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1.
ACS Org Inorg Au ; 4(3): 306-318, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38855334

ABSTRACT

Electrochemical water oxidation is known as the anodic reaction of water splitting. Efficient design and earth-abundant electrocatalysts are crucial to this process. Herein, we report a family of catalysts (1-3) bearing bis(benzimidazole)pyrazolide ligands (H 2 L1-H 2 L3). H 2 L3 contains electron-donating substituents and noninnocent components, resulting in catalyst 3 exhibiting unique performance. Kinetic studies show first-order kinetic dependence on [3] and [H2O] under neutral and alkaline conditions. In contrast to previously reported catalyst 1, catalyst 3 exhibits an insignificant kinetic isotope effect of 1.25 and zero-order dependence on [NaOH]. Based on various spectroscopic methods and computational findings, the L3Co2 III(µ-OH) species is proposed to be the catalyst resting state and the nucleophilic attack of water on this species is identified as the turnover-limiting step of the catalytic reaction. Computational studies provided insights into how the interplay between the electronic effect and ligand noninnocence results in catalyst 3 acting via a different reaction mechanism. The variation in the turnover-limiting step and catalytic potentials of species 1-3 leads to their catalytic rates being independent of the overpotential, as evidenced by Eyring analysis. Overall, we demonstrate how ligand design may be utilized to retain good water oxidation activity at low overpotentials.

2.
Integr Zool ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38897980

ABSTRACT

Intertidal organisms usually live near their upper thermal limits, and are vulnerable to future global warming. As a vital response to thermal stress, thermoregulatory strategy in physiological and behavioral performance is essential for organisms coping with thermal stress and surviving the changing world. To investigate the relationship between the thermoregulatory strategy and habitat temperature, in the present study, we comparatively investigated the thermal responsive strategy among different geographic populations of the supralittoral snail Littoraria sinensis by determining snails' cardiac function and behavioral performance. Our results indicated that populations inhabiting high ambient temperatures had higher sublethal temperatures (i.e. Arrhenius breakpoint temperatures, ABTs, the temperature at which the heart rate shapely decreases with further heating) and lethal temperatures (i.e. Flatline temperatures, FLTs, the temperature at which heart rate ceases), and behaved less actively (e.g. shorter moving distances and shorter moving time) in the face of high and rising temperatures-a physiological fight strategy. On the other hand, populations at relatively low ambient temperatures had relatively lower physiological upper thermal limits with lower ABTs and FLTs and moved more actively in the face of high and rising temperatures-a behavioral flight strategy. These results demonstrate that the thermoregulatory strategies of the snails are closely related to their habitat temperatures and are different among populations surviving divergent thermal environments.

3.
J Am Chem Soc ; 146(21): 14754-14764, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38754363

ABSTRACT

Lithium-sulfur (Li-S) batteries are highly considered as next-generation energy storage techniques. Weakly solvating electrolyte with low lithium polysulfide (LiPS) solvating power promises Li anode protection and improved cycling stability. However, the cathodic LiPS kinetics is inevitably deteriorated, resulting in severe cathodic polarization and limited energy density. Herein, the LiPS kinetic degradation mechanism in weakly solvating electrolytes is disclosed to construct high-energy-density Li-S batteries. Activation polarization instead of concentration or ohmic polarization is identified as the dominant kinetic limitation, which originates from higher charge-transfer activation energy and a changed rate-determining step. To solve the kinetic issue, a titanium nitride (TiN) electrocatalyst is introduced and corresponding Li-S batteries exhibit reduced polarization, prolonged cycling lifespan, and high actual energy density of 381 Wh kg-1 in 2.5 Ah-level pouch cells. This work clarifies the LiPS reaction mechanism in protective weakly solvating electrolytes and highlights the electrocatalytic regulation strategy toward high-energy-density and long-cycling Li-S batteries.

4.
Sci Rep ; 14(1): 11486, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38769368

ABSTRACT

The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3-4. In addition to stage, intrahepatic metastasis and Child-Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p < 0.05). The OS (14.63 pg/mL as cutoff value) and PFS (9.85 pg/mL as cutoff value) of patients with low IL-6 levels exceeded those with high levels (21.0 and 6.9, 15.8 and 10.0 months, respectively). The risks of death and disease progression were reduced by 63.0% (HR = 0.37, 95% CI: 0.19-0.72) and 43.0% (HR = 0.57, 95% CI: 0.22-1.47), respectively. Pre-treatment IL-6 levels may be a simple and effective prognostic indicator for patients with advanced HCC treated with radiotherapy combined with immunotargeted therapy.


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Hepatocellular , Cytokines , Indoles , Liver Neoplasms , Quinolines , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/radiotherapy , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Male , Female , Middle Aged , Quinolines/therapeutic use , Quinolines/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Aged , Indoles/therapeutic use , Indoles/administration & dosage , Prognosis , Cytokines/blood , Adult , Interleukin-6/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects
5.
Neuroscience ; 551: 103-118, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38810691

ABSTRACT

Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg-1·d-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 µM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.


Subject(s)
G(M1) Ganglioside , Neurons , Neuroprotective Agents , Rats, Sprague-Dawley , Reperfusion Injury , Signal Transduction , Animals , Reperfusion Injury/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/pathology , G(M1) Ganglioside/pharmacology , Male , Neurons/metabolism , Neurons/drug effects , Neurons/pathology , Neuroprotective Agents/pharmacology , Signal Transduction/drug effects , Signal Transduction/physiology , Brain Ischemia/metabolism , Brain Ischemia/drug therapy , Brain Ischemia/pathology , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/metabolism , Rats , Apoptosis/drug effects , Apoptosis/physiology , Spectrin/metabolism
6.
Sci Total Environ ; 927: 172010, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38575020

ABSTRACT

Climate change and human activity are essential factors affecting marine biodiversity and aquaculture, and understanding the impacts of human activities on the genetic structure to increasing high temperatures is crucial for sustainable aquaculture and marine biodiversity conservation. As a commercially important bivalve, the Manila clam Ruditapes philippinarum is widely distributed along the coast of China, and it has been frequently introduced from Fujian Province, China, to other regions for aquaculture. In this study, we collected four populations of Manila clams from different areas to evaluate their thermal tolerance by measuring cardiac performance and genetic variations using whole-genome resequencing. The upper thermal limits of the clams showed high variations within and among populations. Different populations displayed divergent genetic compositions, and the admixed population was partly derived from the Zhangzhou population in Fujian Province, implying a complex genomic landscape under the influence of local genetic sources and human introductions. Multiple single nucleotide polymorphisms (SNPs) were associated with the cardiac functional traits, and some of these SNPs can affect the codon usage and the structural stability of the resulting protein. This study shed light on the importance of establishing long-term ecological and genetic monitoring programs at the local level to enhance resilience to future climate change.


Subject(s)
Aquaculture , Bivalvia , Animals , China , Bivalvia/genetics , Bivalvia/physiology , Climate Change , Polymorphism, Single Nucleotide , Adaptation, Physiological/genetics
7.
World J Gastrointest Oncol ; 16(2): 372-385, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38425405

ABSTRACT

BACKGROUND: Circulating tumor cell (CTC) count and neutrophil-to-lymphocyte ratio (NLR) are both closely associated with the prognosis of hepatocellular carcinoma (HCC). AIM: To investigate the prognostic value of combining these two indicators in HCC. METHODS: Clinical data were collected from patients with advanced HCC who received immune therapy combined with targeted therapy at the Department of Oncology, the Affiliated Hospital of Southwest Medical University, Sichuan, China, from 2021 to 2023. The optimal cutoff values for CTC programmed death-ligand 1 (PD-L1) (+) > 1 or CTC PD-L1 (+) ≤ 1 and NLR > 3.89 or NLR ≤ 3.89 were evaluated using X-Tile software. Patients were categorized into three groups based on CTC PD-L1 (+) counts and NLR: CTC-NLR (0), CTC-NLR (1), and CTC-NLR (2). The relationship between CTC-NLR and clinical variables as well as survival rates was assessed. RESULTS: Patients with high CTC PD-L1 (+) expression or NLR at baseline had shorter median progression-free survival (mPFS) and median overall survival (mOS) than those with low levels of CTC PD-L1 (+) or NLR (P < 0.001). Meanwhile, patients in the CTC-NLR (2) group showed a significant decrease in mPFS and mOS. Cox regression analysis revealed that alpha-fetoprotein (AFP), CTC PD-L1 (+), and CTC-NLR were independent predictors of OS. The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months (0.821) and 18 months (0.821) was superior to that of AFP and CTC PD-L1 (+). CONCLUSION: HCC patients with high CTC PD-L1 (+) or NLR expression tend to exhibit poor prognosis, and a high baseline CTC-NLR score may indicate low survival. CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

8.
Nat Microbiol ; 9(2): 405-420, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38316932

ABSTRACT

Tc toxins are virulence factors of bacterial pathogens. Although their structure and intoxication mechanism are well understood, it remains elusive where this large macromolecular complex is assembled and how it is released. Here we show by an integrative multiscale imaging approach that Yersinia entomophaga Tc (YenTc) toxin components are expressed only in a subpopulation of cells that are 'primed' with several other potential virulence factors, including filaments of the protease M66/StcE. A phage-like lysis cassette is required for YenTc release; however, before resulting in complete cell lysis, the lysis cassette generates intermediate 'ghost' cells, which may serve as assembly compartments and become packed with assembled YenTc holotoxins. We hypothesize that this stepwise mechanism evolved to minimize the number of cells that need to be killed. The occurrence of similar lysis cassettes in diverse organisms indicates a conserved mechanism for Tc toxin release that may apply to other extracellular macromolecular machines.


Subject(s)
Virulence Factors , Yersinia , Yersinia/chemistry , Endopeptidases
9.
Nanoscale Adv ; 6(3): 947-959, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38298598

ABSTRACT

Multivalent ligands hold promise for enhancing avidity and selectivity to simultaneously target multimeric proteins, as well as potentially modulating receptor signaling in pharmaceutical applications. Essential for these manipulations are nanosized scaffolds that precisely control ligand display patterns, which can be achieved by using polyproline oligo-helix macrocyclic nanoscaffolds via selective binding to protein oligomers and cell surface receptors. This work focuses on synthesis and structural characterization of different-sized polyproline tri-helix macrocyclic (PP3M) scaffolds. Through combined analysis of circular dichroism (CD), small- and wide-angle X-ray scattering (SWAXS), electron spin resonance (ESR) spectroscopy, and molecular modeling, a non-coplanar tri-helix loop structure with partially crossover helix ends is elucidated. This structural model aligns well with scanning tunneling microscopy (STM) imaging. The present work enhances the precision of nanoscale organic synthesis, offering prospects for controlled ligand positioning on scaffolds. This advancement paves the way for further applications in nanomedicine through selective protein interaction, manipulation of cell surface receptor functions, and developments of more complex polyproline-based nanostructures.

10.
Angew Chem Int Ed Engl ; 63(19): e202400343, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38323892

ABSTRACT

Lithium polysulfides (LiPSs) are pivotal intermediates involved in all the cathodic reactions in lithium-sulfur (Li-S) batteries. Elucidating the solvation structure of LiPSs is the first step for rational design of electrolyte and improving Li-S battery performances. Herein, we investigate the solvation structure of LiPSs and find that Li salt anions tend to enter the first solvation sheath of LiPSs and form contact ion pairs in electrolyte. The anion-involved solvation structure of LiPSs significantly influences the intrinsic kinetics of the sulfur redox reactions. In particular, the LiPS solvation structure modified by lithium bis(fluorosulfonyl)imide endows Li-S batteries with reduced polarization and enhanced rate performances under high sulfur areal loading and lean electrolyte volume conditions. This work updates the fundamental understanding of the solvation chemistry of LiPSs and highlights electrolyte engineering for promoting the performances of Li-S batteries.

11.
12.
Am J Cancer Res ; 14(1): 130-144, 2024.
Article in English | MEDLINE | ID: mdl-38323291

ABSTRACT

Circular RNAs (circRNAs) have been extensively studied for their critical roles as noncoding RNAs (ncRNAs) in gastric cancer (GC). In this study, we focused on the expression, function and molecular mechanism of circRNA_0023685 in gastric cancer (GC) to provide new ways for the diagnosis and treatment of GC. Firstly, a novel differentially expressed circRNA, circRNA_0023685, was identified, and its differential expression in GC plasma, tissue, and cell lines was further verified by RT-qPCR. Next, circRNA_0023685 was verified to promote the proliferation, migration and apoptosis of GC cells in vitro. CircRNA_0023685 was also proved to enhance the growth of GC tumors in xenograft models. Finally, for excavating the mechanism to promote GC, downstream microRNAs (miRNAs) and mRNAs were screened by bioinformatics analyses. After intersecting the target genes and genes enriched in GO analysis, a circRNA competing endogenous RNAs (ceRNAs) network was built. A protein-protein interaction (PPI) network was then constructed to find the candidate gene, APP. Our study confirmed that the highly expressed circRNA_0023685 could promote GC, which provided a new clinical diagnostic biomarker and therapeutic target for GC.

13.
Sci Data ; 11(1): 31, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38177233

ABSTRACT

Ellobium chinense is an airbreathing, pulmonate gastropod species that inhabits saltmarshes in estuaries of the northwestern Pacific. Due to a rapid population decline and their unique ecological niche in estuarine ecosystems, this species has attracted special attention regarding their conservation and the genomic basis of adaptation to frequently changing environments. Here we report a draft genome assembly of E. chinense with a total size of 949.470 Mb and a scaffold N50 of 1.465 Mb. Comparative genomic analysis revealed that the GO terms enriched among four gastropod species are related to signal transduction involved in maintaining electrochemical gradients across the cell membrane. Population genomic analysis using the MSMC model for 14 re-sequenced individuals revealed a drastic decline in Korean and Japanese populations during the last glacial period, while the southern Chinese population retained a much larger effective population size (Ne). These contrasting demographic changes might be attributed to multiple environmental factors during the glacial-interglacial cycles. This study provides valuable genomic resources for understanding adaptation and historical demographic responses to climate change.


Subject(s)
Genome , Metagenomics , Snails , Animals , Ecosystem , Genomics , Snails/genetics
14.
iScience ; 27(1): 108579, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38161420

ABSTRACT

Tissue inhibitors of metalloproteinase (TIMPs) play a pivotal role in regulating extracellular matrix (ECM) dynamics and have been extensively studied in vertebrates. However, understanding their evolution across invertebrate phyla is limited. Utilizing the high-quality Pteria penguin genome, we conducted phylogenomic orthology analyses across metazoans, revealing the emergence and distribution of the TIMP gene family. Our findings show that TIMP repertoires originated during eumetazoan radiation, experiencing independent duplication events in different clades, resulting in varied family sizes. Particularly, Pteriomorphia bivalves within Mollusca exhibited the most significant expansion and displayed the most diverse TIMP repertoires among metazoans. These expansions were attributed to multiple gene duplication events, potentially driven by the demands for functional diversification related to multiple adaptive traits, contributing to the adaptation of Pteriomorphia bivalves as stationary filter feeders. In this context, Pteriomorphia bivalves offer a promising model for studying invertebrate TIMP evolution.

15.
Am J Sports Med ; 52(2): 406-422, 2024 02.
Article in English | MEDLINE | ID: mdl-38193194

ABSTRACT

BACKGROUND: Tendons have limited regenerative potential, so healing of ruptured tendon tissue requires a prolonged period, and the prognosis is suboptimal. Although stem cell transplantation-based approaches show promise for accelerating tendon repair, the resultant therapeutic efficacy remains unsatisfactory. HYPOTHESIS: The transplantation of stem cells preassembled as 3-dimensional spheroids achieves a superior therapeutic outcome compared with the transplantation of single-cell suspensions. STUDY DESIGN: Controlled laboratory study. METHODS: Adipose-derived stem cells (ADSCs) were assembled as spheroids using a methylcellulose hydrogel system. The secretome of ADSC suspensions or spheroids was collected and utilized to treat tenocytes and macrophages to evaluate their therapeutic potential and investigate the mechanisms underlying their effects. RNA sequencing was performed to investigate the global difference in gene expression between ADSC suspensions and spheroids in an in vitro inflammatory microenvironment. For the in vivo experiment, rabbits that underwent Achilles tendon transection, followed by stump suturing, were randomly assigned to 1 of 3 groups: intratendinous injection of saline, rabbit ADSCs as conventional single-cell suspensions, or preassembled ADSC spheroids. The tendons were harvested for biomechanical testing and histological analysis at 4 weeks postoperatively. RESULTS: Our in vitro results demonstrated that the secretome of ADSCs assembled as spheroids exhibited enhanced modulatory activity in (1) tenocyte proliferation (P = .015) and migration (P = .001) by activating extracellular signal-regulated kinase (ERK) signaling and (2) the suppression of the secretion of interleukin-6 (P = .005) and interleukin-1α (P = .042) by M1 macrophages via the COX-2/PGE2/EP4 signaling axis. Gene expression profiling of cells exposed to an inflammatory milieu revealed significantly enriched terms that were associated with the immune response, cytokines, and tissue remodeling in preassembled ADSC spheroids. Ex vivo fluorescence imaging revealed that the engraftment efficiency of ADSCs in the form of spheroids was higher than that of ADSCs in single-cell suspensions (P = .003). Furthermore, the transplantation of ADSC spheroids showed superior therapeutic effects in promoting the healing of sutured stumps, as evidenced by improvements in the tensile strength (P = .019) and fiber alignment (P < .001) of the repaired tendons. CONCLUSION: The assembly of ADSCs as spheroids significantly advanced their potential to harness tenocytes and macrophages. As a proof of concept, this study clearly demonstrates the effectiveness of using ADSC spheroids to promote tendon regeneration. CLINICAL RELEVANCE: The present study lays a foundation for future clinical applications of stem cell spheroid-based therapy for the management of tendon injuries.


Subject(s)
Achilles Tendon , Tendon Injuries , Animals , Rabbits , Achilles Tendon/pathology , Tenocytes , Adipose Tissue/pathology , Tendon Injuries/surgery , Macrophages/pathology , Stem Cells/physiology , Cell Proliferation
16.
Nanotechnology ; 35(12)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38061057

ABSTRACT

In this article, a 0.7 nm thick monolayer MoS2nanosheet gate-all-around field effect transistors (NS-GAAFETs) with conformal high-κmetal gate deposition are demonstrated. The device with 40 nm channel length exhibits a high on-state current density of ~410µAµm-1with a large on/off ratio of 6 × 108at drain voltage = 1 V. The extracted contact resistance is 0.48 ± 0.1 kΩµm in monolayer MoS2NS-GAAFETs, thereby showing the channel-dominated performance with the channel length scaling from 80 to 40 nm. The successful demonstration of device performance in this work verifies the integration potential of transition metal dichalcogenides for future logic transistor applications.

17.
J Exp Biol ; 226(21)2023 11 01.
Article in English | MEDLINE | ID: mdl-37909420

ABSTRACT

How intertidal species survive their harsh environment and how best to evaluate and forecast range shifts in species distribution are two important and closely related questions for intertidal ecologists and global change biologists. Adaptive variation in responses of organisms to environmental change across all levels of biological organization - from behavior to molecular systems - is of key importance in setting distribution patterns, yet studies often neglect the interactions of diverse types of biological variation (e.g. differences in thermal optima owing to genetic and acclimation-induced effects) with environmental variation, notably at the scale of microhabitats. Intertidal species have to cope with extreme and frequently changing thermal stress, and have shown high variation in thermal sensitivities and adaptive responses at different levels of biological organization. Here, I review the physiological and biochemical adaptations of intertidal species to environmental temperature on multiple spatial and temporal scales. With fine-scale datasets for the thermal limits of individuals and for environmental temperature variation at the microhabitat scale, we can map the thermal sensitivity for each individual in different microhabitats, and then scale up the thermal sensitivity analysis to the population level and, finally, to the species level by incorporating physiological traits into species distribution models. These more refined mechanistic models that include consideration of physiological variations have higher predictive power than models that neglect these variations, and they will be crucial to answering the questions posed above concerning adaptive mechanisms and the roles they play in governing distribution patterns in a rapidly changing world.


Subject(s)
Climate Change , Ecosystem , Humans , Temperature , Phenotype
18.
Acta Haematol ; 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37926079

ABSTRACT

INTRODUCTION: Acute myeloid leukemia (AML) with internal tandem duplication (ITD) mutations in Fms-like tyrosine kinase 3 (FLT3) has an unfavorable prognosis. Recently, using newly emerging inhibitors of FLT3 has led to improved outcomes of patients with FLT3-ITD mutations. However, drug resistance and relapse continue to be significant challenges in the treatment of patients with FLT3-ITD mutations. This study aimed to evaluate the anti-leukemic effects of shikonin (SHK) and its mechanisms of action against AML cells with FLT3-ITD mutations in vitro and in vivo. METHODS: The CCK-8 assay was used to analyze cell viability, and flow cytometry was used to detect cell apoptosis and differentiation. Western blotting and real-time polymerase chain reaction (RT-PCR) were used to examine the expression of certain proteins and genes. Leukemia mouse model was created to evaluate the anti-leukemia effect of SHK against FLT3-ITD mutated leukemia in vivo. RESULTS: After screening a series of leukemia cell lines, those with FLT3-ITD mutations were found to be more sensitive to SHK in terms of proliferation inhibition and apoptosis induction than those without FLT3-ITD mutations. SHK suppresses the expression and phosphorylation of FLT3 receptors and their downstream molecules. Inhibition of the NF-κB/miR-155 pathway is an important mechanism through which SHK kills FLT3-AML cells. Moreover, a low concentration of SHK promotes the differentiation of AML cells with FLT3-ITD mutations. Finally, SHK could significantly inhibit the growth of MV4-11 cells in leukemia bearing mice. CONCLUSION: The findings of this study indicate that SHK is a promising drug for the treatment of FLT3-ITD mutated AML.

19.
iScience ; 26(12): 108376, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38034360

ABSTRACT

Rapid genetic selection is critical for allowing natural populations to adapt to different thermal environments such as those that occur across intertidal microhabitats with high degrees of thermal heterogeneity. To address the question of how thermal regimes influence selection and adaptation in the intertidal black mussel Mytilisepta virgata, we continuously recorded environmental temperatures in both tidal pools and emergent rock microhabitats and then assessed genetic differentiation, gene expression patterns, RNA editing level, and cardiac performance. Our results showed that the subpopulations in the tidal pool and on emergent rocks had different genetic structures and exhibited different physiological and molecular responses to high-temperature stress. These results indicate that environmental heterogeneity across microhabitats is important for driving genetic differentiation and shed light on the importance of post-settlement selection for adaptively modifying the genetic composition and thermal responses of these intertidal mussels.

20.
Sensors (Basel) ; 23(21)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37960410

ABSTRACT

Smart agriculture utilizes Internet of Things (IoT) technologies to enable low-cost electrical conductivity (EC) sensors to support farming intelligence. Due to aging and changes in weather and soil conditions, EC sensors are prone to long-term drift over years of operation. Therefore, regular recalibration is necessary to ensure data accuracy. In most existing solutions, an EC sensor is calibrated by using the standard sensor to build the calibration table. This paper proposes SensorTalk3, an ensemble approach of machine learning models including XGBOOST and Random Forest, which can be executed at an edge device (e.g., Raspberry Pi) without GPU acceleration. Our study indicates that the soil information (both temperature and moisture sensor data) plays an important role in SensorTalk3, which significantly outperforms the existing calibration approaches. The MAPE of SensorTalk3 can be as low as 1.738%, compared to the 7.792% error of the original sensor. Our study indicates that when the errors of uncalibrated moisture and temperature sensors are not larger than 8.3%, SensorTalk3 can accurately calibrate EC. SensorTalk3 can perform model training during data collection at the edge node. When all training data are collected, AI training is also finished at the edge node. Such an AI training approach has not been found in existing edge AI approaches. We also proposed the dual-sensor detection solution to determine when to conduct recalibration. The overhead of this solution is less than twice the optimal detection scenario (which cannot be achieved practically). If the two non-standard sensors are homogeneous and stable, then the optimal detection scenario can be approached. Conventional methods require training calibration AI models in the cloud. However, SensorTalk3 introduces a significant advancement by enabling on-site transfer learning in the edge node. Given the abundance of farming sensors deployed in the fields, performing local transfer learning using low-cost edge nodes proves to be a more cost-effective solution for farmers.

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