide clusters produces different spatial site resistances, which can greatly affect the adsorption and catalytic level of the enantiomeric molecules of tryptophan guests, resulting in a good enantioselective property of the material. It provides new ideas and possibilities for future chiral recognition and asymmetric catalysis.
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Chirality has an important impact on chemical and biological research, as most active substances are chiral. In recent decades, metal-organic frameworks (MOFs), which are assembled from metal ions or clusters and organic linkers via metal-ligand bonding, have attracted considerable scientific interest due to their high crystallinity, exceptional porosity and tunable pore sizes, high modularity, and diverse functionalities. Since the discovery of the first functional chiral metal-organic frameworks (CMOFs), CMOFs have been involved in a variety of disciplines such as chemistry, physics, optics, medicine, and pharmacology. The introduction of defect engineering theory into CMOFs allows the construction of a class of defective CMOFs with high hydrothermal stability and multi-stage pore structure. The introduction of defects not only increases the active sites but also enlarges the pore sizes of the materials, which improves chiral recognition, separation, and catalytic reactions, and has been widely investigated in various fields. This review describes the design and synthesis of various defective CMOFs, their characterization, and applications. Finally, the development of the materials is summarized, and an outlook is given. This review should provide researchers with an insight into the design and study of complex defective CMOFs.
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An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was utilized to develop a technique for the simultaneous quantification of icariin and its primary metabolites in mouse urine. The levels of icariin, icariside â , icariside â ¡, baohuoside â ¡, wushanicaritin, icaritin, and desmethylicaritin in mouse urine were analyzed subsequent to the oral administration of an icariin suspension. This study aimed to preliminarily investigate the excretion profile of icariin in mice. Using an aqueous solution containing 0.1% formic acid (A) and an acetonitrile solution containing 0.1% formic acid (B) as the mobile phases, icariin and its major metabolites demonstrated satisfactory linearity over the concentration range of 0.25-800 ng·mL-1. The precision and accuracy of intra-day and inter-day measurements were all found to be within 15%. Seventy-two hours after the intragastric administration of icariin suspension to a mouse, the cumulative urinary excretion of icariin, icariside â , icariside â ¡, baohuoside â ¡, wushanicaritin, icaritin, and desmethylicaritin was quantified as 13.48, 18.70, 2,627.51, 2.04, 10.04, 3,420.44, and 735.13 ng, respectively. The UPLC-MS/MS method developed in this research is characterized by its simplicity, sensitivity, and speed, making it well-suited for the concurrent quantification of icariin and its associated metabolites in urine. Additionally, it is appropriate for analyzing urine samples that may contain multiple drugs in future investigations.
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BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.
Subject(s)
Fatigue , Peritoneal Dialysis , Humans , Male , Female , Peritoneal Dialysis/adverse effects , Middle Aged , Adult , China/epidemiology , Fatigue/etiology , Anxiety/etiology , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/complications , Pruritus/etiology , Aged , Symptom Assessment , Factor Analysis, Statistical , Cross-Sectional Studies , East Asian PeopleABSTRACT
ABSTRACT: Because multiple myeloma (MM) poses a formidable therapeutic challenge despite recent progress, exploring novel targets is crucial. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) emerges as a promising paracaspase with druggable potential, especially unexplored in MM. Our study provided compelling evidence demonstrating a statistically significant elevation of MALT1 expression in human primary MM cells. Moreover, elevated MALT1 expression was associated with a poorer prognosis in MM. Genetic deletion of MALT1 reduced cell growth, colony formation, and tumor growth in vivo. Pharmacological inhibition with 1 µM of a small-molecular MALT1 inhibitor, Mi-2, effectively inhibited cell growth, inducing mitochondria-dependent apoptotic cell death. Mechanistically, MALT1 inhibition disrupted diverse signal transduction pathways, notably impeding nuclear factor κB (NF-κB). Significantly, the inhibition of MALT1 demonstrated a substantial suppression of NF-κB activation by elevating inhibitor of NF-κB, disrupting the nuclear localization of p65 and c-REL. This effect was observed in both the basal state and when stimulated by B-cell maturation antigen, highlighting the pivotal role of MALT1 inhibition in influencing MM cell survival. It was noteworthy that Mi-2 induces properties associated with immunogenic cell death (ICD), as evidenced by increased calreticulin, adenosine triphosphate release, and high-mobility group protein B1 upregulation, consequently triggering ICD-associated immune activation and enhancing CD8+ T-cell cytotoxicity in vitro. In conclusion, our research highlights MALT1 as a promising druggable target for therapeutic interventions in MM, providing insights into its molecular mechanisms in MM progression.
Subject(s)
B-Cell Maturation Antigen , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein , Multiple Myeloma , NF-kappa B , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/antagonists & inhibitors , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/metabolism , Humans , Multiple Myeloma/drug therapy , Multiple Myeloma/metabolism , Multiple Myeloma/pathology , NF-kappa B/metabolism , Animals , Mice , B-Cell Maturation Antigen/metabolism , Cell Line, Tumor , Apoptosis/drug effects , Signal Transduction/drug effects , Cell Proliferation/drug effects , Cell Death/drug effects , Gene Expression Regulation, Neoplastic/drug effectsABSTRACT
Sleep is a highly intricate biological phenomenon, and its disorders play a pivotal role in numerous diseases. However, the specific regulatory mechanisms remain elusive. In recent years, the role of mitochondria in sleep disorders has gained considerable attention. Sleep deprivation not only impairs mitochondrial morphology but also decreases the number of mitochondria and triggers mitochondrial dysfunction. Furthermore, mitochondrial dysfunction has been implicated in the onset and progression of various sleep disorder-related neurological diseases, especially neurodegenerative conditions. Therefore, a greater understanding of the impact of sleep disorders on mitochondrial dysfunction may reveal new therapeutic targets for neurodegenerative diseases. In this review, we comprehensively summarize the recent key findings on the mechanisms underlying mitochondrial dysfunction caused by sleep disorders and their role in initiating or exacerbating common neurodegenerative diseases. In addition, we provide fresh insights into the diagnosis and treatment of sleep disorder-related diseases.
Subject(s)
Mitochondria , Neurodegenerative Diseases , Sleep Wake Disorders , Humans , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/physiopathology , Sleep Wake Disorders/physiopathology , Sleep Wake Disorders/complications , Sleep Wake Disorders/metabolism , Mitochondria/metabolism , Mitochondria/pathology , Animals , Mitochondrial Diseases/physiopathology , Mitochondrial Diseases/complications , Mitochondrial Diseases/metabolismABSTRACT
[This corrects the article DOI: 10.1021/acsomega.3c03428.].
ABSTRACT
The circulating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant presents an ongoing challenge for surveillance and detection. It is important to establish an assay for SARS-CoV-2 antibodies in vaccinated individuals. Numerous studies have demonstrated that binding antibodies (such as S-IgG and N-IgG) and neutralizing antibodies (Nabs) can be detected in vaccinated individuals. However, it is still unclear how to evaluate the consistency and correlation between binding antibodies and Nabs induced by inactivated SARS-CoV-2 vaccines. In this study, serum samples from humans, rhesus macaques, and hamsters immunized with inactivated SARS-CoV-2 vaccines were analyzed for S-IgG, N-IgG, and Nabs. The results showed that the titer and seroconversion rate of S-IgG were significantly higher than those of N-IgG. The correlation between S-IgG and Nabs was higher compared to that of N-IgG. Based on this analysis, we further investigated the titer thresholds of S-IgG and N-IgG in predicting the seroconversion of Nabs. According to the threshold, we can quickly determine the positive and negative effects of the SARS-CoV-2 variant neutralizing antibody in individuals. These findings suggest that the S-IgG antibody is a better supplement to and confirmation of SARS-CoV-2 vaccine immunization.
Subject(s)
Edema , Snake Bites , Humans , Snake Bites/complications , Male , China , Female , Adult , Edema/etiology , Middle Aged , Pain/etiology , Pain Management/methodsABSTRACT
Chiral metal-organic frameworks (MOFs) have attracted much attention due to their highly tunable regular microporous structures. However, chiral electrochemical recognition based on chiral MOFs is often limited by poor charge separation and slow charge transfer kinetics. In this case, C60 can be encapsulated into the cavity of [La(BTB)]n by virtue of host-guest interactions through π-π stacking to synthesize the chiral composite C60@[La(BTB)]n and amplify electrochemically controlled enantioselective interactions with the target enantiomers. A large electrostatic potential difference is generated in chiral C60@[La(BTB)]n due to the host-guest interaction and the inhomogeneity of the charge distribution, leading to the generation of a strong built-in electric field and thus an overall enhancement of the conductivity of the chiral material. Their enantioselective detection of tryptophan enantiomers was demonstrated by electrochemical measurement. The results showed that chiral MOF materials can be used for enantiomeric recognition. It is worth noting that this new material derived from the concept of host-guest interaction to enhance charge separation opens up unprecedented possibilities for future enantioselective recognition and separation.
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Blood-brain barrier (BBB) disruption following ischemic stroke (IS) can induce significant aftereffects. Elevated calmodulin (CaM) expression following stroke causes calcium overload-a key contributor to BBB collapse. Trifluoperazine (TFP), a CaM inhibitor, reduces CaM overexpression following IS. However, it remains unclear whether TFP participates in BBB repair after IS. We administered TFP to mice subjected to middle cerebral artery occlusion (MCAO) and bEnd.3 cells subjected to oxygen-glucose deprivation (OGD). TFP treatment in MCAO mice reduced cerebral CaM expression and infarct size and decreased BBB permeability. OGD-treated bEnd.3 cells showed significantly increased CaM protein levels and reduced tight junction (TJ) protein levels; these changes were reversed by TFP treatment. Our results found that TFP administration in mice inhibited actin contraction following cerebral ischemia-reperfusion by suppressing the MLCK/p-MLC pathway, thereby attenuating cell retraction, improving TJ protein integrity, and reducing BBB permeability. Consequently, this treatment may promote neurological function recovery after IS.
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Chiral self-assembly is the spontaneous organization of individual building blocks from chiral (bio)molecules to macroscopic objects into ordered superstructures. Chiral self-assembly is ubiquitous in nature, such as DNA and proteins, which formed the foundation of biological structures. In addition to chiral (bio) molecules, chiral ordered superstructures constructed by self-assembly have also attracted much attention. Chiral self-assembly usually refers to the process of forming chiral aggregates in an ordered arrangement under various non-covalent bonding such as H-bond, π-π interactions, van der Waals forces (dipole-dipole, electrostatic effects, etc.), and hydrophobic interactions. Chiral assembly involves the spontaneous process, which followed the minimum energy rule. It is essentially an intermolecular interaction force. Self-assembled chiral materials based on chiral recognition in electrochemistry, chiral catalysis, optical sensing, chiral separation, etc. have a broad application potential with the research development of chiral materials in recent years.
ABSTRACT
The introduction of chirality into easy-scalable metal-organic frameworks (MOFs) gives rise to the development of advanced electrochemical sensors. However, integrating chirality by directly connecting metal ions and chiral ligands is unpredictable. Postmodification synthesis is a common method for synthesizing chiral MOFs, but it reduces the size of chiral channels and poses obstacles to the approach of chiral guest molecules. In this work, missing connection defects were introduced into the chiral MOFs through defect engineering strategies, which enhance the recognition of the target enantiomers. pH can tune enantioselectivity reversal in defective chiral MOFs. The chiral MOFs show enantioselectivity for d-Trp at pH = 5 and l-Trp at pH = 8. From the results of zeta potential, regardless of pH 5 or 8, the chiral MOF has a positive potential. The chiral MOFs are positively charged, while tryptophan is negatively charged when pH = 8. The difference in the positive and negative charge interactions between the two amino acids and chiral MOFs leads to chiral recognition. However, the difference in π-π interaction between chiral MOF and Trp enantiomers mainly drives chiral recognition under pH = 5. This study paves a pathway for the synthesis of defective chiral MOFs and highlights the pH-tuned enantioselectivity reversal.
Subject(s)
Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Amino Acids , Tryptophan , Metals , Hydrogen-Ion ConcentrationABSTRACT
Ischemic stroke is one of the most vital causes of high neurological morbidity and mortality in the world. Preconditioning exercise is considered as the primary prevention of stroke to resistance to subsequent injury. We tried to research the underlying biological mechanisms of this exercise. Forty-two SD rats were randomly divided into three groups: middle cerebral artery occlusion (MCAO) group, exercise group with MCAO (EX + MCAO) group, and sham group, with 14 rats in each group. The EX + MCAO group underwent exercise preconditioning for 3 weeks before occlusion, and the other two groups were fed and exercised normally. After 3 weeks, MCAO model was made by thread plug method in the EX + MCAO group and MCAO group. After successful modeling, the Longa scale was used to evaluate the neurological impairment of rats at day 0, day 1, and day 2. The rats in each group were killed on the third day after modeling. TTC staining measured the infarct volume of each group. The morphology and apoptosis of cortical cells were observed by HE and Tunel staining. Three rats in each group underwent high-throughput sequencing. Bioinformatic analysis was used to find the deferentially expressed genes (DEGs) and predict the transcription factor binding sites (TFBS) of the next-generation sequencing results. Gene enrichment (GSEA) was used to analyze potential functional genes and their corresponding signaling pathways. The Longa scale showed EX + MCAO group had the neurological function better than the modeling group (P < 0.001). TTC staining showed that the infarct size of EX + MCAO group was less than MCAO group (P < 0.05). HE and Tunel staining showed that the cells in the EX + MCAO group and the sham group had normal morphology and fewer apoptotic cells than MCAO group. A new gene named 7994 was discovered and TFBS of this gene was predicted, which could interact with key genes such as Foxd3, Foxa2, NR4A2, SP1, CEBPA, and SOX10. GSEA showed that EX + MCAO group could promote and regulate angiogenesis and apoptosis through PI3K-AKT pathway. Preconditioning exercise could improve nerve function and reduce infarct size in rats. The underlying mechanism is to regulate the PI3K-AKT pathway through several key genes, promote cerebral angiogenesis, and reduce apoptosis.
Subject(s)
Brain Injuries , Brain Ischemia , Ischemic Stroke , Stroke , Rats , Animals , Rats, Sprague-Dawley , Ischemic Stroke/prevention & control , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Infarction, Middle Cerebral Artery , Brain/metabolism , Repressor Proteins , Forkhead Transcription Factors/metabolismABSTRACT
Purpose: Early-stage lung cancer is typically characterized clinically by the presence of isolated lung nodules. Thousands of cases are examined each year, and one case usually contains numerous lung CT slices. Detecting and classifying early microscopic lung nodules is demanding due to their diminutive dimensions and restricted characterization capabilities. Therefore, a lung nodule classification model that performs well and is sensitive to microscopic lung nodules is needed to accurately classify lung nodules. Methods: This paper uses the Resnet34 network as a basic classification model. A new cascade lung nodule classification method is proposed to classify lung nodules into 6 classes instead of the traditional 2 or 4 classes. It can effectively classify six different nodule types including ground-glass and solid nodules, benign and malignant nodules, and nodules with predominantly ground-glass or solid components. Results: In this paper, the traditional multi-classification method and the cascade classification method proposed in this paper were tested using real lung nodule data collected in the clinic. The test results demonstrate that the cascade classification method in this study achieves an accuracy of 80.04%, outperforming the conventional multi-classification approach. Conclusions: Different from the existing methods for categorizing the benign and malignant nature of lung nodules, the approach presented in this paper can classify lung nodules into 6 categories more accurately. At the same time, This paper proposes a rapid, precise, and dependable approach for classifying six distinct categories of lung nodules, which increases the accuracy categorization compared with the traditional multivariate categorization method.
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Experience-driven alterations in neuronal activity are followed by structural-functional modifications allowing cells to adapt to these activity changes. Structural plasticity has been observed for cortical principal cells. However, how GABAergic interneurons respond to experience-dependent network activity changes is not well understood. We show that parvalbumin-expressing interneurons (PVIs) of the dentate gyrus (DG) possess dendritic spines, which undergo behaviorally induced structural dynamics. Glutamatergic inputs at PVI spines evoke signals with high spatial compartmentalization defined by neck length. Mice experiencing novel contexts form more PVI spines with elongated necks and exhibit enhanced network and PVI activity and cFOS expression. Enhanced green fluorescent protein reconstitution across synaptic partner-mediated synapse labeling shows that experience-driven PVI spine growth boosts targeting of PVI spines over shafts by glutamatergic synapses. Our findings propose a role for PVI spine dynamics in regulating PVI excitation by their inputs, which may allow PVIs to dynamically adjust their functional integration in the DG microcircuitry in relation to network computational demands.