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The goal of unbiased learning to rank (ULTR) is to leverage implicit user feedback for optimizing learning-to-rank systems. Among existing solutions, automatic ULTR algorithms that jointly learn user bias models (i.e., propensity models) with unbiased rankers have received a lot of attention due to their superior performance and low deployment cost in practice. Despite their theoretical soundness, the effectiveness is usually justified under a weak logging policy, where the ranking model can barely rank documents according to their relevance to the query. However, when the logging policy is strong, e.g., an industry-deployed ranking policy, the reported effectiveness cannot be reproduced. In this paper, we first investigate ULTR from a causal perspective and uncover a negative result: existing ULTR algorithms fail to address the issue of propensity overestimation caused by the query-document relevance confounder. Then, we propose a new learning objective based on backdoor adjustment and highlight its differences from conventional propensity models, which reveal the prevalence of propensity overestimation. On top of that, we introduce a novel propensity model called Logging-Policy-aware Propensity (LPP) model and its distinctive two-step optimization strategy, which allows for the joint learning of LPP and ranking models within the automatic ULTR framework, and actualize the unconfounded propensity estimation for ULTR. Extensive experiments on two benchmarks demonstrate the effectiveness and generalizability of the proposed method., 11 pages, 5 figures

Cross view action recognition (CVAR) seeks to recognize a human action when observed from a previously unseen viewpoint. This is a challenging problem since the appearance of an action changes significantly with the viewpoint. Applications of CVAR include surveillance and monitoring of assisted living facilities where is not practical or feasible to collect large amounts of training data when adding a new camera. We present a simple yet efficient CVAR framework to learn invariant features from either RGB videos, 3D skeleton data, or both. The proposed approach outperforms the current state-of-the-art achieving similar levels of performance across input modalities: 99.4% (RGB) and 99.9% (3D skeletons), 99.4% (RGB) and 99.9% (3D Skeletons), 97.3% (RGB), and 99.2% (3D skeletons), and 84.4%(RGB) for the N-UCLA, NTU-RGB+D 60, NTU-RGB+D 120, and UWA3DII datasets, respectively.

Crops are constantly challenged by different environmental conditions. Seed treatment by nanomaterials is a cost-effective and environmentally-friendly solution for environmental stress mitigation in crop plants. Here, 56 seed nanopriming treatments are used to alleviate environmental stresses in maize. Seven selected nanopriming treatments significantly increase the stress resistance index (SRI) by 13.9% and 12.6% under salinity stress and combined heat-drought stress, respectively. Metabolomics data reveals that ZnO nanopriming treatment, with the highest SRI value, mainly regulates the pathways of amino acid metabolism, secondary metabolite synthesis, carbohydrate metabolism, and translation. Understanding the mechanism of seed nanopriming is still difficult due to the variety of nanomaterials and the complexity of interactions between nanomaterials and plants. Using the nanopriming data, we present an interpretable structure-activity relationship (ISAR) approach based on interpretable machine learning for predicting and understanding its stress mitigation effects. The post hoc and model-based interpretation approaches of machine learning are combined to provide complementary benefits and give researchers or policymakers more illuminating or trustworthy results. The concentration, size, and zeta potential of nanoparticles are identified as dominant factors for correlating root dry weight under salinity stress, and their effects and interactions are explained. Additionally, a web-based interactive tool is developed for offering prediction-level interpretation and gathering more details about specific nanopriming treatments. This work offers a promising framework for accelerating the agricultural applications of nanomaterials and may profoundly contribute to nanosafety assessment., 30 pages, 6 figures

Purpose: To study the mechanism by which adiponectin regulates the malignant biological behavior of endometrial cancer cells. Methods: RL95-2 cells were cultured and re-suspended in complete medium. A preliminary study showed that adiponectin (20 μg/mL) has the most inhibitory effect on cellular proliferation. The cells were divided into control group, 20 μg/mL adiponectin group, and 20 μg/mL adiponectin + 10 μmol/L AMPK inhibitor group, with 4 repeat wells set up for each group. Cell proliferation, apoptosis, invasion and migration ability, as well as the expression levels of MMP-9, Bcl-2, p-AMPK, p-mTOR and p-4ebp1 were determined using standard procedures. Results: Cell proliferation was significantly higher in the 20 μg/mL adiponectin group than in the 10 μg/mL adiponectin group (p < 0.05). Relative to the control group, apoptosis and p-AMPK expression level in the 10 μg/mL adiponectin group increased, while cell invasion and migratory potential, as well as expression levels of MMP-9, Bcl-2, p-mTOR and p-4ebp1 declined significantly (p < 0.05). The apoptosis and expression level of p-AMPK in the 20 μg/mL adiponectin + 10 μmol/L AMPK inhibitor group decreased, while cell invasion, migratory ability, and amounts of MMP-9, Bcl-2, p-mTOR and p- 4ebp1 were elevated, relative to the 20 μg/mL adiponectin group (p < 0.05). Conclusion: Adiponectin promotes apoptosis of endometrial cancer cells via AMPK/mTOR signaling pathway, and inhibits cell proliferation, invasion and migration. Thus, adiponectin has the potential to exert anti-tumor effect in humans.

Lipid metabolism is associated with lymphomagenesis and functions as a new therapeutic target in patients with lymphoma. Several serum lipids and lipoproteins have prognostic value in solid tumors; however, their value in diffuse large B-cell lymphoma (DLBCL) has been poorly described. We retrospectively analyzed and compared pre-treatment serum lipid and lipoprotein levels, including triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (ApoA-I), and apolipoprotein B (ApoB) between 105 DLBCL and 105 controls (no DLBCL). The prognostic significance of serum lipid and lipoprotein levels was determined using univariate and multivariate Cox proportional hazards models. The primary outcomes, overall survival (OS) and progression-free survival (PFS), were assessed by the Kaplan-Meier method. We combined the International Prognostic Index (IPI) with ApoA-I to build a nomogram model (IPI-A) to predict the OS and PFS of DLBCL. Serum TG, LDL-C, HDL-C, ApoA-I, and ApoB levels were significantly lower in the DLBCL patients than in controls and significantly increased after chemotherapy. Multivariate analyses showed that the ApoA-I level was an independent predictor of OS and PFS. In addition, our findings indicated that the prognostic index IPI-A significantly improves risk prediction over the traditional IPI score system. ApoA-I is an independent prognostic factor associated with poor OS and PFS in DLBCL patients. Our findings suggested that IPI-A is a prognostic index accurately used for risk assessment in patients with DLBCL.

OBJECTIVE: To evaluate the efficacy and safety of Shengmai Yin (生脉饮, SMY) on visual analogue scale (VAS) for cardiopulmonary symptoms in coronavirus disease 2019 (COVID-19) convalescent patients. METHODS: In this randomized, double blind and multicenter controlled trial, a total of 200 COVID-19 convalescent patients who with cardiopulmonary symptoms were enrolled from three medical centers in Hubei, China. These patients were randomized divided into trial group and the control group, 100 patients in each one, SMY and its placebo were applied to respectively, for two weeks. VAS of clinical symptoms included shortness of breath, hidrosis, chest distress, palpitation, and dry cough was performed at 0, 1, 2 weeks. Decrease in VAS of 30% or more was defined as effective, and a reduction in VAS of 0 was defined as curative. RESULTS: A total of 192 completed the study. The VAS of TCM symptoms showed there was no difference in baseline between the two groups. The VAS in both groups was down-regulated, and there was no significant difference in VAS and cure rates at the first and second week between the two groups. There was no significant difference in breath, hidrosis, palpitation, and dry cough between the two groups but SMY treatment for two weeks has remarkable therapeutic effects in chest distress than placebo. CONCLUSIONS: SMY could effectively ameliorate the symptoms of chest distress, and improve the quality of life of the COVID-19 convalescent patients.

Additional file 1: Supplementary Tables

Objective To establish a rapid phenotypic antibiotic susceptibility testing of Acinetobacter baumannii based on surfactant-propidium monoazide (PMAxx)-qPCR reaction system. Methods The type and optimal concentration of surfactant, exposure time and concentration of PMAxx were optimized successively. The copies of genomic DNA of Acinetobacter baumannii specific discriminant gene (blaOXA-51) was detected by qPCR. The susceptibility of Acinetobacter baumannii to antibiotics was determined by the antibiotic-bacterial co-reaction system. Results The Results indicated that 0.2% sodium lauroylsarcosinate and 20 μmol/L PMAxx after 5 min exposure effectively inhibited the DNA amplification of dead cells but had no effect on that of live cells. The phenotypic antibiotic susceptibility testing model based on this study could quickly (within 2 h) and accurately predict the susceptibility of Acinetobacter baumannii to doxycycline and levofloxacin (P < 0.01), and the reliable susceptibility of cefoperazone/sulbactam was predicted more than 2 h. Conclusion Our phenotypic antibiotic susceptibility test based on the sodium lauroylsarcosinate-PMAxx-qPCR system provides a basis for the treatment of Acinetobacter baumannii within a short time, and guides the clinical precision medication.

Brassica napus L. (B. napus) is a vital oilseed crop cultivated worldwide; low temperature (LT) is one of the major stress factors that limit its growth, development, distribution, and production. Even though processes have been developed to characterize LT-responsive genes, only limited studies have exploited the molecular response mechanisms in B. napus. Here the transcriptome data of an elite B. napus variety with LT adaptability was acquired and applied to investigate the gene expression profiles of B. napus in response to LT stress. The bioinformatics study revealed a total of 79,061 unigenes, of which 3,703 genes were differentially expressed genes (DEGs), with 2,129 upregulated and 1,574 downregulated. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis pinpointed that the DEGs were enriched in LT-stress-responsive biological functions and metabolic pathways, which included sugar metabolism, antioxidant defense system, plant hormone signal transduction, and photosynthesis. Moreover, a group of LT-stress-responsive transcription factors with divergent expression patterns under LT was summarized. A combined protein interaction suggested that a complex interconnected regulatory network existed in all detected pathways. RNA-seq data was verified using real-time quantitative polymerase chain reaction analysis. Based on these findings, we presented a hypothesis model illustrating valuable information for understanding the LT response mechanisms in B. napus.

Nanocarrier technology has been effectively applied to the development of drug delivery systems to overcome the limitations of traditional preparation. Its application has been extended to various pharmaceutical fields from injection preparation to oral preparation and external preparation, and now it has appeared in the field of cosmetics for beauty applications. The widespread influence of nanocarrier in the cosmetics industry is due to the fact that nanocarrier can effectively promote the percutaneous penetration and significantly increase skin retention of active components in functional cosmetics. Meanwhile, nanocarrier can effectively improve the water dispersion of insoluble active cosmetic ingredients, enhance the stability of efficacy components and achieve the codelivery of diverse cosmetics active ingredients. In this review, we summarized the current progress of nanocarrier technology in the functional cosmetics, including the types and the routes of dermal/transdermal drug delivery nanocarriers used in the functional cosmetics, the mechanism of nanocarriers promoting the percutaneous penetration of active cosmetic ingredients, the application and efficacy evaluation of different active cosmetic ingredients in nanocarriers and discussing the potential risks to human. This will provide a useful reference for the further development of nanocarriers in the field of functional cosmetics.

Purpose: To predict molecular targets and the mechanism of action of hyaluronic acid against various disease conditions. Methods: The present study was designed and conducted based on the principle of network pharmacology, protein-protein interaction (PPI) database, and biological process analysis. At a high confidence score, a protein network comprising seventeen human protein targets was achieved from STITCH (Search Tool for Interaction of Chemicals). Results: Cytoscape-based protein-protein interaction network (PPIN) with 342 nodes was developed and analyzed to ascertain the molecular basis of hyaluronic acid actions. It revealed that hyaluronic acid was mainly involved in various physiological processes including extracellular matrix (ECM) disassembly, collagen catabolic process, mucopolysaccharide metabolic process, and circadian regulation of gene expression. Conclusion: The retrieved pathways are known to be involved in causing several pathologies such as leukemia, psoriasis, tick-borne encephalitis, etc. These pathways are influenced by hyaluronic acid. However, further explanations are required to elucidate whether these targets of hyaluronic acid have a therapeutic or toxicological role.

Evidence suggests a potential relationship between gestational weight gain (GWG) and adverse birth outcomes. However, the role of maternal genetic polymorphisms remains unclear. This study was conducted to investigate whether the relationship of GWG with risk of adverse birth outcomes was modified by methylenetetrahydrofolate reductase (MTHFR) polymorphisms. A total of 2,967 Chinese pregnant women were included and divided into insufficient, sufficient, and excessive groups based on the Institute of Medicine (IOM) criteria. Polymorphisms of C677T and A1298C in gene MTHFR were genotyped. Multivariable logistic regression models were introduced after controlling major confounders. Excessive GWG was found to increase the odds ratio (OR) for macrosomia [OR = 3.47, 95% confidence interval (CI): 1.86–6.48] and large-for-gestational age (LGA, OR = 3.25, 95% CI: 2.23–4.74), and decreased the OR for small-for-gestational age (SGA, OR = 0.60, 95% CI: 0.45–0.79). Pregnant women with insufficient GWG had a higher frequency of SGA (OR = 1.68, 95% CI: 1.32–2.13) and a lower rate of LGA (OR = 0.51, 95% CI: 0.27–0.96). Interestingly, significant associations of GWG categories in relation to low birth weight (LBW), macrosomia, and SGA were only suggested among pregnant women with MTHFR A1298C AA genotype. Among pregnant women with insufficient GWG group, an increased risk of 3.96 (95% CI: 1.57–10.01) for LBW was observed among subjects with the A1298C AA genotype, compared to the AC+CC genotype group. GWG categories are closely related to LBW, macrosomia, SGA and LGA, and the associations were modified by the polymorphism of MTHFR A1298C.

To compare the effect of micro-needle knife therapy and betahistine mesilate tablets in the treatment of cervical vertigo (CV) and the influence on the mean blood flow velocity (Vm) of vertebral artery.A total of 200 patients with CV were randomly divided into a micro-needle knife group (100 cases, 5 cases dropped off) and a medication group (100 cases, 3 cases dropped off). In the micro-needle knife group, micro-needle knife was performed on the suboccipital triangle of the atlantoaxial segment of the posterior neck, once every other day, for a total of 7-time treatment. The medication group received oral betahistine mesilate tablets, 6 mg each time, three times a day, for 14 consecutive days. The dizziness handicap inventory (DHI) scores of the two groups were observed before treatment, after treatment and during follow-up 3 months after treatment; the Vm of vertebral artery was compared between the two groups before and after treatment, and the clinical effect was evaluated during follow-up.After treatment and during follow-up, the DHI scores of the two groups were lower than those before treatment (Micro-needle knife therapy can improve vertigo symptoms and balance dysfunction, increase the mean blood flow velocity of vertebral artery in CV patients, and its clinical efficacy is better than oral betahistine mesilate tablets.

Extracting regularities from ongoing stimulus streams to form predictions is crucial for adaptive behavior. Such regularities exist in terms of the content of the stimuli (i.e., “what” it is) and their timing (i.e., “when” it will occur), both of which are known to interactively modulate sensory processing. In real-world stimulus streams, regularities also occur contextually - e.g. predictions of individual notes vs. melodic contour in music. However, it is unknown whether the brain integrates predictions in a contextually congruent manner (e.g., if slower “when” predictions selectively interact with complex “what” predictions), and whether integrating predictions of simple vs. complex features rely on dissociable neural correlates. To address these questions, our study employed “what” and “when” violations at different levels - single tones (elements) vs. tone pairs (chunks) - within the same stimulus stream, while neural activity was recorded using electroencephalogram (EEG) in participants (N=20) performing a repetition detection task. Our results reveal that “what” and “when” predictions interactively modulated stimulus-evoked response amplitude in a contextually congruent manner, but that these modulations were shared between contexts in terms of the spatiotemporal distribution of EEG signals. Effective connectivity analysis using dynamic causal modeling showed that the integration of “what” and “when” prediction selectively increased connectivity at relatively late cortical processing stages, between the superior temporal gyrus and the fronto-parietal network. Taken together, these results suggest that the brain integrates different predictions with a high degree of contextual specificity, but in a shared and distributed cortical network.Significance statementPredictions of stimulus features, present in different statistically-regular contexts in the environment, are crucial to forming adaptive behavior. However, it is unknown if the brain integrates predictions selectively according to such contextual differences. By recording human electroencephalography during experimental manipulations of time-based and content-based predictions, we found that those predictions interactively modulated neural activity in a contextually congruent manner, such that local (vs. global) time-based predictions modulated content-based predictions of sequence elements (vs. chunks). These modulations were shared between contextual levels in terms of the spatiotemporal distribution of neural activity. This suggests that the brain integrates different predictions with a high degree of contextual specificity, but in a shared and distributed cortical network.

C63H57Cl2N13Ni3O6, monoclinic, P21/c$P{2}_{1}/c$, a = 16.136(4) Å, b = 16.432(4) Å, c = 23.881(6) Å, β = 101.900(3)°, V = 6196(3) Å3, Z = 4, Rgt(F) = 0.0461, wRref(F2) = 0.1357, T = 298 K [1], [2], [3].

Chili anthracnose is one of the most common and destructive fungal pathogens that affects the yield and quality of pepper. Although WRKY proteins play crucial roles in pepper resistance to a variety of pathogens, the mechanism of their resistance to anthracnose is still unknown. In this study, we found that CaWRKY50 expression was obviously induced by Colletotrichum scovillei infection and salicylic acid (SA) treatments. CaWRKY50-silencing enhanced pepper resistance to C. scovillei, while transient overexpression of CaWRKY50 in pepper increased susceptibility to C. scovillei. We further found that overexpression of CaWRKY50 in tomatoes significantly decreased resistance to C. scovillei by SA and reactive oxygen species (ROS) signaling pathways. Moreover, CaWRKY50 suppressed the expression of two SA-related genes, CaEDS1 (enhanced disease susceptibility 1) and CaSAMT1 (salicylate carboxymethyltransferase 1), by directly binding to the W-box motif in their promoters. Additionally, we demonstrated that CaWRKY50 interacts with CaWRKY42 and CaMIEL1 in the nucleus. Thus, our findings revealed that CaWRKY50 plays a negative role in pepper resistance to C. scovillei through the SA-mediated signaling pathway and the antioxidant defense system. These results provide a theoretical foundation for molecular breeding of pepper varieties resistant to anthracnose.

The aim of this assessment was to determine the information needs, resources, and resource preferences and self/family-management challenges of parents caring for a child with asthma in China. The acceptance of asthma and consolidated framework for implementation research guided the study. A cross-sectional, descriptive design was used. Seventy-one parents of a child receiving care in an outpatient respiratory clinic completed a three-part, pragmatic, self-report survey. Quantitative data were analyzed using descriptive statistics and qualitative data using thematic analysis. Parents, who needed more knowledge about asthma, sought information from internet sources. However, most parents preferred receiving information during in-person consultation with trained specialists. Management challenges revolved around understanding asthma information, formulating beliefs about asthma, experiencing distressing thoughts and feelings, forming supportive networks, and meeting their child’s emotional needs. Evidence supports expanding nursing roles in China to include extended time for initial in-person parental interactions and follow-up using reliable clinic-based internet counseling.

Background Querying drug-induced gene expression profiles with machine learning method is an effective way for revealing drug mechanism of actions (MOAs), which is strongly supported by the growth of large scale and high-throughput gene expression databases. However, due to the lack of code-free and user friendly applications, it is not easy for biologists and pharmacologists to model MOAs with state-of-art deep learning approach. Results In this work, a newly developed online collaborative tool, Genetic profile-activity relationship (GPAR) was built to help modeling and predicting MOAs easily via deep learning. The users can use GPAR to customize their training sets to train self-defined MOA prediction models, to evaluate the model performances and to make further predictions automatically. Cross-validation tests show GPAR outperforms Gene set enrichment analysis in predicting MOAs. Conclusion GPAR can serve as a better approach in MOAs prediction, which may facilitate researchers to generate more reliable MOA hypothesis.

Oroxin A (OA) is a flavonoid isolated from Oroxylum indicum (L.) Kurz that has various biological activities, including antioxidant activities. This study aimed to examine the viability of using OA in an in vitro culture (IVC) medium for its antioxidant effects and related molecular mechanisms on porcine blastocyst development. In this study, we investigated the effects of OA on early porcine embryo development via terminal deoxynucleotidyl transferase dUTP nick-end labeling, 5-ethynyl-2'-deoxyuridine labeling, quantitative reverse transcription PCR, and immunocytochemistry. Embryos cultured in the IVC medium supplemented with 2.5 μM of OA had an increased blastocyst formation rate, total cell number, and proliferation capacity, along with a low apoptosis rate. OA supplementation decreased reactive oxygen species levels while increasing glutathione levels. OA-treated embryos exhibited an improved intracellular mitochondrial membrane potential and reduced autophagy. Moreover, levels of pluripotency- and antioxidant-related genes were upregulated, whereas those of apoptosis- and autophagy-related genes were downregulated by OA addition. In conclusion, OA improves preimplantation embryonic development by reducing oxidative stress and enhancing mitochondrial function.

Guo-feng Xie,1,* Luo-dan Zhao,2,3,* Qiang Chen,4,* Dong-xiao Tang,4 Qiong-yu Chen,4 Hong-fei Lu,4 Jia-rong Cai,5 Zheng Chen4 1Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong Province 510095, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangzhou Higher Education Institutes, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, People’s Republic of China; 5Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia-rong CaiDepartment of Urology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong Province, People’s Republic of ChinaTel +86-20-82179727Fax +86-20-85253336Email caijiar@mail.sysu.edu.cnZheng ChenDepartment of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong Province, People’s Republic of ChinaFax +86-20-85253336Email chenzh68@mail.sysu.edu.cnPurpose: Oral squamous cell carcinoma (OSCC) is a common malignancy of the oral cavity. As the survival rate of OSCC patients is low, it is crucial to explore new markers and therapeutic targets for early diagnosis of the disease. A high level of actinin alpha 1 (ACTN1) in patients could serve as an independent prognostic factor of acute myeloid leukemia. However, the role of ACTN1 in OSCC remains unclear. In the present study, we aimed to investigate the role of ACTN1 in OSCC.Methods: ACTN1 protein levels in tissues were determined by immunohistochemical (IHC) staining. The correlation of ACTN1 expression with clinicopathological features and prognosis was analyzed. Univariate and multivariate analyses were performed. The effect of ACTN1 knockdown on cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition (EMT), and the cell cycle was evaluated using Western blotting, Cell Counting Kit‑8 (CCK8) assays, flow cytometry analysis, transwell assays, wound-healing assays, and nude mouse models of subcutaneous xenograft and pulmonary metastasis.Results: Based on the total score of ACTN1 IHC staining analysis, ACTN1 expression was found to be low in 10 normal mucosal tissues, 48 normal mucosal tissues adjacent to OSCC, and 19 OSCC tissues, but high in 29 OSCC tissues. ACTN1 protein levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 expression was an independent predictor of poor prognosis of OSCC. Using in vitro assays, we found that ACTN1 knockdown could induce cell cycle arrest, promote apoptosis, and inhibit EMT and cell proliferation, migration, and invasion in the OSCC cell lines, SCC-15 and HSC-3. Moreover, ACTN1 knockdown inhibited subcutaneous tumor growth and pulmonary metastasis in vivo.Conclusion: ACTN1 levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 knockdown could suppress cell proliferation and metastasis of OSCC. Our results suggested that ACTN1 may serve as a diagnostic and prognostic marker of OSCC.Keywords: actinin alpha 1, poor prognosis, oral squamous cell carcinoma, knockdown, proliferation, metastasis

Background Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are aberrantly expressed in various cancers. However, the functional roles of lncRNAs in breast cancer remain largely unknown. Methods Based on public databases and integrating bioinformatics analyses, the overexpression of lncRNA BCRT1 in breast cancer tissues was detected and further validated in a cohort of breast cancer tissues. The effects of lncRNA BCRT1 on proliferation, migration, invasion and macrophage polarization were determined by in vitro and in vivo experiments. Luciferase reporter assay and RNA immunoprecipitation (RIP) were carried out to reveal the interaction between lncRNA BCRT1, miR-1303, and PTBP3. Chromatin immunoprecipitation (ChIP) and RT-PCR were used to evaluate the regulatory effect of hypoxia-inducible factor-1α (HIF-1α) on lncRNA BCRT1. Results LncRNA BCRT1 was significantly upregulated in breast cancer tissues, which was correlated with poor prognosis in breast cancer patients. LncRNA BCRT1 knockdown remarkably suppressed tumor growth and metastasis in vitro and in vivo. Mechanistically, lncRNA BCRT1 could competitively bind with miR-1303 to prevent the degradation of its target gene PTBP3, which acts as a tumor-promoter in breast cancer. LncRNA BCRT1 overexpression could promote M2 polarization of macrophages, mediated by exosomes, which further accelerated breast cancer progression. Furthermore, lncRNA BCRT1 was upregulated in response to hypoxia, which was attributed to the binding of HIF-1α to HREs in the lncRNA BCRT1 promoter. Conclusions Collectively, these results reveal a novel HIF-1α/lncRNA BCRT1/miR-1303/PTBP3 pathway for breast cancer progression and suggest that lncRNA BCRT1 might be a potential biomarker and therapeutic target for breast cancer.

Purpose Oral squamous cell carcinoma (OSCC) is a common malignancy of the oral cavity. As the survival rate of OSCC patients is low, it is crucial to explore new markers and therapeutic targets for early diagnosis of the disease. A high level of actinin alpha 1 (ACTN1) in patients could serve as an independent prognostic factor of acute myeloid leukemia. However, the role of ACTN1 in OSCC remains unclear. In the present study, we aimed to investigate the role of ACTN1 in OSCC. Methods ACTN1 protein levels in tissues were determined by immunohistochemical (IHC) staining. The correlation of ACTN1 expression with clinicopathological features and prognosis was analyzed. Univariate and multivariate analyses were performed. The effect of ACTN1 knockdown on cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition (EMT), and the cell cycle was evaluated using Western blotting, Cell Counting Kit‑8 (CCK8) assays, flow cytometry analysis, transwell assays, wound -healing assays, and nude mouse models of subcutaneous xenograft and pulmonary metastasis. Results Based on the total score of ACTN1 IHC staining analysis, ACTN1 expression was found to be low in 10 normal mucosal tissues, 48 normal mucosal tissues adjacent to OSCC, and 19 OSCC tissues, but high in 29 OSCC tissues. ACTN1 protein levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 expression was an independent predictor of poor prognosis of OSCC. Using in vitro assays, we found that ACTN1 knockdown could induce cell cycle arrest, promote apoptosis, and inhibit EMT and cell proliferation, migration, and invasion in the OSCC cell lines, SCC-15 and HSC-3. Moreover, ACTN1 knockdown inhibited subcutaneous tumor growth and pulmonary metastasis in vivo. Conclusion ACTN1 levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 knockdown could suppress cell proliferation and metastasis of OSCC. Our results suggested that ACTN1 may serve as a diagnostic and prognostic marker of OSCC.

High-intensity interval training (HIIT) is a time-efficient alternative to moderate-intensity continuous training (MICT) to improve metabolic health in older individuals. However, differences in adipose tissue metabolism between these two approaches are unclear. Here, we evaluated the effects of HIIT and MICT on metabolic phenotypes in aged rats. HIIT significantly decreased fat mass, increased percent lean mass, decreased fat-to-lean ratio, reduced serum high-sensitivity C-reactive protein, increased serum interleukin-10 levels, and decreased perirenal adipose tissue leptin compared with rats in the sedentary (SED) group. HIIT also increased pregnenolone, cortisol, and corticosterone in both adipose tissue and serum. Both exercise modalities enhanced hormone-sensitive lipase and adipose triglyceride lipase expression compared with the SED group and decreased palmitic acid, stearic acid, octadecadienoic acid, urea, 1-heptadecanol, and α-tocopherol. MICT was related to glycerolipid metabolism, whereas HIIT was related to steroid hormone biosynthesis. Overall, HIIT showed more favorable regulation of anti-inflammatory activity than MICT.

Osteosarcoma is the most common skeletal malignancy and is the second leading cause of cancer death in adolescents. Its highly aggressive nature and high propensity to metastasize lead to an extremely poor prognosis for patients with osteosarcoma. Therefore, finding a suitable treatment has become a matter of urgency. In this study, we first divided the samples into metastatic and non-metastatic groups using the Target database and obtained 1136 differentially expressed genes (DEGs) using differential analysis. A PPI network was constructed to analyze the network of action relationships among DEGs, and the top 10 genes were derived using the MCC algorithm in Cytoscape software. A risk scoring system for 10 key genes was constructed using the LASSO-COX prognostic risk model, and genes associated with osteosarcoma prognosis were screened based on multifactorial COX. COL5A2 gene was highly expressed in metastatic osteosarcoma and led to a poor prognosis. Furthermore, qRT-PCR and immunofluorescence assays confirmed the high expression of COL5A2 in human osteosarcoma cells. CCK-8 assay and scratch WB was used to determine whether the downregulation of COL5A2 expression inhibits the TGF-β signaling and Wnt/β-Catenin signaling pathways. In this study, we screened COL5A2 for prognostic relevance to osteosarcoma through bioinformatics analysis and demonstrated that COL5A2 inhibited osteosarcoma invasion and metastasis by suppressing the TGF-β signaling and Wnt/β-Catenin signaling pathways.

To observe the clinical efficacy of micro needle knife therapy on cervical vertigo.A total of 300 patients with cervical vertigo treated from January 1, 2017 to December 31, 2019 were randomly divided into micro needle knife group (96 cases, 4 cases falling off), traditional acupuncture group (96 cases, 4 cases falling off) and oral drug group(95 cases, 5 cases falling off). The micro needle knife group was treated with micro needle knife in the local upper cervical segment once every other day for 7 times; the traditional acupuncture group was treated with traditional acupuncture once a day for 2 weeks;the oral drug group was given Merislon (betahistine mesilate tablets) orally, 6 mg each time, 3 times a day for 2 weeks. The patients were followed up before treatment, at the end of treatment and 3 months after treatment. The dizziness handicap inventory(DHI) was observed and the curative effect was evaluated according to the DHI score.At the end of the course of treatment and 3 months after the treatment, DHI scores of the three groups were significantly lower than those before treatment(Micro needle knife loosening atlantoaxial soft tissue has obvious curative effect on cervical vertigo which clinical cure rate, effective rate and treatment time required for cured patients are better than traditional acupuncture and oral drug.

Many deep neural networks are susceptible to minute perturbations of images that have been carefully crafted to cause misclassification. Ideally, a robust classifier would be immune to small variations in input images, and a number of defensive approaches have been created as a result. One method would be to discern a latent representation which could ignore small changes to the input. However, typical autoencoders easily mingle inter-class latent representations when there are strong similarities between classes, making it harder for a decoder to accurately project the image back to the original high-dimensional space. We propose a novel framework, Memory Defense, an augmented classifier with a memory-masking autoencoder to counter this challenge. By masking other classes, the autoencoder learns class-specific independent latent representations. We test the model's robustness against four widely used attacks. Experiments on the Fashion-MNIST & CIFAR-10 datasets demonstrate the superiority of our model. We make available our source code at GitHub repository: https://github.com/eashanadhikarla/MemDefense, 11 pages

Supplemental material, sj-docx-4-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-3-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-1-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-2-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-7-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-4-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

The ability of fiber to collect optical signals after polymerization and MMF etching technique are shown in the Figure S1

Supporting information

Supplemental material, sj-docx-3-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-6-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Additional file 1: Figure S1. ISGs are induced by ZIKV infection in A549 cells. a-c qRT-PCR analysis of MX1, IDO1 and RSAD2 mRNA in A549 cells stimulated with increasing dose of ZIKV (FSS13025) infection. Figure S2. TRIM22 inhibits ZIKV infection in vitro. a Vero cells in 24-well plate were transfected with increasing amount of pM01-TRIM22 plasmid, 12 h later, the cells were infected with ZIKV GZ01 at MOI = 0.01, IFA of ZIKV E protein was conducted at 24 hpi. Scale bar, 100 μm. b Western blot analysis of lysates from A549 cells and TRIM22−/− A549 cells. c-d SH-SY5Y cells were transfected with pM01-TRIM22 plasmid, 12 h later, the cells were infected with ZIKV GZ01 at MOI = 0.1, ZIKV loads in cell lysates were measured by qRT-PCR at 24 hpi (c) and 48 hpi (d). e Western blot analysis of lysates from SH-SY5Y cells which were transfected with either NC siRNA or TRIM22 siRNAs. f SH-SY5Y cells were transfected with NC siRNA or TIRM22 siRNAs, 24 h later, the cells were infected with ZIKV GZ01 at MOI = 0.01, ZIKV loads in cell lysates were measured by qRT-PCR at 48 hpi. Figure S3. Model of BiLC system and IFA used to test the interactions between TRIM22 and ZIKV proteins. a Work model of GlucN-TRIM22 and GlucC-ZIKV NS1 or NS3 in BiLC system. b IFA of A549 cells that were co-transfected with pHA-TRIM22 and pHis-NS1 or pHis-NS3 plasmids, stained with HA and His tag antibody, then imaged by fluorescence microscope. Scale bar, 10 μm. Figure S4. TRIM22 mediates the K48 ubiquitylation of ZIKV NS1 and NS3 proteins. Western blot analysis of total cell lysates or immunoprecipitated proteins from HEK293T cells co-transfected with pM01-TRIM22, pHis-NS1 or pHis-NS3 and pHA-K48 (a) or pHA-K63(b) plasmids and treated with MG132, as indicated. Figure S5. TRIM22 inhibits YFV infection in vitro. a TRIM22 was over expressed in A549 cells, the cells were subsequently infected with YFV at MOI = 0.01, 12 h post transfection, YFV load in culture supernatant was measured by qRT-PCR. b TRIM22−/−A549 cells were infected with YFV, the cell lysates were measured by qRT-PCR. qRT-PCR data are means ± SEM from three independent experiments. **P < 0.05, **P < 0.01 and ***P < 0.001 by Student’s t test. Table S1. The list of ISG, ZIKV, DENV and YFV primers used in this study.

Additional file 1. Supplementary Materials and Methods, Supplementary Tables, and Supplementary Figures.

Supplemental material, sj-docx-6-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-7-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-5-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Supplemental material, sj-docx-5-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

Background Resilience is a concept that is increasingly used by nurses and other health professionals when discussing management of psychosocial distress for people living with cancer. Empirical studies suggest that low levels of resilience may contribute to high levels of psychological distress in people affected by cancer. Despite often being proffered as a solution, the conceptualisation of resilience for adult cancer patients has not been addressed so far. Aim The overarching aim of this two-phase study was to clarify the meaning of individual resilience in the context of adult cancer care. Specifically, this study aimed to: 1. Conceptualise individual resilience in adult cancer care and developing a preliminary conceptual model of individual resilience; 2. Examine and refine the preliminary conceptual model of individual resilience based on the perspectives and experience of resilience in the population of adults with a certain cancer (i.e. colorectal cancer) in the context of their illness. Methods For the first phase of the study, the concept analysis method recommended by Walker and Avant was employed to conceptualise individual resilience in adult cancer care. Based on the conceptualisation of individual resilience, we developed a preliminary conceptual model of individual resilience in adult cancer care. For the second phase of the study, qualitative inquiry was applied to guide the study. Twelve participants diagnosed with colorectal cancer that had completed treatment were recruited from a tertiary hospital in Australia. The meaning of resilience was explored using in-depth individual interviews. Following thematic analysis, the elements of the preliminary model of individual resilience were mapped against the themes and subthemes to refine the preliminary conceptual model. Results Based on our concept analysis, individual resilience in adult cancer care was defined as “the capacity and dynamic recalibration process of an individual to change their psychological distress level and individual functioning performance through their interaction with the environment when facing cancer-related adversity”. Our refined conceptual model of individual resilience in adults with colorectal cancer comprised five components (themes). When faced with adversity related to diagnosis and treatment for colorectal cancer, participants initially strove to seek motivations to move forward, through identifying and clarifying important things to live for, drawing on mental efforts and strength, and accessing the spiritual self. With the motivation to move forward, participants strove to live as normally as they could during their cancer journey. Meanwhile, they also made efforts to adapt and manage themselves as well as draw on external supports to respond to various illness-related adversities, which was also beneficial for them to achieve the goal of living a normal life. Once the adversity was overcome, individuals were able to reconsider their perception of self by reflecting on the changes they had made in their ability to manage adversity, and to set their values and life priorities. Conclusion This study expanded the body of knowledge on resilience in adult cancer care through clarifying the concept of resilience, developing and refining the conceptual model of resilience based on the perspectives and experience of resilience in adults with colorectal cancer in the context of their illness. This study bridged the gap in the lack of a consistent definition in existing resilience studies in adult cancer care. The concept clarification may contribute to a better understanding of the nature of resilience in people living with cancer for nurses and other health professionals. Understanding the nature of dynamic changes of resilience may be beneficial for improving health professionals’ awareness of regularly assessing psychosocial conditions of people affected by cancer, thereby facilitating early identification and referral to psychosocial support services for patients who may be at risk of developing adaptation difficulties. The refined conceptual model of resilience in adults with colorectal cancer could be used to guide the development of cancer-specific resilience measures as well as interventions that aim to facilitate resilience in individuals living with colorectal cancer.

Additional file 1: Supplemental Table 1. Cronbach’s alpha for the simplified Chinese DES for six simulation cases.

Supplemental material, sj-docx-2-his-10.1177_11786329221134352 for Gaps in the Utilization of Community Health Services for the Elderly Population in Rural Areas of Mainland China: A Systematic Review Based on Cross-Sectional Investigations by Shanshan Deng, Chenchen Zhang, Xing Guo, Hekai Lv, Yanyan Fan, Zhuoxin Wang, Dan Luo, Xiaoxia Duan, Xinying Sun and Fuzhi Wang in Health Services Insights

The ability of various bacteria to make use of solid substrates through extracellular electron transfer (EET) or extracellular electron uptake (EEU) has enabled the development of valuable biotechnologies such as microbial fuel cells (MFCs) and microbial electrosynthesis (MES). It is common practice to use metallic and semiconductive nanoparticles (NPs) for microbial current enhancement. However, the effect of NPs is highly variable between systems, and there is no clear guideline for effectively increasing the current generation. In the present review, the proposed mechanisms for enhancing current production in MFCs and MES are summarized, and the critical factors for NPs to enhance microbial current generation are discussed. Implications for microbially induced iron corrosion, where iron sulfide NPs are proposed to enhance the rate of EEU, photochemically driven MES, and several future research directions to further enhance microbial current generation, are also discussed.