DeePMD-kit v2: A software package for deep potential models.

DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features, such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, DP-range correction, DP long range, graphics processing unit support for customized operators, model compression, non-von Neumann molecular dynamics, and improved usability, including documentation, compiled binary packages, graphical user interfaces, and application programming interfaces. This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, this article presents a comprehensive procedure for conducting molecular dynamics as a representative application, benchmarks the accuracy and efficiency of different models, and discusses ongoing developments.

[Multiple precision behavioral therapy for mild to moderate stress urinary incontinence with sexual dysfunction in women].

OBJECTIVE: To explore the clinical effect of multiple precision behavioral therapy (MPBT) on mild to moderate stress urinary incontinence (SUI) with female sexual dysfunction (FSD) in women. METHODS: We randomly divided 90 female patients with mild to moderate SUI with FSD into three groups of an equal number: control group A, control group B and an MPBT group, treated by electrical stimulation, Kegel training and MPBT, respectively, all for 8 weeks. Using International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Incontinence Impact Questionnaire (IIQ-7), Female Sexual Function Indexes (FSFI) and Glazer protocol, we evaluated the clinical effects, recorded the cost of treatment, and compared them among the three groups of patients. RESULTS: Totally, 87 of the patients completed the treatment, 27 in control group A, 30 in control group B and 30 in the MPBT group. There was no significant difference in the baseline data among the three groups (P > 0.05). ICIQ-SF and IIQ-7 scores, FSFI and Glazer values were remarkably improved in the MPBT group after treatment (P < 0.05). The therapeutic effect was significantly better and the treatment cost markedly lower in the MPBT than in the control groups (P < 0.05). CONCLUSION: Multiple precision behavioral therapy can effectively improve the clinical symptoms of mild to moderate stress urinary incontinence and sexual dysfunction in women, with low cost and high safety.

Interleukin-1ß augments the angiogenesis of endothelial progenitor cells in an NF-κB/CXCR7-dependent manner.

Endothelial progenitor cells (EPCs) are able to trigger angiogenesis, and pro-inflammatory cytokines have beneficial effects on angiogenesis under physiological and pathological conditions. C-X-C chemokine receptor type 7 (CXCR-7), receptor for stromal cell-derived factor-1, plays a critical role in enhancing EPC angiogenic function. Here, we examined whether CXCR7 mediates the pro-angiogenic effects of the inflammatory cytokine interleukin-1ß (IL-1ß) in EPCs. EPCs were isolated by density gradient centrifugation and angiogenic capability was evaluated in vitro by Matrigel capillary formation assay and fibrin gel bead assay. IL-1ß elevated CXCR7 expression at both the transcriptional and translational levels in a dose- and time-dependent manner, and blockade of the nuclear translocation of NF-κB dramatically attenuated the IL-1ß-mediated up-regulation of CXCR7 expression. IL-1ß stimulation significantly promoted EPCs tube formation and this effect was largely impaired by CXCR7-siRNA transfection. IL-1ß treatment stimulated extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and inhibition of Erk1/2 phosphorylation partially impaired IL-1ß-induced tube formation of EPCs but without significant effects on CXCR7 expression. Moreover, blocking NF-κB had no significant effects on IL-1ß-stimulated Erk1/2 phosphorylation. These findings indicate that CXCR7 plays an important role in the IL-1ß-enhanced angiogenic capability of EPCs and antagonizing CXCR7 is a potential strategy for inhibiting angiogenesis under inflammatory conditions.

Overexpressed miR-128a enhances chemoradiotherapy to laryngeal cancer cells and its correlation with BMI1.

AIM: To clarify the function of miR-128a on radiotherapy and chemotherapy resistance in laryngeal cancer and explore the possible mechanism. MATERIALS & METHODS: Hep-2 and AMC-HN-8 cell lines were cultured. MiR-128a was upregulated utilizing lentiviral transfection. Through radiotherapy and chemotherapy assays, the function of miR-128a on chemoradiotherapy was evaluated. The correlation of miR-128a with BMI1 was identified by performing real-time PCR. RESULTS: The hsa-miR128a cell line was established. The chemotherapy assay revealed that an overexpression of miR-128a decreases the inhibition to chemotherapy. The radiotherapy assay showed that miR-128a promotes the radiotherapy sensitivity. The expression of BMI1 decreased with overexpression of miR-128a. CONCLUSION: miR-128a confers chemoradiotherapy sensitivity of laryngeal cancer cells and targeting BMI1 gene is a possible mechanism of the effect.

Laser-induced locally controllable craze-like microstructures for polymer white structural coloration.

As a promising candidate for the inkless coloring method, white structural color has undergone widespread investigation because of its fascinating properties. Recently, various methods have been developed to prepare disordered micro/nanostructures to produce white structural color. However, complex and high-cost processing procedures severely restrict the efficient and large-scale preparation of disordered micro/nanostructures for achieving white structural color. Herein, we report an ingenious way to realize white structural color by laser-inducing craze-like microstructures in core-shell microfiber-based polymers. A microfiber with copper nanowires (CuNWs) as the core surrounded by a polyformaldehyde (POM) shell is prepared by a simple in situ fibrillation method. The craze-like microstructures with micro/nanofibrils and micropores are locally constructed in polymers by a facile, efficient, inexpensive, controllable, and environmentally friendly laser direct writing (LDW) technique. Ascribed to the broadband visible light reflection caused by disordered microstructures, the laser-induced craze-like microstructures in polymers based on CuNWs@POM core-shell microfibers exhibit a distinct white structural color. This work paves a way for achieving white structural color and provides a novel insight for utilizing the previously considered useless crazing phenomenon.

A simplified synthetic rhizosphere bacterial community steers plant oxylipin pathways for preventing foliar phytopathogens.

Rhizosphere-enriched microbes induced by foliar phytopathogen infection can be assembled into a functional community to enhance plant defense mechanisms. However, the functions of stably-colonizing rhizosphere microbiota are rarely investigated. In this study, Botrytis cinerea infection changed rhizosphere bacterial communities in tomato plants. The phytopathogen-infected plants recruited specific rhizosphere bacterial taxa, while several bacterial taxa stably colonized the rhizosphere, regardless of phytopathogen infection. Through the analysis of the rhizosphere bacterial community, we established a synthetic community harboring 8 phytopathogen-inducible and 30 stably-colonizing bacteria species. Furthermore, the 38-species community was simplified into a three-species community, consisting of one phytopathogen-inducible (Asticcacaulis sp.) and two stably-colonizing species (Arachidicoccus sp. And Phenylobacterium sp.). The simplified community provided a durable protection for the host plants by synergistic effects, with the phytopathogen-inducible species triggering plant defense responses and the stably-colonizing species promoting biofilm formation. The simplified community exhibited similar protective effects as the 38-species community. Moreover, the activation of oxylipin pathways in the phytopathogen-infected leaves was significantly intensified by the simplified community. However, the inhibited biosynthesis of antimicrobial divinyl ethers, including colneleic and colnelenic acid, fully abolished the community-induced plant disease resistance. In contrast, transgenic plants overexpressing SlLOX5 and SlDES1, with higher levels of divinyl ethers, displayed stronger resistance against B. cinerea compared to wild-type plants. Collectively, these findings provided insights into the utilization of the simplified community for preventing gray mold disease.

Development of plant systemic resistance by beneficial rhizobacteria: Recognition, initiation, elicitation and regulation.

A plant growing in nature is not an individual, but it holds an intricate community of plants and microbes with relatively stable partnerships. The microbial community has recently been demonstrated to be closely linked with plants since their earliest evolution, to help early land plants adapt to environmental threats. Mounting evidence has indicated that plants can release diverse kinds of signal molecules to attract beneficial bacteria for mediating the activities of their genetics and biochemistry. Several rhizobacterial strains can promote plant growth and enhance the ability of plants to withstand pathogenic attacks causing various diseases and loss in crop productivity. Beneficial rhizobacteria are generally called as plant growth-promoting rhizobacteria (PGPR) that induce systemic resistance (ISR) against pathogen infection. These ISR-eliciting microbes can mediate the morphological, physiological and molecular responses of plants. In the last decade, the mechanisms of microbial signals, plant receptors, and hormone signaling pathways involved in the process of PGPR-induced ISR in plants have been well investigated. In this review, plant recognition, microbial elicitors, and the related pathways during plant-microbe interactions are discussed, with highlights on the roles of root hair-specific syntaxins and small RNAs in the regulation of the PGPR-induced ISR in plants.

Corrigendum: Development of plant systemic resistance by beneficial rhizobacteria: Recognition, initiation, elicitation and regulation.

[This corrects the article DOI: 10.3389/fpls.2022.952397.].

Flooding-induced rhizosphere Clostridium assemblage prevents root-to-shoot cadmium translocation in rice by promoting the formation of root apoplastic barriers.

Water managements are the most effective agricultural practices for restraining cadmium (Cd) uptake and translocation in rice, which closely correlated with rhizosphere assembly of beneficial microbiome. However, the role of the assemblage of specific microbiota in controlling root-to-shoot Cd translocation in rice remains scarcely clear. The aim of this study was to ascertain how water managements shaped rhizosphere microbiome and mediated root-to-shoot Cd translocation. To disentangle the acting mechanisms of water managements, we performed an experiment monitoring Cd uptake and transport in rice and changes in soil microbial communities in response to continuously flooding and moistening irrigation. Continuously flooding changed rhizosphere microbial communities, leading to the increased abundance of anaerobic bacteria such as Clostridium populations. Weighted gene co-expression network analysis (WGCNA) showed that a dominant OTU163, corresponding to Clostridium sp. CSP1, exhibited a strong negative correlation with root-to-shoot Cd translocation. An integrated analysis of transcriptome and metabolome further indicated that the Clostridium-secreted butyric acid was involved in the regulation of phenylpropanoid pathway in rice roots. The formation of endodermal suberized barriers and lignified xylems was remarkably enhanced in the Clostridium-treated roots, which led to more Cd retained in root cell wall and less Cd in the xylem sap. Collectively, our results indicate that the development of root apoplastic barriers can be orchestrated by beneficial Clostridium strains that are assembled by host plants grown under flooding regime, thereby inhibiting root-to-shoot Cd translocation.

Fibrinogen like protein-1 knockdown suppresses the proliferation and metastasis of TU-686 cells and sensitizes laryngeal cancer to LAG-3 blockade.

OBJECTIVE: To detect the expression of fibrinogen like protein-1 (FGL-1) in laryngeal cancer and evaluate its effect on tumor proliferation, metastasis, and antitumor immunity. METHODS: ELISA and immunohistochemistry were performed to detect FGL-1 expression in laryngeal cancer. The effects of FGL-1 knockdown on the proliferation, cell cycle progression, apoptosis, migration, and invasion of laryngeal cancer cells were evaluated by the CCK-8, colony formation, flow cytometry, Transwell migration, and western blot assays. We detected changes in tumorigenesis and drug response in vivo following FGL-1 knockdown as well as the effects of anti-LAG3 immunotherapy. Immunohistochemistry was performed to determine CD8 and LAG-3 expression in mouse tumor tissues. RESULTS: FGL-1 was highly expressed in the plasma and tumor tissues of laryngeal cancer patients. FGL-1 knockdown suppressed the proliferation of TU-686 cells and inhibited the migration and invasion of laryngeal cancer by blocking epithelial-to-mesenchymal transition. Moreover, silencing FGL-1 inhibited tumorigenicity in vivo and synergized with anti-LAG3 immunotherapy. CONCLUSIONS: We confirmed the high expression of FGL-1 in laryngeal cancer and identified FGL-1 as a potential marker for immunotherapy in laryngeal cancer.

LncRNA weighted gene co-expression network analysis reveals novel biomarkers related to prostate cancer metastasis.

BACKGROUND: Most prostate cancer patients die from metastasis and lack accurate efficacious biomarkers to monitor the disease behavior, optimize treatment and assess prognosis. Herein, we aimed to identify meaningful lncRNA biomarkers associated with prostate cancer metastatic progression. METHODS: By repurposing microarray probes, 11,624 lncRNAs in prostate cancer were obtained from Gene Expression Omnibus  database (GSE46691, N = 545; GSE29079, N = 235; GSE94767, N = 130). Weighted gene co-expression network analysis was applied to determine the co-expression lncRNA network pertinent to metastasis. Hub lncRNAs were screened. RNA-seq and clinical data from the Cancer Genome Atlas prostate cancer (TCGA-PRAD) cohort (N = 531) were analyzed. Transwell assay and bioinformatic analysis were performed for mechanism research. RESULTS: The high expression levels of nine hub lncRNAs (FTX, AC005261.1, NORAD, LINC01578, AC004542.2, ZFAS1, EBLN3P, THUMPD3-AS1, GAS5) were significantly associated with Gleason score and increased probability of metastatic progression. Among these lncRNAs, ZFAS1 had the consistent trends of expression in all of the analysis from different cohorts, and the Kaplan-Meier survival analyses showed higher expression of ZFAS1 was associated with shorter relapse free survival. In-vitro studies confirmed that downregulation of ZFAS1 decreased prostate cancer cell migration. CONCLUSION: We offered some new insights into discovering lncRNA markers correlated with metastatic progression of prostate cancer using the WGCNA. Some may serve as potential prognostic biomarkers and therapeutic targets for advanced metastatic prostate cancer.

Upregulating hsa-miR-128a Increased the Effects of Pembrolizumab on Laryngeal Cancer Cells via the p53 Pathway.

OBJECTIVES: Recently, immunotherapy and microRNA have shown much more promises in oncology research, inspiring new hope for a cure for various malignancies. Specifically, the function and mechanisms of action of pembrolizumab have been investigated in many cancers, but not in laryngeal squamous cell carcinoma. The present study thus focused on the effect of hsa-miR-128a on pembrolizumab in laryngeal cancer cells as well as tried to elucidate the mechanisms that may mediate this effect. METHODS: Hep2 and AMC-HN8 cell lines were utilized to create stable cell lines that overexpressing hsa-miR-128a. Using the immunotherapy assay, the contribution of hsa-miR-128a to pembrolizumab sensitivity was evaluated. By performing the dual luciferase assay and quantitative real-time polymerase chain reaction, the possible mechanisms of hsa-miR-128a were identified. RESULTS: Hsa-miR-128a was overexpressed in laryngeal cancer cell lines successfully. The immunotherapy assay revealed that upregulating hsa-miR-128a augmented the effect of pembrolizumab. Moreover, hsa-miR-128a targeted BMI-1 and might played a role in the p53 pathway. CONCLUSION: Hsa-miR-128a boosted the effect of pembrolizumab on laryngeal cancer cells, perhaps via the p53 pathway. Therefore, hsa-miR-128a might be a novel target in laryngeal cancer treatment.

Small extracellular vesicle-packaged TGFß1 promotes the reprogramming of normal fibroblasts into cancer-associated fibroblasts by regulating fibronectin in head and neck squamous cell carcinoma.

Tumor development and progression hinge upon ongoing coevolution and crosstalk with the tumor microenvironment. In particular, fibroblasts in the tumor stroma are coopted to support tumor growth and survival through interactions with tumor cells. Despite their significant importance, there is no consensus on the origin of cancer-associated fibroblasts (CAFs) in head and neck squamous cell carcinoma (HNSCC). In this study, we demonstrated that small extracellular vesicle (sEV)-packaged TGFß1 can reprogram normal fibroblasts (NFs) into CAFs both in vitro and in vivo. Mechanistically, TGFß1 in sEV activated NFs by regulating fibronectin, rather than modulating the canonical TGFß-Smad signal pathway. Furthermore, TGFß1 and fibronectin are related to HNSCC clinicopathologic features. Plasma sEV TGFß1 may serve as a potential diagnostic biomarker for HNSCC. This hitherto unknown mechanism of reprogramming of NFs into CAFs by a unique pathway has major implications for underlying cancer-recruited stroma responses.

Diagnostic Significance of Downregulated circMORC3 as a Molecular Biomarker of Hypopharyngeal Squamous Cell Carcinoma: A Pilot Study.

BACKGROUND: Circular RNAs (circRNAs) have proven to be of great clinical significance as diagnostic biomarkers in various cancers. Here, we investigate the expression of circMORC3 in hypopharyngeal squamous cell carcinoma (HSCC), exploring whether it could serve as a diagnostic marker of HSCC. METHODS: CircMORC3 expression levels were detected in HSCC tissues and adjacent normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between circMORC3 expression levels and clinicopathologic factors were explored. CircMORC3 expression levels in plasma from HSCC patients and non-tumor patients were also detected by qRT-PCR. Finally, receiver operating characteristic (ROC) curves were established to evaluate the diagnostic value of circMORC3 as a potential HSCC biomarker in tissues and plasma. RESULTS: The expression levels of circMORC3 were significantly lower in HSCC tissues than paired adjacent normal tissues, and the area under the ROC curve was 0.834. The decreased expression of circMORC3 was correlated to T stages and tumor sizes. Similarly, the circMORC3 expression levels in HSCC patient plasma were lower than non-tumor patient plasma, and the area under the ROC curve was 0.767. CONCLUSION: Our results indicate that circMORC3 was downregulated in HSCC tissues and plasma, and it could serve as an early diagnostic HSCC biomarker.

The role of long non-coding RNA HOTAIR in the progression and development of laryngeal squamous cell carcinoma interacting with EZH2.

CONCLUSIONS: The aberrant expression of long non-coding RNA HOTAIR and transmethylase EZH2 played important roles in the progression and development of laryngeal squamous cell carcinoma (LSCC). OBJECTIVES: This research was aimed to explore the expression and correlation with clinicopathological characteristics of HOTAIR and EZH2 in LSCC, and to evaluate the function of the two in regulating the proliferation and cis-platinum resistance processes of LSCC. METHODS: Quantitative real time-PCR (qPCR) was conducted to measure the expression of HOTAIR and EZH2 in tissue samples. Clinicopathological features were collected and statistically analyzed combining with the expression of HOTAIR and EZH2. The variance of EZH2 with down-regulating HOTAIR was measured by qPCR. CCK-8 proliferation test was conducted to detect the proliferation feature in LSCC cells. After cultured with a series of cis-platinum concentrations for 24 h, cell viability was detected using CCK-8 assay, and the inhibition rates were calculated. RESULTS: HOTAIR and EZH2 were over-expressed in LSCC tissue. The higher expression was significantly related to T phase, pathological grades, and risk of lymphatic metastasis of LSCC. Suppressing HOTAIR expression stimulated EZH2 expressing, promoted the proliferation of AMC-HN8 cells, and increased the sensitivity to cis-platinum of the LSCC cells.

Effect of multidrug resistance 1/P-glycoprotein on the hypoxia-induced multidrug resistance of human laryngeal cancer cells.

In a previous study, it was demonstrated that hypoxia upregulated the multidrug resistance (MDR) of laryngeal cancer cells to chemotherapeutic drugs, with multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp) expression also being upregulated. The present study aimed to investigate the role and mechanism of MDR1/P-gp on hypoxia-induced MDR in human laryngeal carcinoma cells. The sensitivity of laryngeal cancer cells to multiple drugs and cisplatin-induced apoptosis was determined by CCK-8 assay and Annexin-V/propidium iodide staining analysis, respectively. The accumulation of rhodamine 123 (Rh123) in the cells served as an estimate of drug accumulation and was evaluated by flow cytometry (FCM). MDR1/P-gp expression was inhibited using interference RNA, and the expression of the MDR1 gene was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. As a result, the sensitivity to multiple chemotherapeutic agents and the apoptosis rate of the hypoxic laryngeal carcinoma cells increased following a decrease in MDR1/P-gp expression (P<0.05). Additionally, FCM analysis of fluorescence intensity indicated that the downregulated expression of MDR1/P-gp markedly increased intracellular Rh123 accumulation (P<0.05). Such results suggest that MDR1/P-gp serves an important role in regulating hypoxia-induced MDR in human laryngeal carcinoma cells through a decrease in intracellular drug accumulation.

EZH2 is overexpressed in laryngeal squamous cell carcinoma and enhances the stem-like properties of AMC-HN-8 cells.

The enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) histone methyltransferase is the catalytic subunit of polycomb repressive complex 2 (PRC2), which is important for epigenetic regulation. EZH2 is highly expressed in various types of tumors, and its high-level expression promotes the progression and invasion of certain tumors. However, the expression level of EZH2 and its functions in laryngeal squamous cell carcinomas are unknown. In the present study, the level of EZH2 expression in laryngeal squamous cell carcinomas was evaluated using immunochemical staining and reverse transcription-quantitative polymerase chain reaction. EZH2 was overexpressed in AMC-HN-8 cells with lentiviral transfection. Cell proliferation, apoptosis, cell-cycle, chemotherapy-sensitivity and in vivo tumorigenic assays were performed. The results indicated that EZH2 was highly expressed in laryngeal squamous cell carcinomas. Additionally, EZH2 overexpression promoted proliferation, accelerated cell-cycle progression and enhanced the tumorigenicity in laryngeal squamous cancer cells. More importantly, EZH2 enhanced the chemotherapy resistance of these cells. Overall, the results indicated that EZH2 promotes the progression of laryngeal squamous cell cancer and could be a potential chemotherapeutic target for the treatment of such cancer.

Cisplatin and paclitaxel target significant long noncoding RNAs in laryngeal squamous cell carcinoma.

The objectives of this study were to identify specific long noncoding RNAs (lncRNAs) in laryngeal squamous cell carcinoma (LSCC) and to clarify the function of cisplatin and paclitaxel on the confirmed laryngeal cancer lncRNAs. Fifty-four pairs of laryngeal tumor and adjacent normal tissue were collected. Candidate lncRNAs were searched in authorized databases. The significant lncRNAs were identified and confirmed through high-output real-time PCR. Chemotherapy assay evaluated the influences of cisplatin and paclitaxel on the significant lncRNAs. Thirty-seven cancer-related candidate lncRNAs were selected. Three up-expressed and two down-expressed significant lncRNAs were identified and confirmed. The expressions of lncRNA CDKN2B-AS1, HOTAIR and MALAT1 were dramatically reduced with the increasing concentration of cisplatin and paclitaxel and also lengthening of the treatment duration. Cisplatin and paclitaxel have target function on significant lncRNAs in LSCC, which presents novel molecular targets to cure LSCC patients and also leads an orientation for developing new drugs.