Numerical study on the stimulation effect of boundary sealing and hot water injection in marine challenging gas hydrate extraction.

This study proposed a novel development mode combining boundary sealing and hot water injection to address the challenges of gas leakage, limited reservoir sensible heat, boundary water intrusion, and low productivity faced by challenging hydrate extraction, and the stimulation effect was numerically investigated with Shenhu hydrates as the geological background. The results showed that lower boundary permeability facilitated pressure propagation and achieved volumetric dissociation of hydrates, whereas insufficient formation energy resulted in substantial gas retention. Hot water injection was effective for stimulation, but open boundaries could not maintain the high injection pressure, leading to massive hot water losses and gas escapes. However, their combination achieved a synergistic stimulation like "1 + 1 > 2" because a piston water drive similar to secondary recovery in oil and gas development was formed. Relative to three-spot well patterns, the five-spot shortened the extraction cycle by 680 days and enhanced the gas-to-water ratio by 17%. Increasing injection pressure enhanced water yield more significantly while the improvement of gas yield was more significant by increasing hot water temperature. Overall, high-pressure and high-temperature injection was suggested for gas enhancement and water control. These findings provide important guidance for advancing the commercial development of challenging hydrates.

Calib-RT: an open source python package for peptide retention time calibration in DIA mass spectrometry data.

MOTIVATION: The data independent acquisition (DIA) mass spectrometry (MS) method is increasingly popular in the field of proteomics. But the loss of the correspondence between peptide ions and their spectra in DIA makes the identification challenging. One effective approach to reduce false positive identification is to calculate the deviation between the peptide's estimated retention time (RT) and measured RT. During this process, scaling the spectral library RT into the estimated RT, known as the RT calibration, is a prerequisite for calculating the deviation. Currently, within the DIA algorithm ecosystem, there is a lack of engine-independent and readily usable RT calibration toolkits. RESULTS: In this work, we introduce Calib-RT, a RT calibration method tailored to the characteristics of RT data. This method can achieve the nonlinear calibration across various data scales and tolerate a certain level of noise interference. Calib-RT is expected to enrich the open source DIA algorithm toolchain and assist in the development of DIA identification algorithms. AVAILABILITY AND IMPLEMENTATION: Calib-RT is released as an open source software under the MIT license and can be installed from PyPi as a python module. The source code is available on GitHub at https://github.com/chenghui03/Calib_RT.

Integration of photomagnetic bimodal imaging to monitor an autogenous exosome loaded platform: unveiling strong targeted retention effects for guiding the photothermal and magnetothermal therapy in a mouse prostate cancer model.

BACKGROUND: Prostate cancer (PCa) is the most prevalent cancer among males, emphasizing the critical need for precise diagnosis and treatment to enhance patient prognosis. Recent studies have extensively utilized urine exosomes from patients with cancer for targeted delivery. This study aimed to employ highly sensitive magnetic particle imaging (MPI) and fluorescence molecular imaging (FMI) to monitor the targeted delivery of an exosome-loaded platform at the tumour site, offering insights into a potential combined photothermal and magnetic thermal therapy regime for PCa. RESULTS: MPI and FMI were utilized to monitor the in vivo retention performance of exosomes in a prostate tumour mouse model. The exosome-loaded platform exhibited robust homologous targeting ability during imaging (SPIONs@EXO-Dye:66·48%±3·85%; Dye-SPIONs: 34·57%±7·55%, **P<0·01), as verified by in vitro imaging and in vitro tissue Prussian blue staining. CONCLUSIONS: The experimental data underscore the feasibility of using MPI for in vivo PCa imaging. Furthermore, the exosome-loaded platform may contribute to the precise diagnosis and treatment of PCa.

The potential of Burkholderia gladioli KRS027 in plant growth promotion and biocontrol against Verticillium dahliae revealed by dual transcriptome of pathogen and host.

Verticillium dahliae is a destructive, soil-borne pathogen that causes significant losses on numerous important dicots. Recently, beneficial microbes inhabiting the rhizosphere have been exploited and used to control plant diseases. In the present study, Burkholderia gladioli KRS027 demonstrated excellent inhibitory effects against Verticillium wilt in cotton seedlings. Plant growth and development was promoted by affecting the biosynthesis and signaling pathways of brassinosteroids (BRs), gibberellins (GAs), and auxins, consequently promoting stem elongation, shoot apical meristem, and root apical tissue division in cotton. Furthermore, based on the host transcriptional response to V. dahliae infection, it was found that KRS027 modulates the plants to maintain cell homeostasis and respond to other pathogen stress. Moreover, KRS027 induced disruption of V. dahliae cellular structures, as evidenced by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses. Based on the comparative transcriptomic analysis between KRS027 treated and control group of V. dahliae, KRS027 induced substantial alterations in the transcriptome, particularly affecting genes encoding secreted proteins, small cysteine-rich proteins (SCRPs), and protein kinases. In addition, KRS027 suppressed the growth of different clonal lineages of V. dahliae strains through metabolites, and volatile organic compounds (VOCs) released by KRS027 inhibited melanin biosynthesis and microsclerotia development. These findings provide valuable insights into an alternative biocontrol strategy for Verticillium wilt, demonstrating that the antagonistic bacterium KRS027 holds promise as a biocontrol agent for promoting plant growth and managing disease occurrence.

A mechanistic investigation into combined influences of NaCl and extrusion temperature on fibrous structures of high-moisture textured yeast protein.

NaCl and extrusion temperature have an important influence on the qualities of high-moisture textured proteins, but the influence mechanism is still unclear. Therefore, this study prepared high-moisture textured yeast protein (HMTYP) with different NaCl contents (0%-4%) under different extrusion temperatures (170 °C, 180 °C) and characterized their physicochemical properties. The results showed that the HMTYP containing 1% and 2% NaCl prepared at 180 °C contained a strong fibrous structure. The possible mechanism was as follows: YP could not be sufficiently melted at 170 °C after adding NaCl, causing a decrease in the structural strength; however, at 180 °C, YP still reached a fully molten state even though 1%-2% NaCl was added. After YP sufficiently melted, NaCl enhanced the cross-linking and aggregation of proteins during cooling, which improved the textural properties of HMTYP. Accordingly, NaCl and extrusion temperature could combine to adjust the fibrous structure and texture of HMTYP.

Improving diagnostic confidence in low-dose dual-energy CTE with low energy level and deep learning reconstruction.

OBJECTIVE: To demonstrate the value of using 50 keV virtual monochromatic images with deep learning image reconstruction (DLIR) in low-dose dual-energy CT enterography (CTE). METHODS: In this prospective study, 114 participants (62 % M; 41.9 ± 16 years) underwent dual-energy CTE. The early-enteric phase was performed using standard-dose (noise index (NI): 8) and images were reconstructed at 70 keV and 50 keV with 40 % strength ASIR-V (ASIR-V40%). The late-enteric phase used low-dose (NI: 12) and images were reconstructed at 50 keV with ASIR-V40%, and DLIR at medium (DLIR-M) and high strength (DLIR-H). Image standard deviation (SD), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), edge-rise-slope (ERS) were computed. The quantitative comb sign score was calculated for the 27 patients with Crohn's disease. The subjective noise, image contrast, display of rectus artery were scored using a 5-point scale by two radiologists blindly. RESULTS: Effective dose was reduced by 50 % (P < 0.001) in the late-enteric phase to 3.26 mSv. The lower-dose 50 keV-DLIR-H images (SD:17.7 ± 0.5HU) had similar image noise (P = 0.97) as the standard-dose 70 keV-ASIR-V40% images (SD:17.7 ± 0.73HU), but with higher (P < 0.001) SNR, CNR, ERS and quantitative comb sign score (5.7 ± 0.17, 1.8 ± 0.12, 156.04 ± 5.21 and 5.05 ± 0.73, respectively). Furthermore, the lower-dose 50 keV-DLIR-H images obtained the highest score in the rectus artery visibility (4.27 ± 0.6). CONCLUSIONS: The 50 keV images in dual-energy CTE with DLIR provides high-quality images, with a 50 % reduction in radiation dose. Images with high contrast and density resolutions significantly enhance the diagnostic confidence of Crohn's disease and are essential for the clinical development of individualized treatment plans.

Effects of socioeconomic status and regional inequality on the association between PM2.5 and its components and cardiometabolic multimorbidity: A multicenter population-based survey in eastern China.

BACKGROUND: Despite evidence linking fine particulate matter (PM2.5) to cardiometabolic multimorbidity (CMM), the impact of its components remains unclear. Socioeconomic status (SES) and regional disparities may confound their association. We aim to evaluate the associations between PM2.5 components and CMM and explore how socioeconomic status and regional disparities affect these relationships. METHODS: We recruited 108,941 participants aged 35-76 years from ten cities in eastern China. Individual exposure was assessed using Tracking Air Pollution in China (TAP) data, including PM2.5 and five components: ammonium (NH4+), black carbon (BC), nitrates (NO3-), organic matter (OM), and sulfates (SO42-). Generalized linear models and quantile g-computation models were employed to quantify the effects of PM2.5 components on CMM and to identify key components. Stratified analyses were performed to investigate the modifying effect of SES and regional disparities. RESULTS: For each increase in interquartile range (IQR), BC (odds ratio [OR] 1.37, 95 % CI 1.29-1.47), OM (1.38, 1.29-1.48), NH4+ (1.31, 1.21-1.40), NO3- (1.34, 1.25-1.44), and SO42- (1.28, 1.20-1.38) were positively associated with CMM. Joint exposure to five components was significantly positively associated with CMM (OR: 1.27, 95 % CI: 1.21-1.33), with SO42- having the highest estimated weight, followed by NO3- and BC. These associations were stronger for participants from low socio-economic status and poor regions. CONCLUSION: In summary, we found a stronger hazard effect of PM2.5 and its components on CMM, compared to those suffering from CMDs, particularly among participants with low socioeconomic status and in poor regions. SO42- may be a primary contributor to the association between PM2.5 components and CMM. These findings underscore the importance of prioritizing CMM and targeting SO42-related pollution sources in health policies, particularly amid China's aging population, reducing environmental health inequalities is critical.

Targeting focal adhesion kinase (FAK) in cancer therapy: A recent update on inhibitors and PROTAC degraders.

Focal adhesion kinase (FAK) is considered as a pivotal intracellular non-receptor tyrosine kinase, and has garnered significant attention as a promising target for anticancer drug development. As of early 2024, a total of 12 drugs targeting FAK have been approved for clinical or preclinical studies worldwide, including three PROTAC degraders. In recent three years (2021-2023), significant progress has been made in designing targeted FAK anticancer agents, including the development of a novel benzenesulfofurazan type NO-releasing FAK inhibitor and the first-in-class dual-target inhibitors simultaneously targeting FAK and HDACs. Given the pivotal role of FAK in the discovery of anticancer drugs, as well as the notable advancements achieved in FAK inhibitors and PROTAC degraders in recent years, this review is underbaked to present a comprehensive overview of the function and structure of FAK. Additionally, the latest findings on the inhibitors and PROTAC degraders of FAK from the past three years, along with their optimization strategies and anticancer activities, were summarized, which might help to provide novel insights for the development of novel targeted FAK agents with promising anticancer potential and favorable pharmacological profiles.

Genetic Analysis and Fine Mapping of a New Rice Mutant, Leaf Tip Senescence 2.

Premature leaf senescence significantly reduces rice yields. Despite identifying numerous factors influencing these processes, the intricate genetic regulatory networks governing leaf senescence demand further exploration. We report the characterization of a stably inherited, ethyl methanesulfonate(EMS)-induced rice mutant with wilted leaf tips from seedling till harvesting, designated lts2. This mutant exhibits dwarfism and early senescence at the leaf tips and margins from the seedling stage when compared to the wild type. Furthermore, lts2 displays a substantial decline in both photosynthetic activity and chlorophyll content. Transmission electron microscopy revealed the presence of numerous osmiophilic granules in chloroplast cells near the senescent leaf tips, indicative of advanced cellular senescence. There was also a significant accumulation of H2O2, alongside the up-regulation of senescence-associated genes within the leaf tissues. Genetic mapping situated lts2 between SSR markers Q1 and L12, covering a physical distance of approximately 212 kb in chr.1. No similar genes controlling a premature senescence leaf phenotype have been identified in the region, and subsequent DNA and bulk segregant analysis (BSA) sequencing analyses only identified a single nucleotide substitution (C-T) in the exon of LOC_Os01g35860. These findings position the lts2 mutant as a valuable genetic model for elucidating chlorophyll metabolism and for further functional analysis of the gene in rice.

Endoplasmic reticulum stress regulates apoptosis and chemotherapeutic via enhancing TNFRSF10B recycling to the cell membrane in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most common malignant tumor in China. The expression and cell surface levels of TNF receptor superfamily member 10B (TNFRSF10B) are associated with apoptosis and chemotherapy. However, the precise molecular mechanisms that govern the regulation of TNFRSF10B remain unclear. MATERIALS AND METHODS: RNA-Seq data related to TNBC chemotherapy resistance were acquired from the GEO database. The mRNA and protein levels of TNFRSF10B were detected using RT-PCR and Western blotting, respectively. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect cell proliferation. Annexin V/7-AAD staining was used to evaluate apoptosis. The cell membrane TNFRSF10B was analyzed by Western blotting and immunofluorescence. Inducers and inhibitors of endoplasmic reticulum stress (ERS) were used to assess the effect of ERS on TNFRSF10B localization. RESULTS: TNFRSF10B expression was downregulated in TNBC and was associated with prognosis. TNFRSF10B overexpression inhibits the growth of TNBC both in vivo and in vitro and can partially counteract chemotherapy resistance. ERS activation in TNBC promotes the expression of TNFRSF10B, leading to its enrichment on the cell membrane surface, thereby activating the apoptotic pathways. CONCLUSION: ERS regulates the expression and subcellular localization of TNFRSF10B in TNBC cells. They synergistically affect anti-apoptosis and chemotherapy resistance in TNBC cells.

Identification of Angiogenesis-Related Genes and Molecular Subtypes for Psoriasis Based on Random Forest Algorithm.

Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithms. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis (PCA). A diagnostic model was developed using random forest algorithm (ntree=400) and validated by ROC curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by qRT-PCR. We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P<0.0001) and interleukins pathway (R=0.79, P<0.0001). Furtherer, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes.

Impaired thyroid hormone sensitivity exacerbates the effect of PM2.5 and its components on dyslipidemia in schizophrenia.

BACKGROUND: Dyslipidemia in schizophrenia causes a serious loss of healthy life expectancy, making it imperative to explore key environmental risk factors. We aimed to assess the effect of PM2.5 and its constituents on dyslipidemia in schizophrenia, identify the critical hazardous components, and investigate the role of impaired thyroid hormones (THs) sensitivity in this association. METHODS: We collected disease data on schizophrenia from the Anhui Mental Health Center from 2019 to 2022. Logistic regression was constructed to explore the effect of average annual exposure to PM2.5 and its components [black carbon (BC), organic matter (OM), sulfate (SO42-), ammonium (NH4+), and nitrate (NO3-)] on dyslipidemia, with subgroup analyses for age and gender. The degree of impaired THs sensitivity in participants was reflected by the Thyroid Feedback Quantile-based Index (TFQI), and its role in the association of PM2.5 components with dyslipidemia was explored. RESULTS: A total of 5125 patients with schizophrenia were included in this study. Exposure to PM2.5 and its components (BC, OM, SO42-, NH4+, and NO3-) were associated with dyslipidemia with the odds ratios and 95 % confidence interval of 1.13 (1.04, 1.23), 1.16 (1.07, 1.26), 1.15 (1.06, 1.25), 1.11 (1.03, 1.20), 1.09 (1.00, 1.18), 1.12 (1.04, 1.20), respectively. Mixed exposure modeling indicated that BC played a major role in the effects of the mixture. More significant associations were observed in males and groups <45 years. In addition, we found that the effect of PM2.5 and its components on dyslipidemia was exacerbated as impaired THs sensitivity in the patients. CONCLUSIONS: Exposure to PM2.5 and its components is associated with an increased risk of dyslipidemia in schizophrenia, which may be exacerbated by impaired THs sensitivity. Our results suggest a new perspective for the management of ambient particulate pollution and the protection of thyroid function in schizophrenia.

The changes of intestinal microbiota and metabolomics during the inhibition of bladder cancer by liquiritigenin.

Liquiritigenin is a natural medicine. However, its inhibitory effect and its potential mechanism on bladder cancer (BCa) remain to be explored. It was found that it could be visualized that the transplanted tumours in the low-dose liquiritigenin -treated group and the high-dose liquiritigenin -treated group were smaller than those in the model group. Liquiritigenin treatment led to alterations in Lachnoclostridium, Escherichia-Shigella, Alistipes and Akkermansia. Non-targeted metabolomics analysis showed that a total of multiple differential metabolites were identified between the model group and the high-dose liquiritigenin-treated group. This provides a new direction and rationale for the antitumour effects of liquiritigenin.

Radio-Frequency Conductivity Characteristics and Corresponding Mechanism of Graphene/Copper Multilayer Structures.

High-radio-frequency (RF) conductivity is required in advanced electronic materials to reduce the electromagnetic loss and power dissipation of electronic devices. Graphene/copper (Gr/Cu) multilayers possess higher conductivity than silver under direct current conditions. However, their RF conductivity and detailed mechanisms have rarely been evaluated at the micro scale. In this work, the RF conductivity of copper-copper (P-Cu), monolayer-graphene/copper (S-Gr/Cu), and multilayer-graphene/copper (M-Gr/Cu) multilayer structures were evaluated using scanning microwave impedance microscopy (SMIM) and dielectric resonator technique. The results indicated that the order of RF conductivity was M-Gr/Cu < P-Cu < S-Gr/Cu at 3 GHz, contrasting with P-Cu < M-Gr/Cu < S-Gr/Cu at DC condition. Meanwhile, the same trend of M-Gr/Cu < P-Cu < S-Gr/Cu was also observed using the dielectric resonator technique. Based on the conductivity-related Drude model and scattering theory, we believe that the microwave radiation can induce a thermal effect at S-Gr/Cu interfaces, leading to an increasing carrier concentration in S-Gr. In contrast, the intrinsic defects in M-Gr introduce additional carrier scattering, thereby reducing the RF conductivity in M-Gr/Cu. Our research offers a practical foundation for investigating conductive materials under RF conditions.

BIGH3 mediates apoptosis and gap junction failure in osteocytes during renal cell carcinoma bone metastasis progression.

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens and in a preclinical mouse model. We also demonstrate that BIGH3 reduces Cx43 expression, blocking gap junction (GJ) function and osteocyte network communication. BIGH3-mediated GJ inhibition is blocked by the lysosomal inhibitor hydroxychloroquine (HCQ), but not osteoanabolic agents. Our results broaden the understanding of pathologic osteolysis in RCCBM and indicate that targeting the BIGH3 mechanism could be a combinational strategy for the treatment of RCCBM-induced bone disease that overcomes the limited efficacy of antiresorptives that target osteoclasts.

Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence.

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy owing to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from patients with AD. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and ROS production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

Sirtuin-6 knockout causes exacerbated stalled healing of diabetic ulcers in mice.

BACKGROUND: Diabetic ulcers (DUs) are characterized by chronic inflammation and delayed re-epithelialization, with a high incidence and weighty economic burden. The primary therapeutic strategies for refractory wounds include surgery, non-invasive wound therapy, and drugs, while the optimum regimen remains controversial. Sirtuin-6 (SIRT6) is a histone deacetylase and a key epigenetic factor that exerts anti-inflammatory and pro-proliferatory effects in wound healing. However, the exact function of SIRT6 in DUs remains unclear. METHODS: We generated tamoxifen-inducible SIRT6 knockout mice by crossing SIRT6flox/flox homozygous mice with UBC-creERT2+ transgenic mice. Systemic SIRT6 null mice, under either normal or diabetic conditions, were utilized to assess the effects of SIRT6 in DUs treatment. Gene and protein expressions of SIRT6 and inflammatory cytokines were measured by Western blotting and RT-qPCR. Histopathological examination confirmed the altered re-epithelialization (PCNA), inflammation (NF-κB p50 and F4/80), and angiogenesis (CD31) markers during DUs restoration. RESULTS: Knockout of SIRT6 inhibited the healing ability of DUs, presenting attenuated re-epithelialization (PCNA), exacerbated inflammation responses (NF-κB p50, F4/80, Il-1ß, Tnf-α, Il-6, Il-10, and Il-4), and hyperplasia vascular (CD31) compared with control mice. CONCLUSIONS: SIRT6 could boost impaired wound healing through improving epidermal proliferation, inflammation, and angiogenesis. Our study highlighted the therapeutic potential of the SIRT6 agonist for DUs treatment.

Synthesis and biological evaluation of 4-phenyl-5-quinolinyl substituted isoxazole analogues as potent cytotoxic and tubulin polymerization inhibitors against ESCC.

The identification of chemically different inhibitors that target the colchicine site of tubulin is still of great value for cancer treatment. Combretastatin A-4(CA-4), a naturally occurring colchicine-site binder characterized by its structural simplicity and biological activity, has served as a structural blueprint for the development of novel analogues with improved safety and therapeutic efficacy. In this study, a library of forty-eight 4-phenyl-5-quinolinyl substituted triazole, pyrazole or isoxazole analouges of CA-4, were synthesized and evaluated for their cytotoxicity against Esophageal Squamous Cell Carcinoma (ESCC) cell lines. Compound C11, which features a 2-methyl substitution at the quinoline and carries an isoxazole ring, emerged as the most promising, with 48 h IC50s of less than 20 nmol/L against two ESCC cell lines. The findings from EBI competitive assay, CETA, and in vitro tubulin polymerization assay of C11 are consistent with those of the positive control colchicine, demonstrating the clear affinity of compound C11 to the colchicine binding site. The subsequent cellular-based mechanism studies revealed that C11 significantly inhibited ESCC cell proliferation, arrested cell cycle at the M phase, induced apoptosis, and impeded migration. Experiments conducted in vivo further confirmed that C11 effectively suppressed the growth of ESCC without showing any toxicity towards the selected animal species. Overall, our research suggests that the tubulin polymerization inhibitor incorporating quinoline and the isoxazole ring may deserve consideration for cancer therapy.

QTL mapping and genomic selection of stem and branch diameter in soybean (Glycine max L.).

Introduction: Soybean stem diameter (SD) and branch diameter (BD) are closely related traits, and genetic clarification of SD and BD is crucial for soybean breeding. Methods: SD and BD were genetically analyzed by a population of 363 RIL derived from the cross between Zhongdou41 (ZD41) and ZYD02878 using restricted two-stage multi-locus genome-wide association, inclusive composite interval mapping, and three-variance component multi-locus random SNP effect mixed linear modeling. Then candidate genes of major QTLs were selected and genetic selection model of SD and BD were constructed respectively. Results and discussion: The results showed that SD and BD were significantly correlated (r = 0.74, P < 0.001). A total of 93 and 84 unique quantitative trait loci (QTL) were detected for SD and BD, respectively by three different methods. There were two and ten major QTLs for SD and BD, respectively, with phenotypic variance explained (PVE) by more than 10%. Within these loci, seven genes involved in the regulation of phytohormones (IAA and GA) and cell proliferation and showing extensive expression of shoot apical meristematic genes were selected as candidate genes. Genomic selection (GS) analysis showed that the trait-associated markers identified in this study reached 0.47-0.73 in terms of prediction accuracy, which was enhanced by 6.56-23.69% compared with genome-wide markers. These results clarify the genetic basis of SD and BD, which laid solid foundation in regulation gene cloning, and GS models constructed could be potentially applied in future breeding programs.

Hardware implementation of a mirror array-based optical intelligent reflecting surface for VLC: prototype and experimental results.

Faced with growing demands for high-speed and reliable communication systems, optical intelligent reflecting surfaces (OIRS) have recently attracted a lot of interest in visible light communication (VLC). With potential applications in a variety of scenarios, including indoor wireless communications and the Internet of Things (IoT), OIRS is expected to have a transformative impact on optical wireless communications. However, current research is predominantly theoretical, and the hardware implementation of OIRS is insufficient. Therefore, this paper introduces an OIRS prototype based on a mirror array, which is capable of adjusting the reflected lightwave by manipulating the orientation of individual OIRS units to realize an adjustable optical wireless communication environment. Additionally, a hardware platform with a configurable control system for OIRS-based VLC has been developed in this paper. Finally, experimental results demonstrate significant improvements in the amplitude of the received signal and the signal-to-noise ratio of the developed prototype, thereby verifying the enhancement of communication efficiency and the potential of practical OIRS deployment.