Search

Abstract Background Microtubule‐targeing agents (MTAs), such as paclitaxel (PTX) and vincristine (VCR), kill cancer cells through activtion of the spindle assembly checkpoint (SAC) and induction of mitotic arrest, but the development of resistance poses significant clinical challenges. Methods Immunoblotting and RT‐qPCR were used to investigate potential function and related mechanism of MORC2. Flow cytometry analyses were carried out to determine cell cycle distribution and apoptosis. The effect of MORC2 on cellular sensitivity to PTX and VCR was determined by immunoblotting, flow cytometry, and colony formation assays. Immunoprecipitation assays and immunofluorescent staining were utilized to investigate protein‐protein interaction and protein co‐localization. Results Here, we identified microrchidia family CW‐type zinc finger 2 (MORC2), a poorly characterized oncoprotein, as a novel regulator of SAC activation, mitotic progression, and resistance of cancer cells to PTX and VCR. Mechanically, PTX and VCR activate cyclin‐dependent kinase 1, which in turn induces MORC2 phosphorylation at threonine 717 (T717) and T733. Phosphorylated MORC2 enhances its interation with HSPA8 and LAMP2A, two essential components of the chaperone‐mediated autophagy (CMA) mechinery, resulting in its autophagic degradation. Degradation of MORC2 during mitosis leads to SAC activation through stabilizing anaphase promoting complex/cyclosome activator protein Cdc20 and facilitating mitotic checkpoint complex assembly, thus contributing to mitotic arrest induced by PTX and VCR. Notably, knockdown of MORC2 promotes mitotic arrest induced by PTX and VCR and enhances the sensitivity of cancer cells to PTX and VCR. Conclusions Collectively, these findings unveil a previously unrecognized function and regulatory mechanism of MORC2 in mitotic progression and resistance of cancer cells to MTAs. These results also provide a new clue for developing combined treatmentstrategy by targeting MORC2 in combination with MTAs against human cancer.

Background and objectiveThe CHOICE-01 trial showed that toripalimab plus chemotherapy achieved satisfactory outcomes compared with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who were negative for driver genes, but the economics of this regimen is unclear. Therefore, this study aimed to evaluate the cost-effectiveness of toripalimab in combination with chemotherapy in advanced NSCLC with negative driver genes from the perspective of the Chinese healthcare system.Materials and methodsA three-state partitioned survival model was developed to simulate the costs and outcomes associated with adding toripalimab to first-line chemotherapy. The clinical data in the model came from the CHOICE-01 trial, only direct medical costs were included, and utility values were referred to the literature. Four models were applied to explore the differences in the results of fitting and extrapolating K-M curves from different models, and cost-effectiveness subgroup analysis was performed. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the impact of parameter uncertainty on the model.ResultsThe baseline analysis showed that toripalimab coupled with chemotherapy cost $21,052 more than chemotherapy ($43,197 vs. $22,145) and also gained 0.71 QALYs more (1.75 QALYs vs. 1.03 QALYs), with an ICER of $29,478/QALYs. At the current willingness-to-pay threshold ($35,108/QALY), the extra cost was well worth it. The results of fitting and extrapolating the survival curves using other models were consistent with the results of the standard parametric model. Subgroup analysis demonstrated that the addition of toripalimab to chemotherapy was economical. Sensitivity analysis showed that the utility values of PD and PFS stages had the greatest impact on the model.ConclusionFrom the viewpoint of the Chinese healthcare system, toripalimab combined with chemotherapy in the treatment of advanced NSCLC with negative driver genes was likely to be cost-effective compared with chemotherapy.

The rare earth conversion film has attracted more and more attention in recent years because of its good corrosion resistance and non - toxicity. The concept and film forming mechanism of rare earth conversion film were briefly introduced, and the application of rare earth in corrosion prevention for ferrous metals as well as the nonferrous metals of aluminum, magnesium, zinc and their alloys was summarized. This study found that the corrosion resistance of composite rare earth conversion film was better than that of the single rare earth conversion film. Moreover, it also explained the reason why cerium conversion film had better corrosion resistance than other rare earth conversion films. Finally, it pointed out that the composite rare earth conversion film, rare earth composite alloy coating and densification of rare earth conversion film would be the development direction.

Abstract As global aging accelerates, the prevention and treatment of age-related bone diseases are becoming a critical issue. In the process of senescence, bone marrow mesenchymal stem cells (BMSCs) gradually lose the capability of self-renewal and functional differentiation, resulting in impairment of bone tissue regeneration and disorder of bone tissue homeostasis. Alteration in epigenetic modification is an essential factor of BMSC dysfunction during aging. Its transferability and reversibility provide the possibility to combat BMSC aging by reversing age-related modifications. Emerging evidence demonstrates that epigenetic therapy based on aberrant epigenetic modifications could alleviate the senescence and dysfunction of stem cells. This review summarizes potential therapeutic targets for BMSC aging, introduces some potential approaches to alleviating BMSC aging, and analyzes its prospect in the clinical application of age-related bone diseases.

Abstract Background Experiencing internship shapes nursing students’ professional commitment and aggravates its changes. However, few studies have been investigated how this changes empirically. Objectives The aims of this study are to investigate (a) what are the changes of professional commitment of nursing students before and after the internship? (b) Which of multiple independent variables is the strongest predictor? Methods A longitudinal study was conducted with 996 senior undergraduate nursing students (ready to enter clinical practice) in the China universities. The survey was conducted in the spring of 2015 and autumn of 2016. The data were collected by a paper-and-pencil questionnaire. The instruments used included Professional Commitment Scale and Perceived Stress Scale. Analysis of paired t-test and linear regression analysis were performed on the data. Results Nursing students showed lower professional commitment (2.79 ± 0.36) than they were (2.92 ± 0.36) before internship. Socio-demographic variables, pre-internship professional commitment and stress perceived during internship predicted 40.1% of the variance in the post-internship commitment. Discussion These data summarize the nursing students’ professional commitment changes and the main influential factors that contribute to post-internship professional commitment of undergraduate nursing student. The findings are timely, which indicate that senior nursing students’ professional commitment can be increased by enhancing pre-internship commitment and reducing students’ stress levels during internship.

Abstract Triple-negative breast cancer (TNBC) is a highly lethal disease due to aggressive clinical phenotype and the lack of validated therapeutic targets. Our recent quantitative proteomic analysis of 90 cases of TNBC tissues and 72 cases of matched adjacent normal tissues revealed that the expression levels of BPTF-associated protein of 18 KDa (BAP18), a component of the MLL1 and NURF chromatin complexes, were upregulated in TNBC tissues relative to normal tissues. However, the biological function and the underlying mechanism of BAP18 in TNBC progression remain unexplored. Here, we report that BAP18 promoted TNBC cell proliferation, migration, and invasion in vitro and xenograft tumor growth and lung colonization in vivo. Mechanistic investigations revealed that S100 calcium-binding protein A9 (S100A9), a member of the S100 protein family that is frequently upregulated in breast tumors and acts as an oncogenic driver in breast cancer progression, was a downstream target gene of BAP18. BAP18 was recruited to histone H3 trimethylation at lysine 4 (H3K4me3)-marked promoter of S100A9 and enhanced its promoter activities. Notably, knockdown of BAP18 by short hairpin RNA in TNBC cells suppressed xenograft tumor growth in mice, the noted effect was partially reverted by re-expression of S100A9 in BAP18-depleted cells. Taken together, these results suggest that BAP18 promotes TNBC progression through, at least in part, transcriptional activation of oncogene S100A9, and represents a potential therapeutic target for TNBC.

Triple-negative breast cancer (TNBC) is the most fatal subtype of breast cancer; however, effective treatment strategies for TNBC are lacking. Therefore, it is important to explore the mechanism of TNBC metastasis and identify its therapeutic targets. Dysregulation of ETHE1 leads to ethylmalonic encephalopathy in humans; however, the role of ETHE1 in TNBC remains elusive. Stable cell lines with ETHE1 overexpression or knockdown were constructed to explore the biological functions of ETHE1 during TNBC progression in vitro and in vivo. Mass spectrometry was used to analyze the molecular mechanism through which ETHE1 functions in TNBC progression. ETHE1 had no impact on TNBC cell proliferation and xenograft tumor growth but promoted TNBC cell migration and invasion in vitro and lung metastasis in vivo. The effect of ETHE1 on TNBC cell migratory potential was independent of its enzymatic activity. Mechanistic investigations revealed that ETHE1 interacted with eIF2α and enhanced its phosphorylation by promoting the interaction between eIF2α and GCN2. Phosphorylated eIF2α in turn upregulated the expression of ATF4, a transcriptional activator of genes involved in cell migration and tumor metastasis. Notably, inhibition of eIF2α phosphorylation through ISRIB or ATF4 knockdown partially abolished the tumor-promoting effect of ETHE1 overexpression. ETHE1 has a functional and mechanistic role in TNBC metastasis and offers a new therapeutic strategy for targeting ETHE1-propelled TNBC using ISRIB.

Interference with quorum sensing (QS) represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance. Over the past two decades, a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors (QSIs) have a strong impact on the discovery of anti-infective drugs against various types of bacteria. The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents. For the discovery of QSIs, diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems. This review highlights the latest findings in strategies and methodologies for QSI screening, involving activity-based screening with bioassays, chemical methods to seek bacterial QS pathways for QSI discovery, virtual screening for QSI screening, and other potential tools for interpreting QS signaling, which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.

In this paper, a two-stage equalization topology based on Zero-Voltage Switching Quasi-Resonant Converter (ZVS QRC) is proposed to solve the problems of long equalization time and low energy utilization of series lithium-ion battery packs. The equalization topology is divided into two forms: intra-group and inter-group, ZVS QRCs are adopted in both intra-group and inter-group, which can equalize any single cell within a group, and the equalization circuit within each pack can equalize simultaneously, which greatly reduces the equalization time, and reduces the switching loss during the equalization process by introducing quasi-resonant circuit to improve the energy utilization. Taking the State of Charge (SOC) as the equalization target, a group equalization strategy based on the Credibility Factor (C-F) inference model is proposed. The strategy defines the SOC unbalance degree of a single battery, gets the group unbalance degree according to the C-F inference model, and gets the group equalization state from the unbalance degree, to control the group for equalization. Matlab/Simulink software is used to build the model and simulate it. The experimental results demonstrate that the proposed topology saves approximately 25% of the equalization time compared to the traditional Buck-Boost group equalization topology. Under the same static and charge/discharge conditions, the equalization time is reduced by about 21% and the energy utilization is improved by about 6% after using the C-F inference model for equalization compared to the fixed-threshold method.

ABSTRACT Small RNAs (sRNAs) play a very important role in gene regulation at the posttranscriptional level. However, sRNAs from nonmodel microorganisms, extremophiles in particular, have been rarely explored. We discovered a putative sRNA, termed Pf1 sRNA, in Pseudoalteromonas fuliginea BSW20308 isolated from the polar regions in our previous work. In this study, we identified the sRNA and investigated its regulatory role in gene expression under different temperatures. Pf1 sRNA was confirmed to be a new member of the CsrB family but has little sequence similarity with Escherichia coli CsrB. However, Pf1 sRNA was able to bind to CsrA from E. coli and P. fuliginea BSW20308 to regulate glycogen synthesis. The Pf1 sRNA knockout strain (ΔPf1) affected motility, fitness, and global gene expression in transcriptomes and proteomes at 4°C and 32°C. Genes related to carbon metabolism, amino acid metabolism, salinity tolerance, antibiotic resistance, oxidative stress, motility, chemotaxis, biofilm, and secretion systems were differentially expressed in the wild-type strain and the ΔPf1 mutant. Our study suggested that Pf1 sRNA might play an important role in response to environmental changes by regulating global gene expression. Specific targets of the Pf1 sRNA-CsrA system were tentatively proposed, such as genes involved in the type VI secretion system, TonB-dependent receptors, and response regulators, but most of them have an unknown function. Since this is the first study of CsrB family sRNA in Pseudoalteromonas and microbes from the polar regions, it provides a novel insight at the posttranscriptional level into the responses and adaptation to temperature changes in bacteria from extreme environments. This study also sheds light on the evolution of sRNA in extreme environments and expands the bacterial sRNA database. IMPORTANCE Previous research on microbial temperature adaptation has focused primarily on functional genes, with little attention paid to posttranscriptional regulation. Small RNAs, the major posttranscriptional modulators of gene expression, are greatly underexplored, especially in nonpathogenic and nonmodel microorganisms. In this study, we verified the first Csr sRNA, named Pf1 sRNA, from Pseudoalteromonas, a model genus for studying cold adaptation. We revealed that Pf1 sRNA played an important role in global regulation and was indispensable in improving fitness. This study provided us a comprehensive view of sRNAs from Pseudoalteromonas and expanded our understanding of bacterial sRNAs from extreme environments.

Electrochemistry is a promising approach to make existing chemical protocols milder, but many simple transformations of feedstocks are still out of reach. Here, the authors transform unactivated aryl and alkyl (pseudo)halides into carboxylic acids, via nickel catalysis and electricity, using atmospheric CO2 as the carbon source.

The establishment of effective vascularization represents a key challenge in regenerative medicine. Adequate sources of vascular cells and intact vessel fragments have not yet been explored. We herein examined the potential application of microvessels induced from hiPSCs for rapid angiogenesis and tissue regeneration. Microvessels were generated from human pluripotent stem cells (iMVs) under a defined induction protocol and compared with human adipose tissue-derived microvessels (ad-MVs) to illustrate the similarity and differences of the alternative source. Then, the therapeutic effect of iMVs was detected by transplantation in vivo. The renal ischemia-reperfusion model and skin damage model were applied to explore the potential effect of vascular cells derived from iMVs (iMVs-VCs). Besides, the subcutaneous transplantation model and muscle injury model were established to explore the ability of iMVs for angiogenesis and tissue regeneration. The results revealed that iMVs had remarkable similarities to natural blood vessels in structure and cellular composition, and were potent for vascular formation and self-organization. The infusion of iMVs-VCs promoted tissue repair in the renal and skin damage model through direct contribution to the reconstruction of blood vessels and modulation of the immune microenvironment. Moreover, the transplantation of intact iMVs could form a massive perfused blood vessel and promote muscle regeneration at the early stage. The infusion of iMVs-VCs could facilitate the reconstruction and regeneration of blood vessels and modulation of the immune microenvironment to restore structures and functions of damaged tissues. Meanwhile, the intact iMVs could rapidly form perfused vessels and promote muscle regeneration. With the advantages of abundant sources and high angiogenesis potency, iMVs could be a candidate source for vascularization units for regenerative medicine.

ObjectiveTo evaluate the economics of sugemalimab plus chemotherapy in the first-line treatment of metastatic non-small cell lung cancer, and to provide a reference for the formulation of relevant medical insurance policies and rational drug use.MethodsFrom the perspective of the Chinese health system, a three-state partitioned survival model was constructed based on data from a phase III randomized clinical trial (GEMSTONE 302) to evaluate the cost-utility of sugemalimab plus chemotherapy compared with chemotherapy in first-line treatment of metastatic non-small cell lung cancer. Model results were expressed as total cost, life years, quality-adjusted life years, and incremental cost-effectiveness ratio. The robustness of the underlying analysis results was verified using one-way sensitivity analysis and probabilistic sensitivity analysis.ResultsThe results of the base-case analysis showed that sugemalimab plus chemotherapy yielded 1.63 QALYs at a total cost of 130,667.70 USD, chemotherapy yielded 1.04 QALYs at a total cost of 64,001.02 USD, and the ICER was 113,155.52 USD/QALY, which was well above the current willingness-to-pay threshold in China (3 times 2021 per capita GDP) (36,203.88 USD).ConclusionThis study suggests that sugemalimab in combination with a chemotherapy regimen is more effective but not economical for patients with metastatic non-small cell lung cancer receiving first-line therapy in China and that a reasonable reduction in drug prices could improve the probability of it being economical.

Background and purpose: 18 F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography and computed tomography (PET/CT) is an advanced molecular imaging evaluation method for prostate cancer (PCa). This study aimed to explore the early detection rate of recurrence and metastasis of patients with biochemical recurrence (BCR) after radical prostatectomy (RP) by 18 F-PSMA-1007 PET/CT and its influence on clinical treatment decisions. Methods: From December 2018 to December 2020, the data of 51 PCa patients with BCR after RP by 18 F-PSMA-1007 PET/CT were summarized and analyzed. Radioactive uptake of tumors was calculated semi-quantitatively by region of interest method and expressed by the maximum standardized uptake value (SUV max ). We assessed the detection rate of clinical recurrence and metastasis in BCR patients [local recurrence (prostatic bed), lymph node metastasis (pelvic, retroperitoneal and diaphragmatic), bone metastasis and visceral metastasis (such as lung)], and the difference in detection rate between prostate-specific antigen (PSA) groups and Gleason evaluation group was further compared respectively. Results: The median age of 51 patients was 66 years (52-80 years), and the median PSA was 35 ng/mL (6-224 ng/mL) at the time of initial diagnosis. All of them were prostatic acinar adenocarcinoma, including 1 case with intraductal carcinoma, 1 case with ductal adenocarcinoma, 1 case with mucinous adenocarcinoma, 1 case with signet ring-like component and 1 case with neuroendocrine differentiation. We found Gleason score ≤7 in 22 cases (43.14%) and Gleason score ≥ 8 in 29 cases (56.86%). The median time of BCR was 15 months (5-62 months), and the median PSA was 0.58 ng/mL (0.20- 110.00 ng/mL), including 21 (41.18%) cases with 0.20 ng/mL≤PSA ＜ 0.50 ng/mL, 12 (23.53%) cases with 0.50 ng/mL≤PSA ＜ 1.00 ng/mL, 4 (7.84%) cases with 1.00 ng/mL≤PSA ＜ 2.00 ng/mL and 14 (27.45%) cases with PSA≥2.00 ng/mL. There were 7 cases (13.73%) with no local recurrence or metastasis, and 44 cases (86.27%) with local recurrence or metastasis, including 9 cases (20.45%) with recurrence in the operative area of prostate, 28 cases (63.64%) had lymph node metastasis at different sites, 31 cases (70.45%) had bone metastasis, and 2 cases (4.55%) had visceral metastasis. In addition, there were 2 cases of subcutaneous nodule metastasis and 1 case of penile root metastasis. The median SUV max was 17.9 (1.4-110.9) for all recurrence or metastasis, 14.0 (3.2-110.9) for local recurrence, 10.2 (2.0-90.1) for lymph node metastasis, and 5.4 (1.4-109.6) for bone metastasis. The detection rates of recurrence or metastasis were 71.43% (15/21), 100.00% (12/12), 75.00% (3/4) and 100.00% (14/14), respectively, in the groups with 0.20 ng/mL≤PSA ＜ 0.50 ng/mL (21 cases), 0.50 ng/mL≤PSA ＜ 1.00 ng/mL (12 cases), 1.00 ng/mL≤PSA ＜ 2.00 ng/mL (4 cases) and PSA≥2.00 ng/mL (14 cases), and there was no statistically significant difference in the detection rate between groups with different PSA levels (P＞0.05). The recurrence or metastasis detection rates of original Gleason score ≤7 group (22 cases) and Gleason score ≥8 group (29 cases) were 68.18% (15/22) and 100.00% (29/29), respectively, and there were statistically significant differences in the detection rate between groups with different Gleason scores (P ＜ 0.05). In clinical treatment, 4 cases (7.84%) were treated by observation, 18 cases (35.29%) by endocrinotherapy alone, 2 cases (3.92%) by salvage radiotherapy (SRT) alone, 24 cases (47.06%) by endocrinotherapy combined with SRT, 1 case (1.96%) by endocrinotherapy combined with docetaxel systemic chemotherapy, and 2 cases (3.92%) by salvage pelvic lymphadenectomy. Conclusion: 18 F-PSMA-1007 PET/CT has a good value and efficacy in early diagnosis of clinical recurrence or metastasis of BCR patients after RP, which is conducive to accurate evaluation and optimal treatment plan for such patients, and significantly affects clinical treatment decisions.

AIM: To use spectral domain optical coherence tomography(SD-OCT)to measure macular subfoveal choroid thickness(SFCT)in patients with diabetic retinopathy(DR), observe the changes of SFCT, and to explore the relationship between SFCT and diabetes mellitus and diabetes retinopathy.METHODS: A total of 152 patients with type 2 diabetes(T2DM)were collected and grouped according to their fundus conditions. There were 72 cases in the NDR group and 80 cases in the DR group. Eighty-five healthy subjects were used as the control group. Follow-up according to the clinical stage of DR, where the DR components were mild NPDR, moderate NPDR, severe NPDR and PDR. According to the United Nations World Health Organization, the age group was divided into three age groups: 18-44 years old(youth group), 45-59 years old(middle-aged group), and 60-75 years old(old group). Analyzed and compared the SFCT between each group.RESULTS:There was no statistically significant difference in SFCT between the T2DM group and the control group(P>0.05). The SFCT of the all group was not significantly correlated with age and course of disease(P>0.05); the SFCT of the control group was negatively correlated with age(P0.05). The SFCT of the T2DM group was thinner than the control group(P

Abstract Background Inference of protein’s membership in metabolic pathways has become an important task in functional annotation of protein. The membership information can provide valuable context to the basic functional annotation and also aid reconstruction of incomplete pathways. Previous works have shown success of inference by using various similarity measures of gene ontology. Results In this work, we set out to explore integrating ontology and sequential information to further improve the accuracy. Specifically, we developed a neural network model with an architecture tailored to facilitate the integration of features from different sources. Furthermore, we built models that are able to perform predictions from pathway-centric or protein-centric perspectives. We tested the classifiers using 5-fold cross validation for all metabolic pathways reported in KEGG database. Conclusions The testing results demonstrate that by integrating ontology and sequential information with a tailored architecture our deep neural network method outperforms the existing methods significantly in the pathway-centric mode, and in the protein-centric mode, our method either outperforms or performs comparably with a suite of existing GO term based semantic similarity methods.

Seashore paspalum (Paspalum vaginatum) is a halophytic, warm-season grass which is closely related to various grain crops. Gene duplication plays an important role in plant evolution, conferring significant plant adaptation at the genomic level. Here, we identified 2,542 tandem duplicated genes (TDGs) in the P. vaginatum genome and estimated the divergence time of pairs of TDGs based on synonymous substitution rates (Ks). Expression of P. vaginatum TDGs resulted in enrichment in many GO terms and KEGG pathways when compared to four other closely-related species. The GO terms included: “ion transmembrane transporter activity,” “anion transmembrane transporter activity” and “cation transmembrane transport,” and KEGG pathways included “ABC transport.” RNA-seq analysis of TDGs showed tissue-specific expression under salt stress, and we speculated that P. vaginatum leaves became adapted to salt stress in the earlier whole-genome duplication (WGD; ~83.3 million years ago; Ma), whereas the entire P. vaginatum plant acquired a large number of TDGs related to salt stress in the second WGD (~23.3 Ma). These results can be used as a reference resource to accelerate salt-resistance research in other grasses and crops.

Abstract Background The biofilm state of pathogens facilitates antimicrobial resistance which makes difficult-to-treat infections. In this regard, it has been found that the compounds screened from plant extracts represent one category of the most promising antibiofilm agents. However, the antibiofilm activities and the active ingredients of plant extracts remain largely unexplored. In this background, the study is (1) to screen out the plant extracts with antibiofilm ability against Pseudomonas aeruginosa, and (2) to identify the active ingredients in the plant extracts and elucidate the underlying mechanism of the antibiofilm activities. Methods Micro-broth dilution method, in vitro biofilm model, LC–MS/MS analysis and P. aeruginosa-mouse infection model were adopted to assess the antibiofilm activity. GC–MS analysis was performed to detect the active ingredients in plasma. RNA-Seq, GO analysis, KEGG analysis and RT-qPCR were adopted to elucidate the underlying mechanism of antibiofilm activities against P. aeruginosa. Results Lonicerae Japonicae Flos (LJF) among 13 plants could exert significant inhibitory effects on bacterial biofilm formation, mobility and toxin release in vitro, and it could exert antibiofilm effect in vivo too. Moreover, quinic acid, as one metabolite of chlorogenic acid, was found as an active ingredient in LJF against the biofilm of P. aeruginosa. The active ingredient significantly inhibited EPS secretion in biofilm formation and maturity and could achieve synergistic antibiofilm effect with levofloxacin. It reduced the biofilm formation by regulating core targets in quorum sensing system. In GO process, it was found that the core targets were significantly enriched in multiple biological processes involving locomotion, chemotaxis and motility mediated by flagellum/cilium, which was related to KEGG pathways such as bacterial chemotaxis, oxidative phosphorylation, ribosome, biofilm formation, cyanoamino acid metabolism and quorum sensing. Finally, the binding of quinic acid with core targets rhlA, rhlR and rhlB were validated by molecular docking and RT-qPCR. Conclusions In summary, the study verified the in vitro and in vivo antibiofilm effects of LJF against P. aeruginosa and elucidated the active ingredients in LJF and its conceivable pharmacological mechanism, indicating that quinic acid could have the potential of an antibiofilm agent against P. aeruginosa and related infections. Graphic abstract

Compounds bearing a carbonyl group, such as aldehydes and ketones, are important industrial chemicals and widespread in pharmaceuticals and natural products. Here, the authors report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO2, to generate valuable α-hydroxycarboxylic acids.

N6-methyladenine (6mA) DNA modification has been detected in several eukaryotic organisms, in some of them, it plays important role in the regulation process of stress-resistance response. However, the genome-wide distribution patterns and potential functions of 6mA DNA modification in halophyte Seashore paspalum (Paspalum vaginatum) remain largely unknown. Here, we examined the 6mA landscape in the P. vaginatum genome by adopting single molecule real-time sequencing technology and found that 6mA modification sites were broadly distributed across the P. vaginatum genome. We demonstrated distinct 6mA methylation levels and 6mA distribution patterns in different types of transcription genes, which hinted at different epigenetic rules. Furthermore, the moderate 6mA density genes in P. vaginatum functionally correlated with stress resistance, which also maintained a higher transcriptional level. On the other hand, a specific 6mA distribution pattern in the gene body and near TSS was observed in gene groups with higher RNA expression, which maybe implied some kind of regularity between 6mA site distribution and the protein coding genes transcription was possible. Our study provides new insights into the association between 6mA methylation and gene expression, which may also contribute to key agronomic traits in P. vaginatum.

Impatiens wutaishanensis R.L. Liao & Lei Cai, a new species from Southeast Yunnan, China, is here described and illustrated. This new species is most similar to Impatiens parvisepala S.X. Yu & Y.T. Hou in its racemose inflorescences, its four lateral sepals, the leaf arrangement, and in having yellow flowers. However, it differs in the height of the plants, the length of the petiole, the size and shape of the leaf blade, the shape of the spur, and the number of flowers in each inflorescence. A detailed description, color photographs, and a provisional IUCN red list assessment are provided, and its geographical distribution, ecology, and morphological relationship with relevant similar species are discussed.

AIM: To describe the clinical features of acute myopic onset of optic neuropathy and observe the effects of retrobulbar and systemic glucocorticoid therapy in a real-world setting. METHODS: A retrospective observational case series included 18 patients with a clinical diagnosis of acute onset of myopic optic neuropathy in a real-world setting. While the patients were using retrobulbar and systemic glucocorticoid therapy, various imaging examination data were analysed, and the clinical features of myopic optic neuropathy were summarized for 6mo to 2y. RESULTS: The included group of patients with acute onset of myopic optic neuropathy consisted mostly of females (n=11). The visual field (VF) showed abnormalities in bilateral eyes, including the spread of physiological blind spots, central and paracentral dark spots, and centripetal peripheral VF reduction; but central vision with no subjective changes. The visual evoked potential (VEP) was abnormal in all eyes with vision loss. The best corrected visual acuity (BCVA) was improved from 1.04±0.63 to 0.47±0.57 (logMAR) after glucocorticoid treatment (P0.05). There was no recurrence during long-term follow-up observation. CONCLUSION: The acute onset of myopic optic neuropathy is characterized by BCVA and VF abnormalities in bilateral eyes. Retrobulbar and systemic glucocorticoid therapy is effective.

Abstract Background The low survival rate or dysfunction of extracellular matrix (ECM)-based engineered organs caused by the adverse effects of unfavourable local microenvironments on seed cell viability and stemness, especially the effects of excessive reactive oxygen species (ROS), prompted us to examine the importance of controlling oxidative damage for tissue transplantation and regeneration. We sought to improve the tolerance of seed cells to the transplant microenvironment via antioxidant pathways, thus promoting transplant efficiency and achieving better tissue regeneration. Methods We improved the antioxidative properties of ECM-based bioroots with higher glutathione contents in dental follicle stem cells (DFCs) by pretreating cells or loading scaffolds with the antioxidant NAC. Additionally, we developed an in situ rat alveolar fossa implantation model to evaluate the long-term therapeutic effects of NAC in bioroot transplantation. Results The results showed that NAC decreased H2O2-induced cellular damage and maintained the differentiation potential of DFCs. The transplantation experiments further verified that NAC protected the biological properties of DFCs by repressing replacement resorption or ankylosis, thus facilitating bioroot regeneration. Conclusions The following findings suggest that NAC could significantly protect stem cell viability and stemness during oxidative stress and exert better and prolonged effects in bioroot intragrafts.

Abstract Background Hidden Markov models (HMM) are a powerful tool for analyzing biological sequences in a wide variety of applications, from profiling functional protein families to identifying functional domains. The standard method used for HMM training is either by maximum likelihood using counting when sequences are labelled or by expectation maximization, such as the Baum–Welch algorithm, when sequences are unlabelled. However, increasingly there are situations where sequences are just partially labelled. In this paper, we designed a new training method based on the Baum–Welch algorithm to train HMMs for situations in which only partial labeling is available for certain biological problems. Results Compared with a similar method previously reported that is designed for the purpose of active learning in text mining, our method achieves significant improvements in model training, as demonstrated by higher accuracy when the trained models are tested for decoding with both synthetic data and real data. Conclusions A novel training method is developed to improve the training of hidden Markov models by utilizing partial labelled data. The method will impact on detecting de novo motifs and signals in biological sequence data. In particular, the method will be deployed in active learning mode to the ongoing research in detecting plasmodesmata targeting signals and assess the performance with validations from wet-lab experiments.

We numerically and experimentally investigated the behavior of high-frequency underwater ultrasounds reflected by gradient acoustic metasurfaces. Metasurfaces were fabricated with a periodic array of gradient slits along the surface of a steel specimen. The finite element method was adopted for the acoustics–structure interaction problem to design the metasurfaces and simulate the reflected fields of the incident ultrasound. Our metasurfaces yielded anomalous reflection, specular reflection, apparent negative reflection, and radiation of surface-bounded modes for ultrasonic waves impinging on the metasurfaces at different incident angles. The occurrence of these reflection behaviors could be explained by the generalized Snell’s law for a gradient metasurface with periodic supercells. We showed that at some incident angles, strong anomalous reflection could be generated, which could lead to strong retroreflection at specific incident angles. Furthermore, we characterized the time evolution of the reflections using pulsed ultrasound. The simulated transient process revealed the formation of propagating reflected ultrasound fields. The experimentally measured reflected ultrasound signals verified the distinct reflection behaviors of the metasurfaces; strong anomalous reflection steering the ultrasound pulse and causing retroreflection was observed. This study paves the way for designing underwater acoustic metasurfaces for ultrasound imaging and caustic engineering applications using pulsed ultrasound in the high-frequency regime.

The Qinghai-Tibet Plateau is rich in renewable solar energy resources. Under the background of China’s “dual-carbon” strategy, it is of great significance to develop a global horizontal irradiation (GHI) prediction model suitable for Tibet. In the radiation balance budget process of the Earth-atmosphere system, clouds, aerosols, air molecules, water vapor, ozone, CO2 and other components have a direct influence on the solar radiation flux received at the surface. For the descending solar shortwave radiation flux in Tibet, the attenuation effect of clouds is the key variable of the first order. Previous studies have shown that using Artificial intelligence (AI) models to build GHI prediction models is an advanced and effective research method. However, regional localization optimization of model parameters is required according to radiation characteristics in different regions. This study established a set of AI prediction models suitable for Tibet based on ground-based solar shortwave radiation flux observation and cloud cover observation data of whole sky imaging in the Yangbajing area, with the key parameters sensitively tested and optimized. The results show that using the cloud cover as a model input variable can significantly improve the prediction accuracy, and the RMSE of the prediction accuracy is reduced by more than 20% when the forecast horizon is 1 h compared with a model without the cloud cover input. This conclusion is applicable to a scenario with a forecast horizon of less than 4 h. In addition, when the forecast horizon is 1 h, the RMSE of the random forest and long short-term memory models with a 10-min step decreases by 46.1% and 55.8%, respectively, compared with a 1-h step. These conclusions provide a reference for studying GHI prediction models based on ground-based cloud images and machine learning.

The decellularized extracellular matrix (dECM) is capable of promoting stem cell proliferation, migration, adhesion, and differentiation. It is a promising biomaterial for application and clinical translation in the field of periodontal tissue engineering as it most effectively preserves the complex array of ECM components as they are in native tissue, providing ideal cues for regeneration and repair of damaged periodontal tissue. dECMs of different origins have different advantages and characteristics in promoting the regeneration of periodontal tissue. dECM can be used directly or dissolved in liquid for better flowability. Multiple ways were developed to improve the mechanical strength of dECM, such as functionalized scaffolds with cells that harvest scaffold-supported dECM through decellularization or crosslinked soluble dECM that can form injectable hydrogels for periodontal tissue repair. dECM has found recent success in many periodontal regeneration and repair therapies. This review focuses on the repairing effect of dECM in periodontal tissue engineering, with variations in cell/tissue sources, and specifically discusses the future trend of periodontal regeneration and the future role of soluble dECM in entire periodontal tissue regeneration.

The cyclic nucleotide-gated ion channel (CNGC) family affects the uptake of Ca2+, regulates the growth and development, pathogen defense, and abiotic stress tolerance in plants. However, the systematic identification, origin, and function of the CNGC gene family has not been performed in Brassica napus. In the present study, we identified 61 putative BnaCNGC genes in the B. napus genome, which are non-randomly localized on 18 chromosomes, and could be classified into five major groups: Group I, II, III, IV-a, and IV-b. Gene structure, multiple sequence alignment, and MEME analysis showed that all the CNGC genes are intron rich and conserved. The expression analysis showed that the BnaCNGC genes have different expression patterns in B. napus, under different phytohormones, abiotic stresses (cold, hot, waterlogging), and infection of Sclerotinia sclerotiorum. Among them, four genes (BnaC03g31050D, BnaC03g31720D, BnaA05g01380D and BnaC04g01250D) from Group I and two genes (BnaCnng45430D and BnaA03g34680D) from Group IV-a, all were strongly induced by SA and infection of S. sclerotiorum, and reduced by cold and heat stresses, suggesting their importance in the abiotic and biotic stress responses in rapeseed. Our comprehensive genome-wide analysis represents a rich data resource for studying the CNGC gene family in B. napus.

Abstract Background TIFY is a plant-specific protein family with a diversity of functions in plant development and responses to stress and hormones, which contains JASMONATE ZIM-domain (JAZ), TIFY, PPD and ZML subfamilies. Despite extensive studies of TIFY family in many other species, TIFY has not yet been characterized in Brassica napus. Results In this study, we identified 77, 36 and 39 TIFY family genes in the genome of B. napus, B. rapa and B. oleracea, respectively. Results of the phylogenetic analysis indicated the 170 TIFY proteins from Arabidopsis, B. napus, B. rapa and B. oleracea could be divided into 11 groups: seven JAZ groups, one PPD group, one TIFY group, and two ZIM/ZML groups. The molecular evolutionary analysis showed that TIFY genes were conserved in Brassicaceae species. Gene expression profiling and qRT-PCR revealed that different groups of BnaTIFY members have distinct spatiotemporal expression patterns in normal conditions or following treatment with different abiotic/biotic stresses and hormones. The BnaJAZ subfamily genes were predominantly expressed in roots and up-regulated by NaCl, PEG, freezing, methyl jasmonate (MeJA), salicylic acid (SA) and Sclerotinia sclerotiorum in leaves, suggesting that they have a vital role in hormone signaling to regulate multiple stress tolerance in B. napus. Conclusions The extensive annotation and expression analysis of the BnaTIFY genes contributes to our understanding of the functions of these genes in multiple stress responses and phytohormone crosstalk in B. napus.

Catalytic reductive coupling of two electrophiles and one C = C bond is usually performed by two electron transfer metal catalysis. Herein, the authors show a visible light photoredox-catalyzed successive single electron transfer leading to dearomative arylcarboxylation of indoles with CO2 and generating indoline-3-carboxylic acids.

Objectives: This study aimed to describe cardiovascular risk and cardiovascular disease (CVD) knowledge among older adults, and further explore the association between knowledge and risk. Methods: In this cross-sectional study, we enrolled 1120 older adults who received physical examination in health centers. The participants were interviewed to obtain their behavioral risk factors related to CVD and clinical characteristics. A risk prediction chart was used to predict participants’ cardiovascular risk based on clinical characteristics and behavioral risk factors. Participants’ CVD knowledge was collected with a pretested knowledge questionnaire. Results: Among the 1120 participants, 240 (21.4%) had low cardiovascular risk, 353 (31.5%) had moderate cardiovascular risk, 527 (47%) had high and very high cardiovascular risk. The knowledge level about CVD among 0.8% of the 1120 participants was good while that of 56.9% was poor. Lower CVD knowledge level, older age, lower income, and lower educational level were the independent factors of higher cardiovascular risk level. Conclusions: This study highlights the need to reduce the cardiovascular risk among older adults. CVD knowledge should be considered when developing health interventions.

Seashore paspalum (Paspalum vaginatum) is an important warm-season turfgrass distributed in tropical and coastal areas. It has excellent resistance to abiotic stresses, such as salinity, drought, and low temperature. However, the research on genetic diversity of local P. vaginatum collections from China is limited. In this study, the genetic diversity among 58 P. vaginatum accessions from four different provinces in China and four cultivars were assessed using simple sequence repeat (SSR) markers. The results indicated that a total of 45 alleles were detected by 19 polymorphic markers, with a range of 2 to 4 and an average of 2.4 alleles per marker. The genetic similarity coefficients between each pair of the 58 P. vaginatum accessions and four cultivars ranged from 0.51 to 1.00, with an average of 0.77. The range of variation of Shannon diversity index of each SSR marker was 0.047 to 1.075, with an average of 0.486. The polymorphic information content of each SSR marker varies from 0.016 to 0.577, with an average of 0.249. The results of cluster analysis and principal component analysis (PCA) showed that 58 P. vaginatum accessions and four cultivars were divided into four groups. These results provide the theoretical basis for the genetic diversity assessments and molecular marker–assisted breeding of P. vaginatum species.

To examine the role of metabolites in wheat stamen and pistil development, metabolomic analyses of pistilloid stamens (PS), pistils (P), and stamens (S) from a novel wheat mutant homologous transformation sterility-1 (HTS-1) and controls from their sib-line CSTP were conducted using base gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Then, the metabolomic data were integrated with previously published transcriptomic data and analysed. In total, 141 annotated metabolites were determined from P, PS and S tissues by comparison with reference standards. A total of 90, 93 and 18 different metabolites were identified in S vs. PS, S vs. P and P vs. PS, respectively. Among the different metabolites, 80 may be associated with stamen and pistil growth. Using integration evaluations of both the previous transcriptome data and the 80 various metabolites, we found two perturbed pathways that significantly affect flower development in plants, namely, the phenylpropanoid biosynthesis and cysteine and methionine metabolism. The ethylene synthesis pathway, one key branch of the cysteine and methionine metabolic pathways, could have a pivotal role in pistillody growth involving HTS-1. We found two key enzyme genes in the ethylene synthesis pathway (the SAM synthase gene and the ACC synthase gene) that have higher expression levels in stamens than in pistilloid stamens or pistils. We speculate, that the decrease in ethylene content during stamen development leads to pistillody traits in HTS-1. This study helps elucidate the molecular mechanisms underlying stamen and pistil growth in wheat.

IntroductionSeveral teaching methods have been used in clinical nursing teaching to increase quality and efficiency, but disagreements over their effects persist. This study will evaluate the effects of five teaching methods in clinical nursing on nursing students' knowledge, skill scores, learning satisfaction, and patients' satisfaction.MethodsWe will conduct searches in PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure Database (CNKI), China Biological literature database (CBM), Wanfang Database, and China Science and Technology Journal Database (CSTJ) up to April 2022. Relevant randomized controlled trials meeting the eligibility criteria will be included. And the study selection and data extraction will be independently screened for eligibility by two authors. The quality of evidence will be evaluated using the Cochrane risk of bias tool. Pairwise meta-analysis and network meta-analysis (NMA) will be conducted using Rev Man, Stata, and R software. Statistical analyses including homogeneity tests, sensitivity analysis, transitivity tests, consistency tests, and publication bias will be completed.Ethics and disseminationNo formal research ethics approval is required. The results will be disseminated to a peer-reviewed journal for publication.Protocol registration numberINPLASY2021120040.