Tryptophan regulates sorghum root growth and enhances low nitrogen tolerance.

Over evolutionary time, plants have developed sophisticated regulatory mechanisms to adapt to fluctuating nitrogen (N) environments, ensuring that their growth is balanced with their responses to N stress. This study explored the potential of L-tryptophan (Trp) in regulating sorghum root growth under conditions of N limitation. Here, two distinct sorghum genotypes (low-N tolerance 398B and low-N sensitive CS3541) were utilized for investigating effect of low-N stress on root morphology and conducting a comparative transcriptomics analysis. Our foundings indicated that 398B exhibited longer roots, greater root dry weights, and a higher Trp content compared to CS3541 under low-N conditions. Furthermore, transcriptome analysis revealed substantial differences in gene expression profiles related to Trp pathway and carbon (C) and N metabolism pathways between the two genotypes. Additional experiments were conducted to assess the effects of exogenous Trp treatment on the interplay between sorghum root growth and low-N tolerance. Our observations showed that Trp-treated plants developed longer root and had elevated levels of Trp and IAA under low-N conditons. Concurrently, these plants demonstrated stronger physiological activities in C and N metabolism when subjected to low-N stress. These results underscored the pivotal role of Trp on root growth and low-N stress responses by balancing IAA levels and C and N metabolism. This study not only deepens our understanding of how plants maintain growth plasticity during environmental stress but also provides valuable insights into the availability of amino acid in crops, which could be instrumental in developing strategies for promoting crop resilience to N deficiency.

Integrative multi-omics analysis reveals the crucial biological pathways involved in the adaptive response to NaCl stress in peanut seedlings.

Plant growth is restricted by salt stress, which is a significant abiotic factor, particularly during the seedling stage. The aim of this study was to investigate the mechanisms underlying peanut adaptation to salt stress by transcriptomic and metabolomic analysis during the seedling stage. In this study, phenotypic variations of FH23 and NH5, two peanut varieties with contrasting tolerance to salt, changed obviously, with the strongest differences observed at 24 h. FH23 leaves wilted and the membrane system was seriously damaged. A total of 1470 metabolites were identified, with flavonoids being the most common (21.22%). Multi-omics analyses demonstrated that flavonoid biosynthesis (ko00941), isoflavones biosynthesis (ko00943), and plant hormone signal transduction (ko04075) were key metabolic pathways. The comparison of metabolites in isoflavone biosynthesis pathways of peanut varieties with different salt tolerant levels demonstrated that the accumulation of naringenin and formononetin may be the key metabolite leading to their different tolerance. Using our transcriptomic data, we identified three possible reasons for the difference in salt tolerance between the two varieties: (1) differential expression of LOC112715558 (HIDH) and LOC112709716 (HCT), (2) differential expression of LOC112719763 (PYR/PYL) and LOC112764051 (ABF) in the abscisic acid (ABA) signal transduction pathway, then (3) differential expression of genes encoding JAZ proteins (LOC112696383 and LOC112790545). Key metabolites and candidate genes related to improving the salt tolerance in peanuts were screened to promote the study of the responses of peanuts to NaCl stress and guide their genetic improvement.

miR-21 Responsive Nanocarrier Targeting Ovarian Cancer Cells.

In recent years, DNA origami-based nanocarriers have been extensively utilized for efficient cancer therapy. However, developing a nanocarrier capable of effectively protecting cargos such as RNA remains a challenge. In this study, we designed a compact and controllable DNA tubular origami (DTO) measuring 120 nm in length and 18 nm in width. The DTO exhibited appropriate structural characteristics for encapsulating and safeguarding cargo. Inside the DTO, we incorporated 20 connecting points to facilitate the delivery of cargoes to various ovarian and normal epithelial cell lines. Specifically, fluorescent-labeled DNA strands were attached to these sites as cargoes. The DTO was engineered to open upon encountering miR-21 through RNA/DNA strand displacement. Significantly, for the first time, we inhibited fluorescence using the compact DNA nanotube and observed dynamic fluorescent signals, indicating the controllable opening of DTO through live-cell imaging. Our results demonstrated that the DTO remained properly closed, exhibited effective internalization in ovarian cancer cells in vitro, showcasing marked differential expression of miR-21, and efficiently opened with short-term exposure to miR-21. Leveraging its autonomous behavior and compact design, the DTO emerges as a promising nanocarrier for various clinically relevant materials. It holds significant application prospects in anti-cancer therapy and the development of flexible biosensors.

Application of connectivity index of cubic fuzzy graphs for identification of danger zones of tsunami threat.

Fuzzy graphs are very important when we are trying to understand and study complex systems with uncertain and not exact information. Among different types of fuzzy graphs, cubic fuzzy graphs are special due to their ability to represent the membership degree of both vertices and edges using intervals and fuzzy numbers, respectively. To figure out how things are connected in cubic fuzzy graphs, we need to know about cubic α-strong, cubic ß-strong and cubic δ-weak edges. These concepts better help in making decisions, solving problems and analyzing things like transportation, social networks and communication systems. The applicability of connectivity and comprehension of cubic fuzzy graphs have urged us to discuss connectivity in the domain of cubic fuzzy graphs. In this paper, the terms partial cubic α-strong and partial cubic δ-weak edges are introduced for cubic fuzzy graphs. The bounds and exact expression of connectivity index for several cubic fuzzy graphs are estimated. The average connectivity index for cubic fuzzy graphs is also defined and some results pertaining to these concepts are proved in this paper. The results demonstrate that removing some vertices or edges may cause a change in the value of connectivity index or average connectivity index, but the change will not necessarily be related to both values. This paper also defines the concepts of partial cubic connectivity enhancing node and partial cubic connectivity reducing node and some related results are proved. Furthermore, the concepts of cubic α-strong, cubic ß- strong, cubic δ-weak edge, partial cubic α-strong and partial cubic δ-weak edges are utilized to identify areas most affected by a tsunami resulting from an earthquake. Finally, the research findings are compared with the existing methods to demonstrate their suitability and creativity.

Superelastic and superflexible cellulose aerogels for thermal insulation and oil/water separation.

Aerogels with low thermal conductivity and high adsorption capacity present a promising solution to curb water pollution caused by organic reagents as well as mitigate heat loss. Although aerogels exhibiting good adsorption capacity and thermal insulation have been reported, materials with mechanical integrity, high flexibility and shear resistance still pose a formidable task. Here, we produced bacterial cellulose-based ultralight multifunctional hybrid aerogels by using freeze-drying followed by chemical vapor deposition silylation method. The hybrid aerogels displayed a low density of 10-15 mg/cm3, high porosity exceeding 99.1 %, low thermal conductivity (27.3-29.2 mW/m.K) and superior hydrophobicity (water contact angle>120o). They also exhibited excellent mechanical properties including superelasticity, high flexibility and shear resistance. The hybrid aerogels demonstrated high heat shielding efficiency when used as an insulating material. As a selective oil absorbent, the hybrid aerogels exhibit a maximum adsorption capacity of up to approximately 156 times its own weight and excellent recoverability. Especially, the aerogel's highly accessible porous microstructure results in an impressive flux rate of up to 162 L/h.g when used as a filter in a continuous oil-water separator to isolate n-hexane-water mixtures. This work presents a novel endeavor to create high-performance, sustainable, reusable, and adaptable multifunctional aerogels.

Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.

MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) orchestrates diverse environmental signals to facilitate cell growth and is frequently activated in cancer. Translocation of MTORC1 from the cytosol to the lysosomal surface by the RRAG GTPases is the key step in MTORC1 activation. Here, we demonstrated that transcription factors MEF2A and MEF2D synergistically regulated MTORC1 activation via modulating its cyto-lysosome shutting. Mechanically, MEF2A and MEF2D controlled the transcription of FNIP1 and FNIP2, the components of the FLCN-FNIP1 or FNIP2 complex that acts as a RRAGC-RRAGD GTPase-activating element to promote the recruitment of MTORC1 to lysosome and its activation. Furthermore, we determined that the pro-oncogenic protein kinase SRC/c-Src directly phosphorylated MEF2D at three conserved tyrosine residues. The tyrosine phosphorylation enhanced MEF2D transcriptional activity and was indispensable for MTORC1 activation. Finally, both the protein and tyrosine phosphorylation levels of MEF2D are elevated in human pancreatic cancers, positively correlating with MTORC1 activity. Depletion of both MEF2A and MEF2D or expressing the unphosphorylatable MEF2D mutant suppressed tumor cell growth. Thus, our study revealed a transcriptional regulatory mechanism of MTORC1 that promoted cell anabolism and proliferation and uncovered its critical role in pancreatic cancer progression.Abbreviation: ACTB: actin beta; ChIP: chromatin immunoprecipitation; EGF: epidermal growth factor; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; FLCN: folliculin; FNIP1: folliculin interacting protein 1; FNIP2: folliculin interacting protein 2; GAP: GTPase activator protein; GEF: guanine nucleotide exchange factors; GTPase: guanosine triphosphatase; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEF2: myocyte enhancer factor 2; MEF2A: myocyte enhancer factor 2A; MEF2D: myocyte enhancer factor 2D; MEF2D-3YF: Y131F, Y333F, Y337F mutant; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; NR4A1: nuclear receptor subfamily 4 group A member 1; RPTOR: regulatory associated protein of MTOR complex 1; RHEB: Ras homolog, mTORC1 binding; RPS6KB1: ribosomal protein S6 kinase B1; RRAG: Ras related GTP binding; RT-qPCR: real time-quantitative PCR; SRC: SRC proto-oncogene, non-receptor tyrosine kinase; TMEM192: transmembrane protein 192; WT: wild-type.

Neuromodulatory effects of high-definition theta transcranial alternating current stimulation on the parietal cortex: a pilot study of healthy males.

Introduction: Transcranial alternating current stimulation (tACS) can regulate brain functions by modulating endogenous brain rhythms. Theta-band neural oscillations are associated with memory function. In particular, theta neural oscillatory power evoked in the parietal cortex is closely related to memory retrieval processes. In this study, the immediate effects of high-definition theta transcranial alternating current stimulation (HDθ-tACS) on the human left parietal cortex were investigated using short-latency afferent inhibition (SAI) and electroencephalography (EEG). Methods: Ten subjects participated in this study. We used 6-Hz HD tACS to stimulate the left parietal cortex for 15 min. SAI was calculated, and non-linear dynamic analysis of the EEG was performed to analyze neuronal function after HD θ-tACS. Results: The results showed a significant decrease in SAI (p < 0.05), while the left frontoparietal network was reinforced, leading to brain lateralization after HD θ-tACS. During performance of a memory task, F3 signals showed a significant upward trend in approximate entropy following treatment (p < 0.05). There was also a significant decrease in cross-approximate entropy in the C3-C4 and P3-P4 connections following the intervention (p < 0.05) in a resting eyes-open condition and in the memory task condition. Discussion: In conclusion, HD θ-tACS could alter cholinergic transmission and cortical excitability between the parietal and motor cortices, as well as reinforcing the frontoparietal network and the left-lateralization phenomenon, which may facilitate memory formation, encoding, and consolidation.

Clinical Research Progress of the Post-Stroke Upper Limb Motor Function Improvement via Transcutaneous Auricular Vagus Nerve Stimulation.

Stroke is a disease with high morbidity and disability, and motor impairment is a common sequela of stroke. Transcutaneous auricular vagus nerve stimulation (taVNS) is a type of non-invasive stimulation, which can effectively improve post-stroke motor dysfunction. This review discusses stimulation parameters, intervention timing, and the development of innovative devices for taVNS. We further summarize the application of taVNS in improving post-stroke upper limb motor function to further promote the clinical research and application of taVNS in the rehabilitation of post-stroke upper limb motor dysfunction.

Towards Chinese text and DNA shift encoding scheme based on biomass plasmid storage.

DNA, as the storage medium in organisms, can address the shortcomings of existing electromagnetic storage media, such as low information density, high maintenance power consumption, and short storage time. Current research on DNA storage mainly focuses on designing corresponding encoders to convert binary data into DNA base data that meets biological constraints. We have created a new Chinese character code table that enables exceptionally high information storage density for storing Chinese characters (compared to traditional UTF-8 encoding). To meet biological constraints, we have devised a DNA shift coding scheme with low algorithmic complexity, which can encode any strand of DNA even has excessively long homopolymer. The designed DNA sequence will be stored in a double-stranded plasmid of 744bp, ensuring high reliability during storage. Additionally, the plasmid's resistance to environmental interference ensuring long-term stable information storage. Moreover, it can be replicated at a lower cost.

The determination of peanut (Arachis hypogaea L.) pod-sizes during the rapid-growth stage by phytohormones.

BACKGROUND: Pod size is an important yield target trait for peanut breeding. However, the molecular mechanism underlying the determination of peanut pod size still remains unclear. RESULTS: In this study, two peanut varieties with contrasting pod sizes were used for comparison of differences on the transcriptomic and endogenous hormonal levels. Developing peanut pods were sampled at 10, 15, 20, 25 and 30 days after pegging (DAP). Our results showed that the process of peanut pod-expansion could be divided into three stages: the gradual-growth stage, the rapid-growth stage and the slow-growth stage. Cytological analysis confirmed that the faster increase of cell-number during the rapid-growth stage was the main reason for the formation of larger pod size in Lps. Transcriptomic analyses showed that the expression of key genes related to the auxin, the cytokinin (CK) and the gibberellin (GA) were mostly up-regulated during the rapid-growth stage. Meanwhile, the cell division-related differentially expressed genes (DEGs) were mostly up-regulated at 10DAP which was consistent with the cytological-observation. Additionally, the absolute quantification of phytohormones were carried out by liquid-chromatography coupled with the tandem-mass-spectrometry (LC-MS/MS), and results supported the findings from comparative transcriptomic studies. CONCLUSIONS: It was speculated that the differential expression levels of TAA1 and ARF (auxin-related), IPT and B-ARR (CK-related), KAO, GA20ox and GA3ox (GA-related), and certain cell division-related genes (gene-LOC112747313 and gene-LOC112754661) were important participating factors of the determination-mechanism of peanut pod sizes. These results were informative for the elucidation of the underlying regulatory network in peanut pod-growth and would facilitate further identification of valuable target genes.

Case report: High-frequency repetitive transcranial magnetic stimulation for treatment of hereditary spastic paraplegia type 11.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disorders that currently have no cure. HSP type 11 (SPG11-HSP) is a complex form carrying mutations in the SPG11 gene. Neuropathological studies demonstrate that motor deficits in these patients are mainly attributed to axonal degeneration of the corticospinal tract (CST). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that can induce central nervous system plasticity and promote neurological recovery by modulating the excitability of cortical neuronal cells. Although rTMS is expected to be a therapeutic tool for neurodegenerative diseases, no previous studies have applied rTMS to treat motor symptoms in SPG11-HSP. Here, we report a case of SPG11-HSP with lower extremity spasticity and gait instability, which were improved by applying high-frequency rTMS (HF-rTMS) at the primary motor cortex (M1). Clinical and physiological features were measured throughout the treatment, including the Modified Ashworth Scale (MAS), Berg Balance Scale (BBS), the timed up and go (TUG) test and the 10-meter walk test time (10 MWT). The structure and excitability of the CST were assessed by diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS), respectively. After treatment, the patient gained 17 points of BBS, along with a gradual decrease in MAS scores of the bilateral lower extremity. In addition, the TUG test and 10 MWT improved to varying degrees. TMS assessment showed increased motor evoked potential (MEP) amplitude, decreased resting motor threshold (RMT), decreased central motor conduction time (CMCT), and decreased difference in the cortical silent period (CSP) between bilateral hemispheres. Using the DTI technique, we observed increased fractional anisotropy (FA) values and decreased mean diffusivity (MD) and radial diffusivity (RD) values in the CST. It suggests that applying HF-rTMS over the bilateral leg area of M1 (M1-LEG) is beneficial for SPG11-HSP. In this study, we demonstrate the potential of rTMS to promote neurological recovery from both functional and structural perspectives. It may provide a clinical rationale for using rTMS in the rehabilitation of HSP patients.

Towards long double-stranded chains and robust DNA-based data storage using the random code system.

DNA has become a popular choice for next-generation storage media due to its high storage density and stability. As the storage medium of life's information, DNA has significant storage capacity and low-cost, low-power replication and transcription capabilities. However, utilizing long double-stranded DNA for storage can introduce unstable factors that make it difficult to meet the constraints of biological systems. To address this challenge, we have designed a highly robust coding scheme called the "random code system," inspired by the idea of fountain codes. The random code system includes the establishment of a random matrix, Gaussian preprocessing, and random equilibrium. Compared to Luby transform codes (LT codes), random code (RC) has better robustness and recovery ability of lost information. In biological experiments, we successfully stored 29,390 bits of data in 25,700 bp chains, achieving a storage density of 1.78 bits per nucleotide. These results demonstrate the potential for using long double-stranded DNA and the random code system for robust DNA-based data storage.

Computable structured aptamer for targeted treatment of ovarian cancer.

Nucleolin protein expression is higher on the ovarian cancer cell surface. AS1411, a DNA aptamer, can bind with nucleolin protein specifically. In this study, we developed HA and ST DNA tiles to assemble six AS1411 aptamers to deliver doxorubicin. In addition, to superior serum stability and drug loading, HA-6AS and ST-6AS outperformed TDN-AS in cellular uptake. HA-6AS and ST-6AS exhibited satisfactory targeted cytotoxicity and achieved resounding lysosomal escape. Moreover, when injected into nude mice subcutaneous xenograft models, HA-6AS reached the peak in tumor more quickly than ST-6AS, and better expressed the active targeting ability of AS1411. Our study suggests that designing appropriate DNA tiles to assemble different aptamers to deliver different chemotherapeutic drugs is a promising treatment for ovarian cancer.

Rapid microRNA detection method based on DNA strand displacement for ovarian cancer cells.

The current cancer detection methods are heavily dependent on the component analysis of corresponding cancer antigens. There is a lack of effective and simple clinical methods of ovarian cancer screening, which hinders the early identification for ovarian cancer and its treatment. To develop a simple and rapid method for quantitative analysis of ovarian cancer, we developed a DNA strand displacement-based method and finished the rapid detection of miR-21 in ovarian cancer cells within 5 min by a one-step isothermal reaction. The fluorescence intensity trajectory had a good linear relationship with miR-21 concentrations in the range of 100 fM-100 nM, with a lower limit of 6.05 pM. This detection method is simple, faster, and accurate. Besides, it can be applied to detect the miRNA biomarkers of other cancers by changing the preset sequences of toehold.

Investigating the thermal conductivity and flame-retardant properties of BN/MoS2/PCNF composite film containing low BN and MoS2 nanosheets loading.

Cellulose has attracted considerable attention as a potential substitute for plastics. However, the flammability and high thermal insulation properties of cellulose contradict the unique requirements for highly integrated and miniaturized electronics i.e., rapid thermal dissipation and efficient flame retardancy. In this work, cellulose was first phosphorylated to achieve intrinsic flame-retardant properties, and subsequently treated with MoS2 and BN, ensuring efficient dispersion throughout the material. Via chemical crosslinking, a sandwich-like unit was formed, in the order of BN, MoS2, and phosphorylated cellulose nanofibers (PCNF). The sandwich-like units were further self-assembled, layer-by-layer, to successfully create BN/MoS2/PCNF composite films exhibiting excellent thermal conductivity and flame retardancy, and comprised a low MoS2 and BN loading. The thermal conductivity of the BN/MoS2/PCNF composite film containing 5 wt% BN nanosheets was higher than that of neat PCNF film. The combustion characterization of BN/MoS2/PCNF composite films revealed highly desirable properties that were far more superior than the BN/MoS2/TCNF (TCNF, TEMPO-oxidized cellulose nanofibers) composite films. Moreover, the toxic volatiles that escaped from flaming BN/MoS2/PCNF composite films were significantly reduced compared to that of the BN/MoS2/TCNF composite film alternative. The thermal conductivity and flame retardancy of BN/MoS2/PCNF composite films have promising application prospects in highly integrated and eco-friendly electronics.

Effects of integrated action and sensory observation therapy based on mirror neuron and embodied cognition theory on upper limb sensorimotor function in chronic stroke: a study protocol for a randomised controlled trial.

INTRODUCTION: This study protocol aims to explore the effectiveness and neural mechanism of the integration of action observation therapy (AOT) and sensory observation therapy (SOT) for post-stroke patients on upper limb sensorimotor function. METHODS AND ANALYSIS: This is a single-centre, single-blind, randomised controlled trial. A total of 69 patients with upper extremity hemiparesis after stroke will be recruited and randomly divided into an AOT group, a combined action observation and somatosensory stimulation therapy (AOT+SST) group, and a combined AOT and SOT (AOT+SOT) group in a 1:1:1 ratio. Each group will receive 30 min of daily treatment, five times weekly for 4 weeks. The primary clinical outcome will be the Fugl-Meyer Assessment for Upper Extremity. Secondary clinical outcomes will include the Box and Blocks Test, modified Barthel Index and sensory assessment. All clinical assessments and resting-state functional MRI and diffusion tensor imaging data will be obtained at pre-intervention (T1), post-intervention (T2) and 8 weeks of follow-up (T3). ETHICS AND DISSEMINATION: The trial was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Traditional Medicine (Grant No. 2020-178). The results will be submitted to a peer-review journal or at a conference. TRIAL REGISTRATION NUMBER: ChiCTR2000040568.

DNA strand displacement based computational systems and their applications.

DNA computing has become the focus of computing research due to its excellent parallel processing capability, data storage capacity, and low energy consumption characteristics. DNA computational units can be precisely programmed through the sequence specificity and base pair principle. Then, computational units can be cascaded and integrated to form large DNA computing systems. Among them, DNA strand displacement (DSD) is the simplest but most efficient method for constructing DNA computing systems. The inputs and outputs of DSD are signal strands that can be transferred to the next unit. DSD has been used to construct logic gates, integrated circuits, artificial neural networks, etc. This review introduced the recent development of DSD-based computational systems and their applications. Some DSD-related tools and issues are also discussed.

Effects of Exogenous Auxin on Mesocotyl Elongation of Sorghum.

The length of sorghum mesocotyl plays a vital role in seed emergence from the soil, which is the foundation of healthy growth. In this study, we aimed to understand how exogenous auxin (IAA) promoted mesocotyl elongation of sorghum and its physiology mechanism. The results presented that exogenous IAA significantly promoted mesocotyl elongation in MS24B (short mesocotyl inbred line) by increasing the cell length, while with extra exogenous NPA (IAA inhibitor) application, the mesocotyl length presented a significant short phenotype. In Z210 (long mesocotyl inbred line), exogenous IAA had a slight effect on mesocotyl length elongation, while the NPA treatment decreased the mesocotyl length considerably. In MS24B, IAA treatment increased the activity of amylase to degrade starch to soluble sugar, and the activity of hexokinase was improved to consume the increased soluble sugar to offer more energy. The energy will help to increase the activity of PM H+-ATPase and the expression of expansin-related genes, which ultimately will promote the acidification of the plasma membrane in MS24B for cell elongation. Overall, the exogenous IAA functioned on the activation of energy metabolism, which in turn, inducted the acidification of the plasma membrane for mesocotyl elongation.

Neural signatures for the n-back task with different loads: An event-related potential study.

The n-back task is widely used in working memory (WM) research. However, it remains unclear how the electrophysiological correlates of WM processes, the P2, N2, P300, and negative slow wave (NSW), are affected by differences in load. Specifically, while previous work has examined the P300, less attention has been paid to the other components assessing the load of the n-back paradigm. The present study aims to investigate whether other sub-processes in WM (such as inhibitory control) are as sensitive to n-back load changes as the update process by observing changes in the above event-related potential (ERP) components. The results showed poorer behavioral performance with increasing WM load. Greater NSW and smaller P300 amplitudes were elicited by n-back task with a higher load compared to that with lower load. In contrast, there was no significant effect of the n-back load on the amplitudes of P2 and N2. These findings suggest that the updating process and the maintenance process are sensitive to the n-back load change. Therefore, changes in the updating and maintenance processes should be considered when using the n-back task to manipulate the WM load in experiments. The present study may contribute to the understanding of the complexity of WM loads. Additionally, a theoretical basis for follow-up research to explore ways of improving WM performance with high load is provided.

A novel copper chelator for the suppression of colorectal cancer.

Copper ions play a crucial role in the progression of cancers. Tumor tissue is rich in copper ions, and copper chelators could potentially scavenge these copper ions and thus exert an antitumor effect. In this study, we report the synthesis of a novel thieno[3,2-c]pyridine compound we have called "JYFY-001" that can act as the copper chelator thanks to the inclusion of an N-(pyridin-2-yl)acetamide moiety that targets copper ions. JYFY-001 potently inhibited cancer proliferation, inducing cell apoptosis and impairing the extracellular acidification rate and oxygen consumption rate of colorectal cancer (CRC) cells. JYFY-001 also inhibited the growth of a CRC-transplanted tumor in a dose-dependent manner, inducing apoptosis of the tumor cells and promoting the infiltration of lymphocytes in the CRC-transplanted tumor tissues. JYFY-001 also enhanced the antitumor effects of the programmed cell death protein 1 (PD-1) inhibitor. The relatively benign nature of JYFY-001 was demonstrated by the effect on normal cell viability and acute toxicity tests in mice. Our findings suggest that JYFY-001 is a prospective copper chelator to be used as a targeted drug and a synergist of immunotherapy for CRC treatments.