Stem cell dynamics and cellular heterogeneity across lineage subtypes of castrate resistant prostate cancer.

To resist lineage-dependent therapies such as androgen receptor inhibition, prostate luminal epithelial adenocarcinoma cells often adopt a stem-like state resulting in lineage-plasticity and phenotypic heterogeneity. Castrate resistant prostate adenocarcinoma can transition to neuroendocrine and occasionally to amphicrine, co-expressed luminal and neuroendocrine, phenotypes. We developed CRPC patient-derived organoid models that preserve heterogeneity of the originating tumor, including an amphicrine model displaying a range of luminal and neuroendocrine phenotypes. To gain biological insight and to identify potential treatment targets within heterogeneous tumor cell populations, we assessed the lineage hierarchy and molecular characteristics of various CRPC tumor subpopulations. Transcriptionally similar stem/progenitor cells were identified for all lineage populations. Lineage tracing in amphicrine CRPC showed that heterogeneity originated from distinct subclones of infrequent stem/progenitor cells that produced mainly quiescent differentiated amphicrine progeny. By contrast, adenocarcinoma CRPC progeny originated from stem/progenitor cells and self-renewing differentiated luminal cells. NEPC was composed almost exclusively of self-renewing stem/progenitor cells. Amphicrine subpopulations were enriched for secretory luminal, mesenchymal, and enzalutamide treatment persistent signatures that characterize clinical progression. Finally, the amphicrine stem/progenitor subpopulation was specifically depleted with an AURKA inhibitor, which blocked tumor growth. These data illuminate distinct stem cell characteristics for subtype-specific CRPC in addition to demonstrating a context for targeting differentiation-competent prostate stem cells.

In-orbit dark count rate performance and radiation damage high-temperature annealing of silicon avalanche photodiode single-photon detectors of the Micius satellite.

Silicon avalanche photodiode (APD) single-photon detectors in space are continuously affected by radiation, which gradually degrades their dark count performance. From August 2016 to June 2023, we conducted approximately seven years (2507 days) of in-orbit monitoring of the dark count performance of APD single-photon detectors on the Micius Quantum Science Experimental Satellite. The results showed that due to radiation effects, the dark count growth rate was approximately 6.79 cps/day @ -24 °C and 0.37 cps/day @ -55 °C, with a significant suppression effect on radiation-induced dark counts at lower operating temperature. Based on the proposed radiation damage induced dark count annealing model, simulations were conducted for the in-orbit dark counts of the detector, the simulation results are consistent with in-orbit test data. In May 2022, four of these detectors underwent a cumulative 5.7 hours high-temperature annealing test at 76 °C, dark count rate shows no measurable changes, consistent with annealing model. As of now, these ten APD single-photon detectors on the Micius Quantum Science Experimental Satellite have been in operation for approximately 2507 days and are still functioning properly, providing valuable experience for the future long-term space applications of silicon APD single-photon detectors.

Time transfer over 113†km free space laser communication channel.

The space time frequency transfer plays a crucial role in applications such as space optical clock networks, navigation, satellite ranging, and space quantum communication. Here, we propose a high-precision space time frequency transfer and time synchronization scheme based on a simple intensity modulation/direct detection (IM/DD) laser communication system, which occupies a communication bandwidth of approximately 0.2%. Furthermore, utilizing an optical-frequency comb time frequency transfer system as an out-of-loop reference, experimental verification was conducted on a 113 km horizontal atmospheric link, with a long-term stability approximately 8.3 × 10-16 over a duration of 7800 seconds. Over an 11-hour period, the peak-to-peak wander is approximately 100 ps. Our work establishes the foundation of the time frequency transfer, based on the space laser communication channel, for future ground-to-space and inter-satellite links.

The monitoring requests on young driver's fatigue and take-over performance in prolonged conditional automated driving.

INTRODUCTION: L3 automated vehicles can perform all dynamic driving tasks unless a take-over occurs due to operational limits. This issue is potentially important for young drivers who are vulnerable road users since they have skill deficits and easily evolve into aberrant driving. However, drivers lacking active involvement may be fatigued and drowsy. Previous research indicated that performing a voluntary non-driving-related task (NDRT) could keep drivers alert, but there was no difference in take-over performance with or without NDRT. Providing a monitoring request (MR) before a possible take-over request (TOR) exhibited better take-over performance in temporary automated driving. Therefore, the study aimed to investigate the effects of MR and voluntary NDRT on young drivers' fatigue and performance. METHOD: Twenty-five young drivers experienced 60 min automated driving on a highway with low traffic density and a TOR prompted due to a collision event. A within-subjects was designed that comprised three conditions: NONE, TOR-only, and MR + TOR. Drivers were allowed to perform a self-paced phone NDRT during automated driving. RESULTS: The PERCLOS and blink frequency data showed that playing phones could keep drivers vigilant. The take-over performance on whether taking phone had no difference, but with MRs condition exhibited better take-over performance including the shorter reaction time and the longer TTC. Subjective evaluations also showed the advantages of MRs with more safety, trust, acceptance, and lower workload. CONCLUSIONS: Taking MRs had a positive effect on relieving fatigue and improving take-over performance. Furthermore, MRs could potentially improve the safety and acceptance of automated driving. PRACTICAL APPLICATIONS: The MR design can be used in the automotive industry to ensure the safest interfaces between fatigue drivers and automation systems.

Prediction of cervical lymph node metastasis in solitary papillary thyroid carcinoma based on ultrasound radiomics analysis.

Objective: To assess the utility of predictive models using ultrasound radiomic features to predict cervical lymph node metastasis (CLNM) in solitary papillary thyroid carcinoma (PTC) patients. Methods: A total of 570 PTC patients were included (456 patients in the training set and 114 in the testing set). Pyradiomics was employed to extract radiomic features from preoperative ultrasound images. After dimensionality reduction and meticulous selection, we developed radiomics models using various machine learning algorithms. Univariate and multivariate logistic regressions were conducted to identify independent risk factors for CLNM. We established clinical models using these risk factors. Finally, we integrated radiomic and clinical models to create a combined nomogram. We plotted ROC curves to assess diagnostic performance and used calibration curves to evaluate alignment between predicted and observed probabilities. Results: A total of 1561 radiomics features were extracted from preoperative ultrasound images. After dimensionality reduction and feature selection, 16 radiomics features were identified. Among radiomics models, the logistic regression (LR) model exhibited higher predictive efficiency. Univariate and multivariate logistic regression results revealed that patient age, tumor size, gender, suspicious cervical lymph node metastasis, and capsule contact were independent predictors of CLNM (all P < 0.05). By constructing a clinical model, the LR model demonstrated favorable diagnostic performance. The combined model showed superior diagnostic efficacy, with an AUC of 0.758 (95% CI: 0.712-0.803) in the training set and 0.759 (95% CI: 0.669-0.849) in the testing set. In the training dataset, the AUC value of the nomogram was higher than that of the clinical and radiomics models (P = 0.027 and 0.002, respectively). In the testing dataset, the AUC value of the nomogram model was also greater than that of the radiomics models (P = 0.012). However, there was no significant statistical difference between the nomogram and the clinical model (P = 0.928). The calibration curve indicated a good fit of the combined model. Conclusion: Ultrasound radiomics technology offers a quantitative and objective method for predicting CLNM in PTC patients. Nonetheless, the clinical indicators persists as irreplaceable.

DDX5 inhibits inflammation by modulating m6A levels of TLR2/4 transcripts during bacterial infection.

DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.

Factors influencing work engagement among male nurses: A structural equation model.

AIM: To investigate the male nurses' engagement in nursing work and the influencing factors. DESIGN: A cross-sectional study. METHODS: A cross-sectional survey was conducted in 13 hospitals in China to collect data from 328 male nurses from August to October 2021. A structural equation model design was tested with validated measurement instruments. RESULTS: The work engagement of male nurses in China was at a medium level. There was a high correlation of the male nurses' work engagement with career identity (r = 0.764, p < 0.01), career success (r = 0.735, p < 0.01) and social support (r = 0.477, p < 0.01). The linear multivariate regression analysis showed that career satisfaction (ß = 0.393), career identity (ß = 0.392) and subjective support (ß = 0.116) entered regression equation of male nurses' work engagement (all p < 0.05). The structural equation model results showed that career identity and social support were the influencing factors of the male nurses' work engagement and the model explained variation of 66.4% variables. CONCLUSION: To know the male nurses' work engagement and influencing factors in China has certain enlightening significance for male nurses themselves and nursing manager. On the one hand, it is necessary to enhance the male nurses' career recognition to nursing work. On the other hand, the society should provide more aid and support to the male nurses. Therefore, the male nurses could devote more into nursing work and promote the nursing development.

Irrigation scheduling for potatoes (Solanum tuberosum L.) under drip irrigation in an arid region using AquaCrop model.

Potato is one of the key food crops and China is the largest potato producer in the world. However water scarcity is the major constraint to increase the productivity of potato in the arid regions such as Ningxia in northwest China where this crop is extensively cultivated. The overall objective of this study was to optimize the irrigation for potato cultivated under the drip irrigation. To do this, the AquaCrop model was calibrated and validated using the data obtained from two years of field experiment. Then, the calibrated crop model was used to simulate growth and tuber yield of potato in response to 30 different irrigation schemes under two different irrigation scenarios. The crop model evaluation parameters namely, the root mean square error (RMSE), the index of agreement (d), the normalized root mean square error (NRMSE) and the coefficient of determination (R2) showed that the AquaCrop model could simulate the growth and yield of potato under the drip irrigation with different irrigation treatments with reasonable accuracy. Furthermore, yield of potato has increased with increasing amount of total irrigation under drip irrigation; however, yield begins to decline when the amount of total irrigation exceeds 2500 m3 ha-1. The study also found that the optimum irrigation schedule for potato was 20 mm of irrigation quota at 7 days of irrigation cycle (i.e., 1800 m3 ha-1 or 180 mm of total irrigation). The above irrigation scheduling has achieved 46.77 t ha-1 of tuber yield with 15.74 kg m-3 of water use efficiency. These findings may be evaluated in potato cultivation across different climate and soil conditions for wide applicability at different arid regions of the world.

Free-Space and Fiber-Integrated Measurement-Device-Independent Quantum Key Distribution under High Background Noise.

Measurement-device-independent quantum key distribution (MDI QKD) provides immunity against all attacks targeting measurement devices. It is essential to implement MDI QKD in the future global-scale quantum communication network. Toward this goal, we demonstrate a robust MDI QKD fully covering daytime, overcoming the high background noise that prevents BB84 protocol even when using a perfect single-photon source. Based on this, we establish a hybrid quantum communication network that integrates free-space and fiber channels through Hong-Ou-Mandle (HOM) interference. Additionally, we investigate the feasibility of implementing HOM interference with moving satellites. Our results serve as a significant cornerstone for future integrated space-ground quantum communication networks that incorporate measurement-device-independent security.

Complete chloroplast genome and phylogenetic analysis of Smallanthus sonchifolius (Asteraceae).

Smallanthus sonchifolius (Asteraceae), is an important food plant in the world. There is no systematic report on the chloroplast genome of S. sonchifolius. Here we reported its complete chloroplast genome and analyzed the basic characteristics. The chloroplast genome was 152,301 bp in length, had a GC content of 37.55%, and encoded 113 unique genes, including 79 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. Phylogenetic analysis showed that the tribe Millerieae and the tribe Madieae are closely related in the Asteraceae family. In the tribe Millerieae, Smallanthus was more closely related to Guizotia and Sigesbeckia. This chloroplast genome not only enriches the genome information of Smallanthus, but also lays the foundation for understanding the phylogeny within the genus Smallanthus.

Water and Nitrogen Coupling on the Regulation of Soil Nutrient-Microbial Biomass Balance and Its Effect on the Yield of Wolfberry (Lycium barbarum L.).

Due to the problems of relatively fragile stability, the quality of soil in the drip-irrigated agricultural ecosystem has high spatial heterogeneity and experiences significant degradation. We conducted a two-year field plot study (2021-2022) in a typical region of the arid zone with the "wolfberry" crop as the research object, with three irrigation and three nitrogen application levels, and the local conventional management as the control (CK). Soil quality under experimental conditioning was comprehensively evaluated based on Principal Component Analysis (PCA) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), and regression analyses were carried out between the soil quality evaluation results and wolfberry yield. The results showed that short-term water and nitrogen regulation enhanced the soil nutrient content in the root zone of wolfberry to some extent, but it did not significantly affect soil carbon:soil nitrogen (Csoil:Nsoil), soil carbon:soil phosphorus (Csoil:Psoil), and soil nitrogen:soil phosphorus (Nsoil:Psoil). When the irrigation quota was increased from I1 to I2, the soil microbial biomass carbon, nitrogen, and phosphorus (Cmic, Nmic, and Pmic) tended to increase with the increase in N application, but the microbial biomass carbon:nitrogen (Cmic:Nmic), microbial biomass carbon:phosphorus (Cmic:Pmic), and microbial biomass nitrogen:phosphorus (Nmic:Pmic) did not change significantly. The comprehensive evaluation of the principal components and TOPSIS showed that the combined soil nutrient-microbial biomass and its ecological stoichiometry characteristics were better under the coupled treatments of I2, I3, N2, and N3, and the overall soil quality under these treatment conditions was significantly better than that under the CK treatment. Under I1 irrigation, nitrogen application significantly increased the yield of wolfberry, while under I2 and I3 irrigation, the wolfberry yield showed a parabolic trend with the increase in nitrogen application. The highest yield was recorded in the I2N2 treatment in the first and second years, with yields of 9967 kg hm-2 and 10,604 kg hm-2, respectively. The coefficient of determination (explained quantity) of the soil quality based on soil nutrient-microbial biomass and the characteristics of its ecological stoichiometry for wolfberry yield ranged from 0.295 to 0.573. These findings indicated a limited positive effect of these indicators of soil on wolfberry yield. The short-term water and nitrogen regulation partly influenced the soil and soil microbial biomass in agroecosystems, but the effect on elemental balance was not significant. Our findings might provide theoretical support for managing the health of agricultural ecosystems.

[Evaluation of the clinical effect of acupuncture in treatment of neck pain in cervical spondylosis based on propensity score matching].

OBJECTIVE: To observe the clinical effect and safety of acupuncture in treatment of neck pain due to cervical spondylosis. METHODS: According to the patients' preference and acceptance for the interventions of neck pain induced by cervical spondylosis, an acupuncture group (221 cases) and a non-acupuncture group (251 cases) were divided. After the control of confounding factors with propensity score matching, 218 cases were included in either acupuncture group or non-acupuncture group. In the acupuncture group, acupuncture was applied to Dazhui (GV 14), Baihui (GV 20), ashi points, bilateral neck-Jiaji (EX-B 2), Fengchi (GB 20), Houxi (SI 3), Shenmai (BL 62), etc. The treatment was given once daily, one course of intervention was composed of 5 treatments and 3 courses were included. In the non-acupuncture group, the oral administration of imrecoxib tablets and cobalt tablets was prescribed for 2 weeks. Before and after treatment, the scores of Northwick Park questionnaire (NPQ) and the simplified McGill pain questionnaire (SF-MPQ) were observed, and the safety was assessed in patients of the two groups. RESULTS: After treatment completion, the scores of NPQ and SF-MPQ were all reduced when compared with those before treatment in each group (P<0.001), and the scores of NPQ and SF-MPQ in the acupuncture group were lower than those of the non-acupuncture group (P<0.001). The incidence of adverse reactions was 6.0% (13/218) in the acupuncture group and was 10.1% (22/218) in the non-acupuncture group, without statistical significance in comparison (P>0.05). CONCLUSION: Acupuncture is effective and safe in the relief of neck pain and the improvement of comprehensive quality of life in the patients with cervical spondylosis.

Hsa_circRNA_103124 upregulation in Crohn's disease promoted macrophage M1 polarization to maintain an inflammatory microenvironment via activation of the AKT2 and TLR4/NF-κB pathways.

An accumulating body of research indicates that circular RNAs participate in the pathogenesis of Crohn's disease (CD). Hsa_circRNA_103124, which was upregulated in the peripheral blood mononuclear cells of patients with CD, was reported to inhibit autophagy in our previous studies. However, how hsa_circRNA_103124 participates in CD progression remains unclear. In this study, TLR4 was found to be upregulated in THP1 cells overexpressing hsa_circRNA_103124. Bioinformatic analysis indicated that overexpressed hsa_circRNA_103124 was associated with the PI3K/AKT signaling pathway and TLR4-associated innate immunity in inflammatory bowel disease. Therefore, we inferred a possible role for hsa_circRNA_103124 in macrophage polarization. Hsa_circRNA_103124, AKT2 and TLR4 were significantly upregulated in the PBMCs of patients with CD. Further analysis revealed a positive correlation between hsa_circRNA_103124 and AKT2 (r = 0.8029, p < 0.0001), TLR4 (r = 0.2529, p = 0.0089) and the Crohn's disease activity index (r = 0.4535, p < 0.0001) in patients with CD. Notably, hsa_circRNA_103124 promoted macrophage M1 polarization with increased expression of CD80 and CD86, while it inhibited macrophage M2 polarization with decreased expression of CD206 and CD163. Hsa_circRNA_103124 promoted an inflammatory microenvironment by activating the AKT2 and TLR4/NF-κB signaling pathways in M1 polarized THP1 cells. Nevertheless, hsa-miR-650 reversed the role of hsa_circRNA_103124 in M1 polarization. Hsa_circRNA_103124 promoted the formation of neutrophil extracellular traps and reduced the expression of ZO-1. In summary, the results of this study indicated that hsa_circRNA_103124 promoted macrophage M1 polarization to maintain an inflammatory microenvironment via activation of the TLR4/NF-κB pathway in a hsa-miR-650/AKT2 dependent manner. Hsa_circRNA_103124 could serve as a potential biomarker and a novel therapeutic target in CD progression.

Effects of biochar and zero valent iron on the bioavailability and potential toxicity of heavy metals in contaminated soil at the field scale.

Heavy metals (HMs) such as copper, nickel and chromium are toxic, so soil contaminated with these metals is of great concern. In situ HM immobilization by adding amendments can decrease the risk of contaminants being released. A five-month field-scale study was performed to assess how different doses of biochar and zero valent iron (ZVI) affect HM bioavailability, mobility, and toxicity in contaminated soil. The bioavailabilities of HMs were determined and ecotoxicological assays were performed. Adding 5 % biochar, 10 % ZVI, 2 % biochar + 1 % ZVI, and 5 % biochar + 10 % ZVI to soil decreased Cu, Ni and Cr bioavailability. Metals were most effectively immobilized by adding 5 % biochar + 10 % ZVI, and the extractable Cu, Ni, and Cr contents were 60.9 %, 66.1 % and 38.9 % lower, respectively, for soil with 5 % biochar + 10 % ZVI added than unamended soil. The extractable Cu, Ni, and Cr contents were 64.2 %, 59.7 % and 16.7 % lower, respectively, for soil with 2 % biochar + 1 % ZVI added than unamended soil. Experiments using wheat, pak choi and beet seedlings were performed to assess the remediated soil toxicity. Growth was markedly inhibited in seedlings grown in extracts of soil with 5 % biochar, 10 % ZVI, or 5 % biochar + 10 % ZVI added. More growth occurred in wheat and beet seedlings after 2 % biochar + 1 % ZVI treatment than the control, possibly because 2 % biochar + 1 % ZVI simultaneously decreased the extractable HM content and increased the soluble nutrient (carbon and Fe) content of the soil. A comprehensive risk assessment indicated that adding 2 % biochar + 1 % ZVI gave optimal remediation at the field scale. Using ecotoxicological methods and determining the bioavailabilities of HMs can allow remediation methods to be identified to efficiently and cost-effectively decrease the risks posed by multiple metals in soil at contaminated sites.

Effect of water and nitrogen coupling regulation on the growth, physiology, yield, and quality attributes and comprehensive evaluation of wolfberry (Lycium barbarum L.).

The characteristics of the growing environment (arid and semi-arid regions with abundant light), wastage of water, types of fertilizers used, quality of the plants, and the decline in yield due to the need for large quantities of water and fertilizers are the most significant obstacles to wolfberry cultivation. To cope with the scarcity of water caused by the increase in the area of wolfberry cultivation and to improve the efficiency of the utilization of water and fertilizers, a two-year field experiment was conducted in a typical area of the central dry zone of Ningxia in 2021 and 2022. The effects of different water and nitrogen coupling on the physiology, growth, quality, and yield of wolfberry were investigated, and a water and nitrogen management model with better indicators was constructed based on the TOPSIS model and a comprehensive scoring method. In the experiment, three irrigation quotas of 2,160, 2,565, and 2,970 m3 ha-1 (I1, I2, and I3) and three N applications of 165, 225, and 285 kg ha-1 (N1, N2, and N3) were established; the local conventional management served as the control (CK). The results showed that the growth index of wolfberry was most significantly affected by irrigation, followed by the water and nitrogen interaction effect, and the nitrogen application had the least effect. The growth and development of wolfberry plants mainly takes place during the fruit ripening and flowering periods, and growth almost stops after entering the fruit ripening period. The chlorophyll (SPAD) values were affected by irrigation and nitrogen application to a significant level, except for during the spring tip period, but the effect of water and nitrogen interaction was not significant. The SPAD values of N2 treatment were better under different irrigation. The daily photosynthetic activity of wolfberry leaves peaked between 10:00 am and noon. The daily photosynthetic dynamics of wolfberry were affected by irrigation and nitrogen application to a significant level during the fruit ripening period, and the transpiration rate and leaf water use efficiency were affected by water and nitrogen interaction to a significant level during 8:00 am and noon, while the effect was not significant during the spring tip period. The yield, dry-to-fresh ratio, and 100 grain weight of wolfberry were significantly affected by the irrigation, nitrogen application, and their interaction effects. Specifically, the two-year yield with I2N2 treatment increased by 7.48% and 3.73%, respectively, compared to CK. The quality indices were significantly affected by irrigation and nitrogen application, except for the total sugars; other indexes were also significantly affected by water and nitrogen interaction effects. The evaluation of the TOPSIS model showed that the I3N1 treatment yielded the best quality of wolfberry, and the results of the integrated scoring method based on the growth, physiology, yield, and quality indicators and water-saving objectives showed that the I2N2 (2,565 m3 ha-1, 225 kg ha-1) treatment was the optimal water and nitrogen management mode for drip-irrigated wolfberry. Our findings provide a scientific basis for the optimal irrigation and management of fertilization of wolfberry in arid regions.

Prostate organoids: emerging experimental tools for translational research.

Organoid technology has provided new translational research opportunities in oncology, in part by enabling the development of patient-representative living biobanks. Prostate cancer research historically has been constrained to a small number of in vitro models, limiting the ability to translate experimental conclusions for contemporary, heterogeneous patient populations. The facility of organoid culture methods to maintain luminal prostate epithelia, the common lineage of prostate cancers, has greatly expanded the phenotypic and genotypic diversity of available tractable models, including luminal stem/progenitor cells and progressive patient-derived cancers. Biobanks of patient prostate cancer organoids enable increased accuracy in predicting therapeutic efficacy and informative clinical trial designs. Here, we discuss how prostate organoid technology is currently being used, the promising areas of future therapeutic applications, and the current obstacles to be overcome.

MiR-18a-5p aggravates homocysteine-induced myocardial injury via autophagy. / MiR-18a-5pé€šè¿‡ä»‹å¯¼è‡ªå™¬åŠ é‡åŒåž‹åŠèƒ±æ°¨é ¸è¯±å¯¼çš„å¿ƒè‚ŒæŸä¼¤.

OBJECTIVES: Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury. METHODS: H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2. RESULTS: Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p. CONCLUSIONS: MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.

A mutation in CsABCB19 encoding an ATP-binding cassette auxin transporter leads to erect and compact leaf architecture in cucumber (Cucumis sativus L.).

Leaf architecture, including leaf position and leaf morphology, is a critical component of plant architecture that directly determines plant appearance, photosynthetic utilization, and ultimate productivity. The mechanisms regulating leaf petiole angle and leaf flatness in cucumber remain unclear. In this study, we identified an erect and compact leaf architecture mutant (ecla) from an EMS (ethyl methanesulfonate) -mutagenized cucumber population, which exhibited erect petioles and crinkled leaves. Histological examination revealed significant phenotypic variation in ecla was associated with asymmetric cell expansion. MutMap sequencing combined with genetic mapping revealed that CsaV3_5G037960 is the causative gene for the ecla mutant phenotype. Through protein sequence alignment and Arabidopsis genetic complementation, we identified this gene as a functional direct homolog encoding the ATP-binding cassette transporter AtABCB19, hence named CsABCB19. A nonsynonymous mutation in the eleventh exon of CsABCB19 leads to premature termination of translation. The expression level of CsABCB19 in the ecla mutant was significantly reduced in all tissues compared to the wild type (WT). Transcriptome analysis revealed that auxin and polarity-related genes were significantly differentially expressed in mutant petioles and leaves, compared with those in WT. Auxin assay and exogenous treatment further demonstrated that CsABCB19 regulates leaf architecture by mediating auxin accumulation and transport. Our research is the first report describing the role of the ABCB19 transporter protein in auxin transport controlling cucumber leaf development. Furthermore, this study provides recent insights into the genetic mechanisms conferring morphological diversity and regulation of petiole angle and leaf flattening. DATA AVAILABILITY: The RNA-seq data in this study have been deposited in the NCBI SRA under BioProject accession number PRJNA874548.

Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis.

Pulmonary fibrosis (PF) is a form of progressive lung disease characterized by chronic inflammation and excessive extracellular matrix (ECM) deposition. However, the protein changes in fibrotic ECM during PF and their contribution to fibrosis progression are unclear. Here we show that changes in expression of ECM components and ECM remodeling had occurred in silica-instilled mice. The macrophage-derived glycoprotein nonmetastatic melanoma protein B (GPNMB) captured by fibrotic ECM may activate resident normal fibroblasts around the fibrotic foci. Functional experiments demonstrated the activation of fibroblasts in fibrotic ECM, which was alleviated by GPNMB-neutralizing antibodies or macrophage deletion in the ECM of silica-instilled mice. Moreover, the Serpinb2 expression level was increased in fibroblasts in fibrotic ECM, and the expression of CD44 was increased in silica-instilled mice. In conclusion, macrophage-derived GPNMB is trapped by fibrotic ECM during transport and may activate fibroblasts via the CD44/Serpinb2 pathway, thus leading to the further development of fibrosis.

Evaluation of toxicological effects of bisphenol S with an in vitro human bone marrow mesenchymal stem cell: Implications for bone health.

As the use of bisphenol A (BPA) has been restricted in consumer products, bisphenol S (BPS) is one major alternative to BPA for various materials, leading to growing concerns about its health risks in human beings. However, little is known about the toxic effects of BPS on bone health. We employed human bone marrow mesenchymal stem cells (hBMSCs) for the in vitro assessment of BPS on cell proliferation, differentiation, and self-renewal. Our study revealed that BPS at concentrations of 10-10-10-7 M increased cell viability but induced the morphological changes of hBMSCs. Moreover, BPS decreased ROS generation and increased Nrf2 expression. Furthermore, BPS not only activated ERα/ß expression but also increased ß-catenin expression and induced the replicative senescence of hBMSCs. Furthermore, we found that the upregulation of ß-catenin induced by BPS was mediated, in part, by ER signaling. Overall, our results suggested BPS exposure caused the homeostatic imbalance of hBMSCs.