Green Synthesis and Biosafety Assessment of MXene.

The rise of MXene-based materials with fascinating physical and chemical properties has attracted wide attention in the field of biomedicine, because it can be exploited to regulate a variety of biological processes. The biomedical applications of MXene are still in its infancy, nevertheless, the comprehensive evaluation of MXene's biosafety is desperately needed. In this review, the composition and the synthetic methods of MXene materials are first introduced from the view of biosafety. The evaluation of the interaction between MXene and cells, as well as the safety of different forms of MXene applied in vivo are then discussed. This review provides a basic understanding of MXene biosafety and may bring new inspirations to the future applications of MXene-based materials in biomedicine.

Overexpression of HbGRF4 or HbGRF4-HbGIF1 Chimera Improves the Efficiency of Somatic Embryogenesis in Hevea brasiliensis.

Transgenic technology is a crucial tool for gene functional analysis and targeted genetic modification in the para rubber tree (Hevea brasiliensis). However, low efficiency of plant regeneration via somatic embryogenesis remains a bottleneck of successful genetic transformation in H. brasiliensis. Enhancing expression of GROWTH-REGULATING FACTOR 4 (GRF4)-GRF-INTERACTING FACTOR 1 (GIF1) has been reported to significantly improve shoot and embryo regeneration in multiple crops. Here, we identified endogenous HbGRF4 and HbGIF1 from the rubber clone Reyan7-33-97, the expressions of which dramatically increased along with somatic embryo (SE) production. Intriguingly, overexpression of HbGRF4 or HbGRF4-HbGIF1 markedly enhanced the efficiency of embryogenesis in two H. brasiliensis callus lines with contrasting rates of SE production. Transcriptional profiling revealed that the genes involved in jasmonic acid response were up-regulated, whereas those in ethylene biosynthesis and response as well as the S-adenosylmethionine-dependent methyltransferase activity were down-regulated in HbGRF4- and HbGRF4-HbGIF1-overexpressing H. brasiliensis embryos. These findings open up a new avenue for improving SE production in rubber tree, and help to unravel the underlying mechanisms of HbGRF4-enhanced somatic embryogenesis.

PSMC4 promotes prostate carcinoma progression by regulating the CBX3-EGFR-PI3K-AKT-mTOR pathway.

Proteasome 26S subunit ATPase 4 (PSMC4) could regulate cancer progression. However, the function of PSMC4 in prostate carcinoma (PCa) progression requires further clarification. In the study, PSMC4 and chromobox 3 (CBX3) levels were verified by TCGA data and tissue microarrays. Cell counting kit-8, cell apoptosis, cell cycle, wound healing, transwell and xenograft tumour model assays were performed to verify biological functions of PSMC4 in PCa. RNA-seq, PCR, western blotting and co-IP assays were performed to verify the mechanism of PSMC4. Results showed that PSMC4 level was significantly increased in PCa tissues, and patients with PCa with a high PSMC4 level exhibited shorter overall survival. PSMC4 knockdown markedly inhibited cell proliferation, cell cycle and migration in vitro and in vivo, and significantly promoted cell apoptosis. Then further study revealed that CBX3 was a downstream target of PSMC4. PSMC4 knockdown markedly reduced CBX3 level, and inhibited PI3K-AKT-mTOR signalling. CBX3 overexpression markedly promoted epidermal growth factor receptor (EGFR) level. Finally, PSMC4 overexpression showed reverse effect in DU145 cells, and the effects of PSMC4 overexpression on cell proliferation, migration and clonal formation were rescued by the CBX3 knockdown, and regulated EGFR-PI3K-AKT-mTOR signalling. In conclusion, PSMC4 could regulate the PCa progression by mediating the CBX3-EGFR-PI3K-AKT-mTOR pathway. These findings provided a new target for PCa treatment.

Investigation on the mechanisms of human sperm DNA damage based on the proteomics analysis by SWATH-MS.

BACKGROUND: Spermatozoa have the task of delivering an intact paternal genome to the oocyte and supporting successful embryo development. The detection of sperm DNA fragmentation (SDF) has been emerging as a complementary test to conventional semen analysis for male infertility evaluation, but the mechanism leading to SDF and its impact on assisted reproduction remain unclear. Therefore, the study identified and analyzed the differentially expressed proteins of sperm with high and low SDF. METHODS: Semen samples from men attended the infertility clinic during June 2020 and August 2020 were analyzed, and sperm DNA fragmentation index (DFI) was detected by the sperm chromatin structure assay. Semen samples with low DFI (< 30%, control group) and high DFI (≥ 30%, experimental group) were optimized by density gradient centrifugation (DGC), and the differentially expressed proteins of obtained sperm were identified by the Sequential Window Acquisition of All Theoretical Mass Spectra Mass Spectrometry (SWATH-MS) and performed GO and KEGG analysis. RESULTS: A total of 2186 proteins were identified and 1591 proteins were quantified, of which 252 proteins were identified as differentially expressed proteins, including 124 upregulated and 128 downregulated. These differentially expressed proteins were involved in metabolic pathways, replication/recombination/repair, acrosomal vesicles, kinase regulators, fertilization, tyrosine metabolism, etc. Western blotting results showed that the expression levels of RAD23B and DFFA proteins and the levels of posttranslational ubiquitination and acetylation modifications in the experimental group were significantly higher than those in the control group, which was consistent with the results of proteomics analysis. CONCLUSIONS: Proteomic markers of sperm with high DNA fragmentation can be identified by the SWATH-MS and bioinformatic analysis, and new protein markers and posttranslational modifications related to sperm DNA damage are expected to be intensively explored. Our findings may improve our understanding of the basic molecular mechanism of sperm DNA damage.

Forms of nitrogen inputs regulate the intensity of soil acidification.

Soil acidification induced by reactive nitrogen (N) inputs can alter the structure and function of terrestrial ecosystems. Because different N-transformation processes contribute to the production and consumption of H+ , the magnitude of acidification likely depends on the relative amounts of organic N (ON) and inorganic N (IN) inputs. However, few studies have explicitly measured the effects of N composition on soil acidification. In this study, we first conducted a meta-analysis to test the effects of ON or IN inputs on soil acidification across 53 studies in grasslands. We then compared soil acidification across five different ON:IN ratios and two input rates based on long-term field N addition experiments. The meta-analysis showed that ON had weaker effects on soil acidification than IN when the N addition rate was above 20 g N m-2 year-1 . The field experiment confirmed the findings from meta-analysis: N addition with proportions of ON ≥ 20% caused less soil acidification, especially at a high input rate (30 g N m-2 year-1 ). Structural equation model analysis showed that this result was largely due to a relatively low rate of H+ production from ON as NH3 volatilization and uptake of ON and NH4 + by the dominant grass species Leymus chinensis (which are both lower net contributors to H+ production) result in less NH4 + available for nitrification (which is a higher net contributor to H+ production). These results indicate that the evaluation of soil acidification induced by N inputs should consider N forms and manipulations of relative composition of N inputs may provide an effective approach to alleviate the N-induced soil acidification.

Investigation of the mechanisms leading to human sperm DNA damage based on transcriptome analysis by RNA-seq techniques.

RESEARCH QUESTION: What are the molecular mechanisms leading to human sperm DNA damage? DESIGN: Semen samples were collected and the sperm DNA fragmentation index (DFI) was assessed. Differentially expressed RNA in spermatozoa with a high (DFI ≥30%, experimental group) or normal (DFI <30%, control group) DFI were identified by RNA-sequencing (RNA-seq) technology, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed. Three differentially expressed RNA related to sperm DNA damage and repair, namely PMS1, TP53BP1 and TLK2, were validated using real-time quantitative (RT-qPCR). RESULTS: A total of 19,970 expressed RNA were detected in the two groups. Compared with the control group, the expression levels of 189 RNA in the experimental group were significantly increased and those of 163 genes decreased. Gene Ontology enrichment analysis showed that these RNA were mainly concentrated in the ATPase-dependent transmembrane transport complex, extracellular exosome, somatic cell DNA recombination, protein binding, cytoplasm and regulation of localization. KEGG pathway analysis showed that these RNA were mainly related to the PI3K-Akt signalling pathway, endocytosis, p53 signalling pathway and cGMP-PKG signalling pathway. The RT-qPCR results showed that the expression levels of PMS1, TP53BP1 and TLK2 in the experimental group were significantly lower than in the control group (P = 0.01, 0.015 and 0.004, respectively), which was identical to the results of RNA sequencing. CONCLUSIONS: Differentially expressed RNA related to sperm DNA damage and repair may be identified by RNA-seq technology, which provides new insights into the understanding of sperm DNA damage and repair, and will help to discover new biomarkers related to sperm DNA damage.

[Clinical observation of dapoxetine combined with percutaneous neuromuscular electrical stimulation in the treatment of primary premature ejaculation].

OBJECTIVE: To investigate the clinical efficacy of dapoxetine combined with transcutaneous neuromuscular electrical stimulation (TNES) in the treatment of primary premature ejaculation. METHODS: A total of 60 patients who met the diagnostic criteria for primary premature ejaculation were selected as study subjects and randomly divided into a dapoxetine group (control group) and a dapoxetine combined with percutaneous neuromuscular electrical stimulation group (observation group).30 patients in each group were treated for 4 weeks. Intravaginal ejaculatory latency time (IELT), the score of Premature Ejaculation Diagnostic Tool (PEDT), sympathetic skin response located in the penis (PSSR), Patient Health Questionnaire (PHQ-9), and Generalized Anxiety Disorder Questionnaire (GAD-7) before and after treatment were recorded in the two groups. Before and after treatment, the difference in observed indexes in the two groups and the comparison of effective rates between the two groups were analyzed. RESULTS: The latency of IELT and PSSR was prolonged and the PEDT score was decreased in both the observation group and the control group, the difference was statistically significant (P<0.01). Compared with the control group, the observation group had statistically significant differences in extending IELT and PSSR latency and reducing PEDT score (P<0.05). The effective rates of the observation group and control group were 90% and 63.33%, respectively, and the difference was statistically significant (P<0.05). There was no significant difference in the improvement of depression and anxiety levels between the two groups (P> 0.05). CONCLUSION: Dapoxetine combined with TNES has a better clinical effect than dapoxetine alone in the treatment of primary premature ejaculation, and can be used as an effective option for clinical treatment of primary premature ejaculation.

Endowing Polyetheretherketone Implants with Osseointegration Properties: In Situ Construction of Patterned Nanorod Arrays.

Polyetheretherketone (PEEK) is widely used in orthopedic and craniomaxillofacial surgeries as it exhibits excellent biocompatibility, mechanical property, and chemical stability. However, its clinical application is limited by the biological inertness of PEEK. Numerous efforts have been made to improve the bioactivity of this polymer over the years. However, modification methods that can not only promote osteogenesis but also maintain excellent properties are still limited. Hence, a facile hot die formation technique is developed for establishing patterned nanorod arrays on the PEEK surface in situ. This method can maintain the excellent properties of PEEK and can be used in implantation as it can facilitate osteogenic activity in the absence of any organic/inorganic differentiation-inducing factors. PEEK with 200-nm patterned nanorod arrays on the surface exhibits excellent osteogenic properties. This result is obtained by assessing the osteogenic differentiation properties of rat adipose-derived stem cells at the gene and protein levels in vitro. In vivo experimental results reveal that the surface-modified cylindrical PEEK 200 implants present with excellent osseointegration properties. Moreover, they can tightly bind with the surrounding bone tissue. A practical method for manufacturing single-component PEEK implants with excellent osseointegration properties is reported, and the materials can be possibly used as orthopedic implants.

Polymeric Systems for Bioprinting.

Bioprinting is rapidly being adopted as a major method for fabricating tissue engineering constructs. Through the precise deposition of cell- and bioactive molecule-laden materials, bioprinting offers researchers a means to create biological constructs with enhanced spatial complexity that more closely mimics native tissue. The vast majority of materials used in bioprinting have been polymers due to their suitability toward resembling the cellular environment and the variety of methods available to process polymeric systems in ambient or relatively mild chemical and environmental conditions. In this review, we will discuss in detail the wide variety of natural and synthetic polymers that have been employed as inks in bioprinting. We will review recent bioprinting innovations, such as increasing architectural complexity and cell viability in heterogeneous tissue constructs, which allow for the investigation of biological questions that could not be addressed before. We will also survey nascent fields of study that promise to further advance the development of novel biofabrication technologies in the field, such as 4D bioprinting and the inclusion of nanomaterials. To conclude, we will examine some of the necessary steps that must take place to bring this technology to commercial markets and facilitate its use in clinical therapies.

Development and validation of a prediction model of catheter-related thrombosis in patients with cancer undergoing chemotherapy based on ultrasonography results and clinical information.

Central venous catheters can be used conveniently to deliver medications and improve comfort in patients with cancer. However, they can cause major complications. The current study aimed to develop and validate an individualized nomogram for early prediction of the risk of catheter-related thrombosis (CRT) in patients with cancer receiving chemotherapy. In total, 647 patients were included in the analysis. They were randomly assigned to the training (n = 431) and validation (n = 216) cohorts. A nomogram for predicting the risk of CRT in the training cohort was developed based on logistic regression analysis results. The accuracy and discriminatory ability of the model were determined using area under the receiver operating characteristic curve (AUROC) values and calibration plots. Multivariate logistic regression analysis showed that body mass index, risk of cancer-related thrombosis, D-dimer level, and blood flow velocity were independent risk factors of CRT. The calibration plot showed an acceptable agreement between the predicted and actual probabilities of CRT. The AUROC values of the nomogram were 0.757 (95% confidence interval: 0.717-0.809) and 0.761 (95% confidence interval: 0.701-0.821) for the training and validation cohorts, respectively. Our model presents a novel, user-friendly tool for predicting the risk of CRT in patients with cancer receiving chemotherapy. Moreover, it can contribute to clinical decision-making.

TiSe2-mediated sonodynamic and checkpoint blockade combined immunotherapy in hypoxic pancreatic cancer.

BACKGROUND: Pancreatic cancer remains among the most prevalent and aggressive forms of cancer. While immunotherapeutic treatment strategies have shown some promise in affected patients, the benefits of these interventions have been limited by insufficient tumor infiltration by activated T cells. RESULTS: Here, Titanium diselenide (TiSe2) nanosheets were synthesized with good stability. When exposed to ultrasound (US), the TiSe2 nanosheets served as a reliable nano-sensitizer capable of inducing large amounts of reactive oxygen species (ROS) mediating sonodynamic therapy (SDT) under hypoxic and normoxic conditions. The tumor-released TAAs induced by TiSe2 nanosheet-mediated SDT promoted immunogenic cell death (ICD) conducive to the maturation of dendritic cells (DCs), and cytokine secretion and the subsequent activation and infiltration of T cells into the tumor. Combining TiSe2-mediated SDT with anti-PD-1 immune checkpoint blockade treatment led to the efficient suppression of the growth of both primary tumor and distant tumor, while simultaneously preventing lung metastasis. These improved immunotherapeutic and anti-metastatic outcomes were associated with activated systematic antitumor immune responses, including the higher levels of DC maturation and cytokine secretion, the increased levels of CD8+ T cells and the decreased levels of Treg cells infiltrated in tumors. CONCLUSION: TiSe2 can be used as a sonosensitizer with good efficacy and high safety to mediate efficient SDT. The combination treatment strategy comprised of TiSe2-mediated SDT and PD-1 blockade activate anti-tumor immune responses effectively thorough inducing ICD, resulting in the inhibition the growth and metastasis of tumor. The combination therapy holds promise as a novel immunotherapy-based intervention strategy for pancreatic cancer patients.

The value of contrast-enhanced ultrasonography in the diagnosis of primary testicular non-neoplastic and neoplastic lesions in adults.

BACKGROUND: Different pathological types of testicular tumors are treated differently. Malignant germ cell tumors require radical orchiectomy, while benign tumors may only need mass enucleation. Contrast-enhanced ultrasonography (CEUS) is more sensitive than conventional ultrasonography in displaying tumor microvessels, which helps distinguish between benign and malignant tumors. METHODS: This was a retrospective analysis of 35 patients with pathological-confirmed primary testicular non-neoplastic and neoplastic lesions in our hospital from February 2017 to February 2022. Conventional ultrasonography and CEUS imaging findings of included lesions were retrospectively analyzed and their diagnostic values were compared with the pathological results. RESULTS: There were 13 cases of benign testicular lesions (including 1 case of spontaneous hematoma, 2 cases of segmental infarctions, 5 cases of epidermoid cysts, 2 cases of Sertoli cell tumors, and 3 cases of Leydig cell tumors) and 23 cases of malignant testicular lesions (including 10 cases of seminomas, 1 case of embryonal carcinoma, 2 cases of mixed germ cell tumors, 2 cases of spermatocytic tumors, and 8 cases of lymphomas). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates of conventional ultrasound in diagnosing benign testicular tumors by "onion skin-like" echo (epidermoid cysts) and peripheral annular blood flow were 30.8%, 100.0%, 100.0%, 71.9% and 75.0%, respectively. All testicular non-neoplastic lesions and epidermoid cysts showed no enhancement by CEUS. All Sertoli-Leydig cell tumors (SLCTs)' CEUS imaging showed uniform high enhancement (no necrosis area), fast forward, and slow backward. 80.0% (12/15) malignant germ cell tumors showed heterogeneous enhancement and fast forward and fast backward in CEUS. All lymphomas showed fast forward and fast backward, and 87.5% (7/8) of them showed uniform high levels of enhancement in CEUS. According to CEUS without enhancement (non-neoplastic lesions and epidermoid cysts) and uniform high enhancement with fast forward and slow backward (SLCT), the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates for diagnosing benign testicular tumors were all 100.0%. Compared with conventional ultrasound, the difference was statistically significant (p = 0.004). CONCLUSIONS: CEUS could accurately distinguish between benign and malignant testicular tumors, as well as differentiate specific pathological types (testicular focal infarction, epidermoid cysts, spermatocytic tumors, SLTC and lymphoma). Accurate preoperative diagnosis is critical for guiding the selection of appropriate treatment plans for different pathological types of testicular tumors.

[Transcutaneous neuromuscular electrical stimulation for the treatment of erectile dysfunction: A clinical observation].

OBJECTIVE: To observe the clinical efficacy of transcutaneous neuromuscular electrical stimulation (TNES) in the treatment of ED. METHODS: According to the inclusion and exclusion criteria, we included and studied 25 cases of ED treated by TNES in Northern Jiangsu People's Hospital from June 2021 to February 2022 using the self-matched pre- and post-control method. Before and after treatment, we conducted RigiScan penile hardness test under audiovisual sexual stimulation (AVSS) for all the patients and obtained their scores on the Erectile Hardness Scale (EHS), IIEF-5, Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire 9 (PHQ-9) and Generalized Anxiety Disorder Questionnaire 7 (GAD-7). RESULTS: No adverse reactions such as pain, allergy, skin burn, and subcutaneous congestion were observed in any of the patients. There were statistically significant differences after treatment in erection time, average and maximum hardness of the penile tip, mean hardness of the penile root, and circumference of the penile tip (P < 0.05), but not in the circumference and maximum hardness of the penile root during erection compared with the baseline (P > 0.05). Significant improvement was observed after treatment in the IIEF-5 score (P < 0.05), with a total effectiveness rate of 68%, as well as in the PEDT score (P < 0.05) GAD-7 anxiety score (P < 0.05), but not in the PHQ-9 depression score (P > 0.05). CONCLUSION: TNES, as a safe and non-invasive therapy, can improve penile hardness under AVSS and the erectile function and anxiety symptoms of ED patients, and can be used as a new option for the treatment of ED.

Metabolic syndrome, high-sensitivity C-reactive protein levels and the risk of new-onset atrial fibrillation: Results from the Kailuan Study.

BACKGROUND AND AIMS: Some studies have reported that metabolic syndrome (MS) and a high inflammatory state are risk factors for atrial fibrillation (AF). However, the combined effect of MS and a high inflammatory state on AF is still unknown. We aimed to investigate the association of MS and high-sensitivity C-reactive protein (hs-CRP) levels with the risk of AF in a large community-based population. METHODS AND RESULTS: A total of 81,092 subjects from the Kailuan Study with electrocardiogram examination and hs-CRP data at baseline (1st examination, 2006-2007) were included in this study. The enrolled population was divided into 4 groups according to the presence or absence of metabolic syndrome and high hs-CRP (>3 mg/L). The follow-up examinations were performed every two years (2nd examination, 2008-2009; 3rd examination, 2010-2011; 4th examination, 2012-2013; 5th examination, 2014-2015). All participants were followed until the occurrence of AF or the date of the last examination. After a mean time of 7.2 ± 2.0 years, a total of 271 individuals developed incident AF. MS or high hs-CRP alone was not associated with incident AF after multivariable adjustment. However, multiple Cox regression analysis showed that subjects with MS and hs-CRP > 3 mg/L had a greater risk for AF than those without MS and with hs-CRP ≤ 3 mg/L (hazard ratio, 1.61; 95% confidence interval 1.08-2.41; P = 0.019). CONCLUSION: MS combined with a high hs-CRP level is associated with an increased risk for AF in the Chinese population. However, the mechanism is unknown and awaits further study. TRIAL REGISTRATION SITE: http://www.chictr.org.cn/index.aspx. REGISTRATION NUMBER: ChiCTR-TNRC-11001489.

Deep Penetration of Targeted Nanobubbles Enhanced Cavitation Effect on Thrombolytic Capacity.

Sonothrombolysis with microbubbles can enhance the dissolution of thrombus through the cavitation effect of microbubbles under ultrasound irradiation. However, the detailed mechanism of thrombolysis with microscaled or nanoscaled bubbles is still not so clear. This study compared the thrombolytic capacity of cRGD-targeted or nontargeted bubbles with different particle sizes combined with urokinase (UK). The size of the microscaled bubbles (Mbs or Mbs-cRGD) was mostly approximately 3 µm, while the nanoscaled bubbles (Nbs or Nbs-cRGD) were mainly around 220 nm. In vitro testing was performed on an extracorporeal circulation device that mimics human vascular thromboembolism. The rabbit clots in Mbs with UK groups showed peripheral worm-like dissolution, while the clots in Nbs with UK groups showed internal fissure-like collapse. In addition, the thrombolysis rate of Nbs-cRGD with the UK group was the highest. Furthermore, the scanning electron microscopic images showed that the fibrin network was the most severely damaged by the Nbs-cRGD, and most of the fibrin strands were dissolved. Especially, the Nbs-cRGD can penetrate much deeper than Mbs-cRGD into the thrombus and loosen the fibrin network. Taken together, benefiting from the specific identification and deep penetration to thrombus, our developed novel targeted Nbs may have broad application prospects in the clinic.

Coherent Electron Transfer at the Ag/Graphite Heterojunction Interface.

Charge transfer in transduction of light to electrical or chemical energy at heterojunctions of metals with semiconductors or semimetals is believed to occur by photogenerated hot electrons in metal undergoing incoherent internal photoemission through the heterojunction interface. Charge transfer, however, can also occur coherently by dipole coupling of electronic bands at the heterojunction interface. Microscopic physical insights into how transfer occurs can be elucidated by following the coherent polarization of the donor and acceptor states on the time scale of electronic dephasing. By time-resolved multiphoton photoemission spectroscopy (MPP), we investigate the coherent electron transfer from an interface state that forms upon chemisorption of Ag nanoclusters onto graphite to a σ symmetry interlayer band of graphite. Multidimensional MPP spectroscopy reveals a resonant two-photon transition, which dephases within 10 fs completing the coherent transfer.

Zinc finger of Arabidopsis thaliana 6 is involved in melatonin-mediated auxin signaling through interacting INDETERMINATE DOMAIN15 and INDOLE-3-ACETIC ACID 17.

Although accumulating evidence demonstrates the cross talk between melatonin and auxin as derivatives of tryptophan, the underlying signaling events remain unclear. In this study, we found that melatonin and auxin mediated the transcriptional levels of zinc finger of Arabidopsis thaliana (ZAT6) in a mutually antagonistic manner. ZAT6 negatively modulated the endogenous auxin level, and ZAT6 knockdown plants were less sensitive to melatonin-regulated auxin biosynthesis, indicating its involvement in melatonin-mediated auxin accumulation. Additionally, the identification of INDETERMINATE DOMAIN15 (IDD15) and INDOLE-3-ACETIC ACID 17 (IAA17) in Arabidopsis that interacted with ZAT6 in vivo provided new insight of ZAT6-mediated auxin signaling. Further investigation showed that ZAT6 repressed the transcription activation of IDD15 on the YUC2 promoter, while ZAT6 inhibited the interaction of TRANSPORT INHIBITOR RESPONSE 1 (TIR1) and IAA17 through competitively binding to IAA17. Thus, both auxin synthesis and the auxin response were negatively modulated by ZAT6. Taken together, ZAT6 is involved in melatonin-mediated auxin signaling through forming an interacting complex of auxin signaling pathway in Arabidopsis.

Effects of high-intensity focused ultrasound on cisplatin-resistant human lung adenocarcinoma in vitro and in vivo.

It is widely accepted that high-intensity focused ultrasound (HIFU) is a minimally invasive treatment option for different tumors, but its roles and the corresponding mechanism in cisplatin (DDP) chemoresistance in lung adenocarcinoma (LA) remain unclear. In this study, we investigated the response of DDP-resistant LA cells to HIFU and its underlying molecular mechanisms using molecular biology techniques. It was found that HIFU exposure inhibited the proliferation of DDP-resistant A549 (A549/DDP) cells through arresting cell cycle at the G1/G0 phase via the Cyclin-dependent pathway and promoting apoptosis in a Bcl-2-dependent manner. Furthermore, the results also showed that HIFU exposure could down-regulate the expressions of MDR1, MRP1, and LRP mRNAs, as well as P-gp, MRP1, and LRP proteins related to drug resistance in A549/DDP cells. In vivo experiments also demonstrated that HIFU could reduce the size and mass of subcutaneously transplanted tumors produced by A549/DDP cells through mediating Cyclin-dependent and Bcl-2-dependent pathways. These results suggested that HIFU treatment could inhibit the proliferation of DDP-resistant lung cancer cells and might be a novel therapeutic method for patients with DDP resistance.

Chimeric Protein Template-Induced Shape Control of Bone Mineral Nanoparticles and Its Impact on Mesenchymal Stem Cell Fate.

Protein-mediated molecular self-assembly has become a powerful strategy to fabricate biomimetic biomaterials with controlled shapes. Here we designed a novel chimeric molecular template made of two proteins, silk fibroin (SF) and albumin (ALB), which serve as a promoter and an inhibitor for hydroxyapatite (HA) formation, respectively, to synthesize HA nanoparticles with controlled shapes. HA nanospheres were produced by the chimeric ALB-SF template, whereas HA nanorods were generated by the SF template alone. The success in controlling the shape of HA nanoparticles allowed us to further study the effect of the shape of HA nanoparticles on the fate of rat mesenchymal stem cells (MSCs). We found that the nanoparticle shape had a crucial impact on the cellular uptake and HA nanospheres were internalized in MSCs at a faster rate. Both HA nanospheres and nanorods showed no significant influence on cell proliferation and migration. However, HA nanospheres significantly promoted the osteoblastic differentiation of MSCs in comparison to HA nanorods. Our work suggests that a chimeric combination of promoter and inhibitor proteins is a promising approach to tuning the shape of nanoparticles. It also sheds new light into the role of the shape of the HA nanoparticles in directing stem cell fate.

Exploratory analysis on the association of dietary live microbe and non-dietary prebiotic/probiotic intake with serum cotinine levels in the general adult population.

Background: Previous research has indicated the potential involvement of the microbiota in smoking-related processes. The present study seeks to examine the relationship between dietary live microbes, as well as probiotic or prebiotic consumption, and serum cotinine levels. Methods: This study used data from the National Health and Nutrition Examination Survey 1999-2018. Dietary intake information and probiotic/prebiotic intake data was collected through self-reported questionnaires. Participants were stratified into low, medium, and high intake groups according to their consumption of foods with varying microbial content. Multiple linear models were applied to explore the relationships of dietary live microbes, probiotic or prebiotic use with the serum cotinine level. Results: A total of 42,000 eligible participants were included in the final analysis. The weighted median serum cotinine level was 0.05 (0.01, 10.90) ng/ml. Participants with low, medium, and high dietary microbe intake represented 35.4, 43.6, and 21.0% of the cohort, respectively. Furthermore, participants were stratified into three groups based on their overall consumption of foods with variable microbe contents. The association between dietary live microbe intake and serum cotinine levels remained robust across all models, with medium intake as the reference (Model 2: ß = -0.14, 95% CI: -0.20, -0.07; High: ß = -0.31, 95% CI: -0.39, -0.22). Moreover, both prebiotic and probiotic use exhibited an inverse relationship with serum cotinine levels (Prebiotic: ß = -0.19, 95% CI: -0.37, -0.01; Probiotic: ß = -0.47, 95% CI: -0.64, -0.30). Subgroup analyses revealed no discernible interactions between dietary live microbe, prebiotic, probiotic use, and serum cotinine levels. Conclusion: Our findings suggest a negative correlation between dietary live microbe intake, as well as non-dietary prebiotic/probiotic consumption, and serum cotinine levels.