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Background: Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent subtype of pancreatic cancer and one of the most malignant tumors worldwide. Due to the heterogeneity of its genomics and proteomics, the prognosis of PDAC remains disappointing despite advances in surgery and medicines. Recently, a novel form of programmed cell death, cuproptosis, was proposed, although its role in PDAC has not been investigated. This study aimed to quantify the expression of cuproptosis-related genes and characterize the novel subtypes of PDAC. Methods: To evaluate the pattern of cuproptosis in PDAC, the gene expression data and clinical information of 372 samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus cluster analysis was performed using the transcriptional levels, genetic alterations, and individual prognostic values of seven pre-selected cuproptosis-related genes (DLAT, LIPT1, FDX1, DLD, PDHB, PDHA1, and LIAS) to identify the novel subtypes associated with cuproptosis in PDAC. A univariate Cox regression analysis was used to determine the significant prognostic indicators and cuproptosis scores among the differentially expressed genes (DEGs) between the dividing subclusters, followed by a principal component analysis. The prognostic values, immune profiles, treatment sensitivities, and cuproptosis scores were evaluated between the different subgroups. Results: Seven cuproptosis-related genes showed aberrant expression levels and genetic alterations in the PDAC tumor microenvironment. Among them, LIPT1, LIAS, DLAT, PDHA1, and DLD were significantly correlated with overall survival. Based on the expression profiles of the seven cuproptosis-related genes, three cuproptosis clusters (Clusters A, B, and C) were identified, which were represented by different clinicopathologic features, gene expression levels, and biological processes. A total of 686 DEGs were identified among the three cuproptosis clusters, of which 35 prognosis-related DEGs were selected to further classify the PDAC samples into two subgroups with different survival rates, clinicopathologic features, immune infiltration levels, and drug sensitivities. Higher cuproptosis scores were associated with a significantly poorer prognosis. Conclusion: The cuproptosis subtypes, scores, and relevant genes represent valuable information for assessing the heterogeneity, treatment, and prognosis of PDAC. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of estrogen signaling in pancreatic adenocarcinoma (PAAD) was unclear. Here we investigated the expression patterns of three estrogen receptors (ERα, ERβ, and GPER) in 174 PAAD samples via immunohistochemistry staining. Positive expression of all three estrogen receptors was significantly correlated with better clinicopathological characteristics and prognosis, as well as more tertiary lymphoid structure (TLS) presence in PAAD. Upregulated expression of ERα and ERβ in PAAD was also significantly associated with increased CD8+ T-cell infiltration in vitro. In-silico analyses also revealed that the expression of estrogen receptors affects multiple pathways relevant to T-cell and B-cell behaviors. In summary, estrogen receptors may remodel the immune microenvironment and regulate the development of TLS in PAAD. The role of estrogen signaling in antitumor immunology remains unknown for non-traditional sex-biased cancer types such as pancreatic adenocarcinoma (PAAD). Tertiary lymphoid structures (TLS) are active zones composed of multiple types of immune cells, whose presence indicates anti-tumor immune responses. In this study, we employed a 12-chemokine signature to characterize potential gene categories associated with TLS development and identified seventeen major gene categories including estrogen receptors (ERs). Immunohistochemistry staining revealed the expression patterns of three ERs (ERα, ERβ, and GPER) in 174 PAAD samples, and their correlation with clinicopathological characteristics, immune cell infiltration levels, and intratumoral TLS presence was analyzed. The results indicated that ERα (+) and ERβ (+) were correlated with high tumor grade, and ERβ (+) and GPER (+) were correlated with lower TNM stage, and both ERα (+) and GPER (+) displayed a beneficial effect on prognosis in this cohort. Interestingly, positive staining of all three ERs was significantly correlated with the presence of intratumoral TLSs and infiltration of more active immune cells into the microenvironment. Moreover, the chemotaxis of CD8+T-cells to PAAD cells was significantly increased in vitro with upregulated expression of ERα or ERβ on PAAD cells. To conclude, our study showed a novel correlation between ER expression and TLS development, suggesting that ERs may play a protective role by enhancing anti-tumor immune responses in PAAD. [ABSTRACT FROM AUTHOR]

Purpose: MicroRNA (miRNA) is a class of short non-coding RNA molecules that functions in RNA silencing and post-transcriptional regulation of gene expression. This study aims to identify critical miRNA-mRNA regulation pairs contributing to bladder cancer (BLCA) pathogenesis. Patients and methods: MiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. The tool of GEO2R and R packages were used to screen differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) and DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The miRNA-mRNA regulation pair were screened from the experimentally validated miRNA-target interactions databases (miRTarbase and TarBase). Twenty-eight pairs of BLCA tissues were used to further verify the screened DE-miRNAs and DE-mRNAs by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). The correlation analysis between the selected miRNA-mRNAs regulation pair and clinical, survival and tumor-related phenotypes was performed in this study. Results: After miRTarBase, the analysis of 2 miRNA datasets, 6 mRNA datasets, and TCGA-BLCA dataset, a total of 13 miRNAs (5 downregulated and 8 upregulated in BLCA tissues) and 181 mRNAs (72 upregulated and 109 downregulated in BLCA tissues) were screened out. The pairs of miR-17-5p (upregulated in BLCA tissues) and TGFBR2 (downregulated in BLCA tissues) were verified in the external validation cohort (28 BLCA vs. 28 NC) using qRT-PCR. Areas under the ROC curve of the miRNA-mRNA regulation pair panel were 0.929 (95% CI: 0.885–0.972, p < 0.0001) in TCGA-BLCA and 0.767 (95% CI: 0.643–0.891, p = 0.001) in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing BLCA from normal controls. Correlation analysis showed that miR-17-5p and TGFBR2 correlated with tumor immunity. Conclusions: The research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of BLCA. [ABSTRACT FROM AUTHOR]

Background: The novel coronavirus disease 2019 (COVID-19) confirmed cases overseas have continued to rise in the last months, and many people overseas have chosen to return to China. This increases the risk of a large number of imported cases which may cause a relapse of the COVID-19 outbreak. In order to prevent imported infection, the Shenzhen government has implemented a closed-loop management strategy using nucleic acid testing (NAT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and requiring 14 days of medical observation for individuals with an overseas tour history (Hong Kong, Macao, Taiwan province and other countries). Our study aims to describe the status of COVID-19 infection among people entering Shenzhen, and to evaluate the effect of the closed-loop management strategy.Methods: We undertook a descriptive study and risk analysis by the entry time, time of reporting, and local confirmed cases in countries of origin. The NAT were completed in Shenzhen Center for Disease Control and Prevention (CDC), ten district-level CDCs, and fever clinics.Results: A total of 86,844 people from overseas entered Shenzhen from January 1 to April 18, 2020; there were 39 imported COVID cases and 293 close contacts. The infection rate of people entering was 4.49‰ [95% Confidence interval (CI): 3.26‰-6.05‰]. Fourteen imported cases (35.9%) came from the UK, and nine (23.08%) came from the USA. People entering from the USA since March 9 or from the UK since March 13 are the high-risk population. As of July 17, there have been no new confirmed cases in Shenzhen for 153 days, and the numbers of confirmed case, close contacts, and asymptomatic cases are 0.Conclusions: The closed-loop management has been effective in preventing imported infection and controlling domestic relapse. The distribution of entry time and report time for imported cases overseas was similar. This shows that it is important to implement closed-loop management at the port of entry. [ABSTRACT FROM AUTHOR]

Considering the height and horizontal separations between stations, we propose a method to regionally model the tropospheric delay. The zenith tropospheric delay (ZTD) is separated into vertically-correlated and horizontally-correlated components, which are to be regionally modeled respectively. A more accurate ZTD is thereby interpolated at the rover station, and enhanced ZTD constraints can be provided for precise point positioning (PPP). A new constraint of the ZTD interpolation error is proposed and assessed. The results show that the linear correlation between ZTD after separation and the height of the station are further enhanced, with the mean correlation coefficient reaching up to 0.99. The RMS value of the ZTD obtained from undifferenced and uncombined PPP with fixed station coordinates is less than 6.5 mm. The new method is compared with conventional modeling methods and the results show that the new zenith tropospheric delay modeling method is superior to other methods, yielding a RMS value within 1 cm. Simulated kinematic positioning experiments for five different elevation cutoff angles from 10° to 50° are performed to evaluate the performance of the new method. Experimental results show that the new method can effectively improve the convergence and positioning accuracy. The systematic deviations of the vertical component for the higher cutoff angle solution can be significantly improved by the new method. [ABSTRACT FROM AUTHOR]

Background: Retinocytoma is a rare benign retinal tumor associated with variants in the RB1 gene. Ophthalmoscopic features can include a translucent retinal mass, calcification, retinal pigment epithelial alteration and chorioretinal atrophy. Methods: Detailed ophthalmological examinations were performed in a Chinese patient with retinocytoma and his daughter with bilateral retinoblastoma. Sanger sequencing was performed to detect RB1 genetic variants in the patient, his daughter and tumor tissue from his daughter. Results: A 33‐year‐old man presented with poor vision and strabismus in the right eye since childhood. Fundus examination revealed a round yellow‐white lesion stretching from the nasal side of the optic disc to the temporal periphery of the right eye. Sequencing result identified a reported variant (c.658C>G, p.Leu220Val) in the RB1 gene (NM_000321.2) of DNA extracted from peripheral blood of the patient and his daughter. The missense variant was also found in the tumor tissue from his daughter. Conclusions: We report detailed clinical features and genetic analysis of a case with unilateral retinocytoma. Retinocytoma has a wide range of clinical phenotypes; genetic testing is therefore a useful tool for the diagnosis of atypical cases. [ABSTRACT FROM AUTHOR]

Background: Circulating microRNAs (miRNAs) have become reliable sources of non‐invasive biomarkers for cancer diagnosis. Identification of promising miRNA biomarkers in plasma might benefit a lot to the detection of nasopharyngeal carcinoma (NPC). Methods: The Exiqon miRNA qPCR panel was used in the screening stage to identify candidate miRNAs, which were further verified by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in the following three stages among plasma samples from 200 NPC patients and 189 healthy donors (as normal controls [NCs]). The identified miRNAs were further explored in tissue specimens (48 NPC vs 32 NCs) and plasma exosomes (32 NPC vs 32 NCs). Survival analyses were ultimately conducted by Cox regression models and Kaplan‐Meier curves using log‐rank tests. Results: We identified a 7‐miRNA signature including let‐7b‐5p, miR‐140‐3p, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, miR‐20b‐5p, and miR‐205‐5p in plasma for NPC diagnosis after four‐stage validation. The areas under the receiver operating characteristic curve (AUCs) for the signature were 0.879, 0.884, 0.921, and 0.807 for the training, testing, external validation stage, and the combined three stages, respectively. In NPC tissues, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, and miR‐205‐5p were consistently up‐regulated while let‐7b‐5p and miR‐140‐3p were significantly down‐regulated compared to NCs. However, none of the seven identified miRNAs were dysregulated in plasma‐derived exosomes in NPC patients. As to survival analysis, none of the seven miRNAs seemed to be associated with NPC prognosis. Conclusion: We identified a 7‐miRNA signature in plasma as promising non‐invasive biomarkers for NPC detection. [ABSTRACT FROM AUTHOR]

Having a reasonable environmental management system is key to achieve regional green development. This article integrates environmental decentralization into an environmental/economic analytical framework, introducing a fiscal decentralization indicator to explore the mechanism of environmental decentralization and regional green development, and then tests this concept using Chinese provincial penal data. The results show that the spillover effect of green development is significant: Improving regional green development will promote green development in neighboring regions. At the national level, different categories of environmental decentralization have different effects, and these can also affect green development through both direct and indirect paths. There is also a positive interaction mechanism between these two variables. Moreover, the interaction between environmental and fiscal decentralization has a negative effect on regional green development, with the impact varying across regions. These findings play an important role in green development, industrial transformation, and advancement, especially in China. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers in females. Since early detection can bring prognosis benefit, discovery of novel noninvasive biomarkers for BC diagnosis is in urgent need. In this four‐phase study, we profiled miRNA expression in plasma samples from a total of 257 BC patients and 257 normal controls (NCs). Exiqon miRNA qPCR panel was used to select candidate miRNAs in the screening phase which were further analyzed using qRT‐PCR in the following training, testing and external validation phases. Finally, we identified five plasma miRNAs (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) whose expression levels were significantly different between BC patients and NCs. A 5‐miRNA panel in plasma with high sensitivity and specificity was then constructed to detect BC. The areas under the receiver‐operating characteristic curves (AUCs) of the panel were 0.683, 0.966, 0.978 for the training, testing and external validation sets, respectively. Expression of the identified miRNAs was further analyzed among 32 pairs of BC tissue and the adjacent normal tissue samples as well as plasma‐derived exosome samples from 32 BC patients vs 32 NCs. Let‐7b‐5p was contrarily down‐regulated in BC tissue. In exosomes samples, only miR‐122‐5p was significantly up‐regulated as in plasma for BC patients. In conclusion, we identified a 5‐miRNA plasma panel (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) that could serve as a promising biomarker for BC detection. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) has posed a great health threat to a growing number of people all over the world. Detection of serum miRNAs, being sensitive, noninvasive, and easy to obtain, has a great potential of being a novel screening method for PC patients. In this study, we investigated miRNA expression levels in serum by qRT‐PCR. The study was divided into four phases: the screening, training, testing, and external validation stage. We firstly chose candidate miRNAs using Exiqon panels in the screening phase. Then, a total of 129 PC serum samples and 107 normal controls (NCs) were further analyzed in the following training and testing phases to identify differently expressed miRNAs. A cohort of 30 PC serum samples vs 30 NCs was used to confirm the diagnostic value of the identified miRNAs in the external validation phase. Moreover, miRNA expressions in additional 44 PC tumor tissue samples and the matched adjacent normal tissue samples as well as 32 pairs of serum‐derived exosomes samples were also further explored. As a result, we identified six significantly upregulated miRNAs in the serum of PC: let‐7b‐5p, miR‐192‐5p, miR‐19a‐3p, miR‐19b‐3p, miR‐223‐3p, and miR‐25‐3p. A six‐miRNA panel in serum was then established. The area under the receiver operating characteristic curves (AUC) for the panel was 0.910 for the combined training and testing phases, which showed higher diagnostic value than the individual miRNA. Prognostic value prediction using Cox's proportional hazards model and Kaplan‐Meier curves showed that increased serum miR‐19a‐3p was closely related to worse overall survival (OS). In addition, significant upregulation of miR‐192‐5p, miR‐19a‐3p, and miR‐19b‐3p was observed in both PC tissue and serum‐derived exosomes samples. In conclusion, we identified a six‐miRNA (let‐7b‐5p, miR‐192‐5p, miR‐19a‐3p, miR‐19b‐3p, miR‐223‐3p, and miR‐25‐3p) panel in the serum for PC early and noninvasive diagnosis. [ABSTRACT FROM AUTHOR]

Gemin5 acts as a U1 small nuclear RNA (snRNA)‐binding protein in U1 small nuclear ribonucleic protein (snRNP) biogenesis. Here, we report a role for Gemin5 in unassembled U1 snRNP disposal under survival of motor neuron (SMN) protein‐deficient conditions. We demonstrate that non‐Sm protein‐associated U1 snRNA and U1A are enriched in cytoplasmic granules and colocalize to P bodies in SMN‐deficient cells. Immunoprecipitation assays show increased associations of the U1 snRNP component U1A with P body components and Gemin5 in SMN‐deficient cells. More importantly, Gemin5 knockdown eliminates the unassembled U1 snRNP granules and rescues U1 snRNA levels in SMN‐deficient cells. Taken together, our study provides direct evidence that Gemin5 is involved in unassembled‐U1 snRNA disposal under conditions of SMN deficiency. [ABSTRACT FROM AUTHOR]

In this study, Moringa oleifera leaves (MOL) were fermented with or without pyroligneous acid (PA) for 3, 7, 14, and 30 days. PA addition enhanced the contents of acetic acid and true protein (P < 0.01) and decreased pH (P < 0.01) and the contents of coliform bacteria, nonprotein nitrogen (P < 0.01), and ammonium nitrogen (P < 0.01). With the addition of PA, the abundance of Lactobacillus increased, but the abundance of Enterobacter decreased. A total of 754 metabolites were identified. In the MOL fermented with PA, the contents of apigenin, arbutin, 2-methoxy-4-vinyl phenol, and 4-methoxy cinnamic acid increased, while the content of skatole decreased compared with the contents for the MOL fermented without PA. The detected metabolites were correlated with bacterial communities, especially Lactobacillus and Weissella. In conclusion, the addition of PA improves the fermentation quality and protein preservation and affects the microbial communities and metabolites of fermented MOL. • Pyroligneous acid (PA) improved the fermentation quality of Moringa oleifera leaves. • PA increased the abundance of Lactobacillus and decreased that of Enterobacter. • PA changed the metabolites during the fermentation of M. oleifera leaves. • The metabolites were strongly correlated with Lactobacillus and Weissella. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenocarcinoma (PAAD) remains a lethal malignancy making the detection of novel prognostic biomarkers urgent. Limited studies have investigated the predictive capability of immune checkpoints in PAAD. Method: Gene expression data and correlative clinical information of PAAD cohort were obtained from public databases, including TCGA, ICGC, GTEX and GEO databases. Risk factors were screened and used to establish a risk score model through LASSO and Cox regression analyses. The prognostic ability of the risk score model was demonstrated. The association between risk score with immune cells infiltration, immune checkpoint genes expression, immunogenic cell death, somatic mutations and signaling pathways enrichment were analysed. scRNA-seq data were collected to confirmed the immune checkpoints expression in PAAD samples. The prognosis prediction ability of OX40/TNFRSF4 was identified. The mRNA and protein expression of OX40 in our clinical specimens were examined by RT-PCR and IHC method and its prognosis ability was verified. Results: First of all, the difference of immune microenvironment between pancreatic cancer and adjacent tissues was shown. A risk score system based on three immune checkpoints (OX40, TNFSF14 and KIR3DL1) was established. The risk score model was an independent prognostic factor and performed well regarding overall survival (OS) predictions among PAAD patients. A nomogram was established to facilitate the risk model application in clinical prognosis. Immune cells including naive B cells, CD8+ T cells and Tregs were negatively correlated with the risk score. The risk score was associated with expression of immune checkpoint genes, immunogenic cell death related genes and somatic mutations. Glycolysis processes, IL-2-STAT5, IL-6-STAT3, and mTORC1 signaling pathways were enriched in the high-risk score group. Furthermore, scRNA-seq data confirmed that TNFRSF4, TNFSF14 and KIR3DL1 were expressed on immune cells in PAAD samples. We then identified OX40 as an independent prognosis-related gene, and a higher OX40 expression was associated with increased survival rate and immune environment change. In 84 PAAD clinical specimens collected from our center, we confirmed that higher OX40 mRNA expression levels were related to a good prognosis. The protein expression of OX40 on tumor-infiltrating immune cells (TIICs), endothelial cells and tumor cells was verified in PAAD tissues by immunohistochemistry (IHC) method. Conclusions: Overall, our findings strongly suggested that the three-immune checkpoints score system might be useful in the prognosis and design of personalized treatments for PAAD patients. Finally, we identified OX40 as an independent potential biomarker for PAAD prognosis prediction. [ABSTRACT FROM AUTHOR]

In this paper, the network real-time kinematic (NRTK) positioning method based on undifferenced (UD) observation corrections (abbreviated as URTK) are described, in which instantaneous ambiguity resolution can be carried out within rover's precise point positioning (PPP) software, thus achieving position solutions equivalent to NRTK. The URTK method transforms the fixed double-differenced (DD) ambiguities of the reference network into UD ambiguities. With the transformed ambiguities, the residuals of the UD observation are used for interpolating the corrections at the user side. This approach breaks down the connections between the stations and satellites of the DD corrections in the current NRTK methods, such that corrections can be broadcast by the base station and automatically selected and optimized by a rover during the real-time kinematic (RTK) processing when the rover is transitioning into a more favorable subnetwork configuration, thus avoiding ambiguity reinitialization as a result of the change of reference. More importantly, this proposed approach provides a seamless integration of regional NRTK (PPP with regional augmentation) and global PPP-assisted kinematic surveying, which should be very useful for a wide range of applications. The key for realizing the improvements over standard NRTK is the development of a logical scheme that has the capability of rapid fixing of the single-differenced ionosphere-free ambiguity of the rover. Case studies at sea and on land demonstrate the advantages of this approach in terms of improvement in positioning accuracy, elimination of subsequent ambiguity reinitialization, and wider applications in the future. [ABSTRACT FROM AUTHOR]

Abstract: Nel-like protein 1 (NELL-1) is an osteoinductive molecule associated with premature calvarial suture closure. Here we identified apoptosis related protein 3 (APR3), a membrane protein known as a proliferation suppressor, as a binding protein of NELL-1 by biopanning. NELL-1 and APR3 colocalized on the nuclear envelope of human osteoblasts. NELL-1 significantly inhibited proliferation of osteoblasts co-transfected with APR3 through further down-regulation of Cyclin D1. The co-expression of NELL-1 and APR3 enhanced Ocn and Bsp expression and mineralization. RNAi of APR3 significantly reduced the differentiation effect of NELL-1. These findings suggest that the effects of NELL-1 on osteoblastic differentiation and proliferation are partly through binding to APR3. Structured summary of protein interactions: APR3 physically interacts with NELL1 by pull down (View interaction) APR3 and NELL1 colocalize by fluorescence microscopy (View interaction) NELL1 physically interacts with SMEK1 by phage display (View interaction) NELL1 physically interacts with EIF4B by phage display (View interaction) NELL1 physically interacts with APR3 by anti bait coimmunoprecipitation (View interaction) NELL1 physically interacts with EIF5B by phage display (View interaction) NELL1 physically interacts with DNTTIP2 by phage display (View interaction) NELL1 physically interacts with EEF1A1 by phage display (View interaction) NELL1 physically interacts with Nexilin by phage display (View interaction) NELL1 physically interacts with PLCG1 by phage display (View interaction) NELL1 physically interacts with APR3 by phage display (View interaction) NELL1 physically interacts with SLTM by phage display (View interaction) NELL1 physically interacts with SSRP1 by phage display (View interaction) NELL1 physically interacts with NOL10 by phage display (View interaction) [Copyright &y& Elsevier]

The multipath error is considered to be the most limiting factor for high precision positioning applications. The sidereal filtering (SF) method can be used to mitigate the multipath error in the observation domain, and it has been successfully applied in the multipath mitigation in global positioning systems (GPS) and regional BeiDou navigation satellite systems (BDS2). However, there are few reports on the SF method in other systems. The performance of the SF method relies on the explicit orbit repeat periods of satellites in diverse systems or even different types of constellations. It is therefore inconvenient to utilize the SF method for multi-GNSS multipath error mitigation. Alternatively, a space domain multipath error reduction method, which establishes the multi-point hemispherical grid model (MHGM) using the residuals of the double-differenced carrier phase observations in the ambiguity-fixed period, has been modified. It is an integrated model for multi-GNSS, without considering the diversity of different systems and constellations. To compare the performance of MHGM and SF from a multi-GNSS point of view, the determination method of orbit repeat periods via the broadcast ephemerides is summarized, and the SF method is extended to the global BeiDou navigation satellite system (BDS3) and Galileo navigation satellite system. Further test results show that the performance of MHGM and SF are comparable from the perspective of root mean squares (RMS) and the power spectrum analysis of double-differenced residuals, as well as the static positioning results. This implies that the space domain MHGM can obtain similar correction effects as the SF method in the observation domain, but the former is more flexible for modeling with various systems' data. In addition, the established MHGM using the data of multi orbit periods demonstrates a better performance compared with that of only one orbit period, and an average improvement of 13.1% in the RMS of the double-differenced residuals can be achieved. [ABSTRACT FROM AUTHOR]

Recent studies have shown that the energy release capacity of Polytetrafluoroethylene (PTFE)/Al with Si, and CuO, respectively, is higher than that of PTFE/Al. PTFE/Al/Si/CuO reactive materials with four proportions of PTFE/Si were designed by the molding–sintering process to study the influence of different PTFE/Si mass ratios on energy release. A drop hammer was selected for igniting the specimens, and the high-speed camera and spectrometer systems were used to record the energy release process and the flame spectrum, respectively. The ignition height of the reactive material was obtained by fitting the relationship between the flame duration and the drop height. It was found that the ignition height of PTFE/Al/Si/CuO containing 20% PTFE/Si is 48.27 cm, which is the lowest compared to the ignition height of other Si/PTFE ratios of PTFE/Al/Si/CuO; the flame temperature was calculated from the flame spectrum. It was found that flame temperature changes little for the same reactive material at different drop heights. Compared with the flame temperature of PTFE/Al/Si/CuO with four mass ratios, it was found that the flame temperature of PTFE/Al/Si/CuO with 20% PTFE/Si is the highest, which is 2589 K. The results show that PTFE/Al/Si/CuO containing 20% PTFE/Si is easier to be ignited and has a stronger temperature destruction effect. [ABSTRACT FROM AUTHOR]

The multipath effect on carrier-phase observations is related to the observational environment of the station, and cannot be eliminated or attenuated by the differential method. In the actual dam environment of deformation monitoring, multipath is very complicated. It is the main error source of BDS-2 for high precision data processing. In this paper, a new method called the multi-point hemispherical grid model (MHGM) is studied and evaluated. This method uses the hemispheric grid model to attenuate the influence of multipath errors. The effectiveness and improvement of the new method with respect to the popular sidereal filter (SF) method were assessed and verified by the actual dam monitoring data with only the BDS-2. The MHGM and SF approach calculates the multipath corrections from multi-days historical data, and then corrects the multipath error from the observations on the day of interest. Compared with the SF method, the MHGM can also effectively provide a graphical display of multipath error interference around the stations, which matches the surrounding observation environment. The results show that the double-differenced (DD) residuals of the MHGM for GEO/IGSO and MEO satellites are slightly better than those of SF, but the RMS of MHGM for GEO/IGSO+MEO DD residuals is improved by about 17.0%. The performance of the MHGM method for different satellite constellations is consistent and not affected by the different orbital repeat times, which could solve the "zero mean" assumption problem of the SF method. Meanwhile, the RMS of static with a 2 h interval and kinematic positioning errors of the MHGM method in the horizontal and vertical direction can be up to 1.7, 3.6 and 2.4, 8.1 mm, respectively. The MHGM model could avoid the multipath reference problem caused by different orbital repetition periods, making it more suitable for the combined multipath modeling of BDS-2 and BDS-3. [ABSTRACT FROM AUTHOR]

Broussonetia papyrifera has increasingly been used as a high-quality feedstuff for ruminants due to its advantageous characteristics. The storage temperature can influence the fermentation quality of silage; however, the effect of temperature on B. papyrifera leaves (BPL) silage has not been reported. In the present study, the fermentation quality and bacterial community of BPL, stored at 15 °C and 30 °C, were investigated during ensiling (day 3, 7, 14, 30) with or without Lactobacillus plantarum strain (LP) added. The pH and the coliform bacteria counts were significantly lower in silage stored at 30 than 15 °C (p < 0.01), while the lactic acid content increased significantly (p < 0.05). Adding LP decreased the dry matter loss, pH, coliform bacteria count, and ammonia-N and butyric acid contents at 30 °C. The relative abundance of Lactobacillus increased, while the bacterial diversity decreased in the silage stored at 30 °C when LP was added. During silage, the high abundance of Lactobacillus decreased gas and carbon dioxide (CO2) production, and the lowest gas and CO2 production were detected in silage stored at 30 °C when LP was added. In conclusion, adding LP and storing it at 30 °C could effectively improve the quality of BPL silage. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the most common malignancies in developed countries. The present study aimed to identify the role of secretoglobin family 2A member 1 (SCGB2A1) expression in uteri corpus endometrial carcinoma (UCEC) from The Cancer Genome Atlas (TCGA) database, and determine the SCGB2A1-associated downstream signaling pathways. The clinicopathological characteristics and gene expression data were downloaded from TCGA database. The Kaplan-Meier method and Cox multivariate model were used for survival analysis. Logistic regression was used to analyze the association between the clinicopathological features and SCGB2A1 expression. For validation, data of SCGB2A1 mRNA expression and protein expression were obtained and then survival analysis was performed for 47 patients with endometrial cancer from the Fudan University Shanghai Cancer Center (FUSCC). In TCGA dataset, SCGB2A1 expression was significantly higher in tumor tissues (n=528) compared with normal tissues (n=23, P<0.001). The decrease in SCGB2A1 expression in UCEC was significantly associated with age at diagnosis, high tumor grade, residual tumor, positive peritoneal cytology, pelvic lymph node metastasis, para-aortic lymph node metastasis and advanced clinical stage with P<0.05. In the multivariate analysis, SCGB2A1 expression was identified as an independent prognostic factor. In the FUSCC validation set, low SCGB2A1 expression was also associated with worse survival compared with high expression in endometrial cancer (P<0.001). Gene Set Enrichment Analysis revealed that SCGB2A1 may be involved in tumor proliferation and cell cycle regulation. In conclusion, SCGB2A1 may have an important role in the prognosis of UCEC, and has value as a new target for novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

The multipath effect is a crucial error source caused by the environment around the station and cannot be eliminated or mitigated by differential algorithms. Theoretically, the maximum value for the carrier phase is a quarter the wavelength, i.e., about 4.8 cm for the GPS L1 signal. Considering the increasing demands of high-precision applications, the multipath error has become a major factor affecting the accuracy and reliability of GPS millimeter-level data processing. This paper proposes a multi-point hemispherical grid model (MHGM) to mitigate the multipath effect. In this method, the hemisphere centered on each station is divided into a grid, and the multipath error at the station is estimated based on the parameterization of the grid points. The double-differenced (DD) observed-minus-calculated (OMC) values on some previous days are treated as the observation values to model the present multipath error. Contrary to the present methods which rely much on the platform of data collection and processing, MHGM can be potentially applied to GPS data processing with the existing hardware and software. Experiments in high-multipath and low-multipath environments are designed by mounting a baffle or not. The experimental results show that MHGM is effective in mitigating the multipath effect. When using data from the previous day, an average improvement of about 63.3% in the RMS of DD OMC can be made compared with that without correction, and this is basically consistent with the sidereal filtering (SF) method which is 63.0%. Furthermore, the effectiveness of the above two methods is better than that of the empirical site model (ESM). The kinematic positioning results are also basically consistent with the statistical results of the RMS values of DD OMC. Historical data from more than one day can more explicitly and effectively model the MHGM. Furthermore, compared with the SF method, the MHGM can be used not only to mitigate the multipath error, but also to orientate the sources of the multipath error around the station, and give guidance in the physical elimination of these sources. [ABSTRACT FROM AUTHOR]

The tripole vector antenna comprises three orthogonal dipole antennas, so it could completely capture all the electric field of the incident electromagnetic (EM) wave. Then, the electric field information could be used to estimate the direction of arrival (DOA) of the EM wave if two conditions are satisfied. One is that there exists only one single EM wave in space. The other is that the EM wave is elliptically or circularly polarized. The new estimation method obtains two snapshot vectors through the output of a tripole antenna and computes their cross-product vector. Furthermore, the direction of the cross-product vector is used to estimate the DOA of the EM wave directly. We analyze the statistical characteristics of the DOA estimation error to prove that the new scheme is an asymptotic unbiased estimation. Furthermore, unlike the existing Multiple Signal Classification (MUSIC)-based algorithms, the proposed approach only need one tripole vector antenna instead of an antenna array. Meanwhile, the new method also outperforms existing MUSIC-based algorithms in the term of computational complexity. Finally, the performance and advantages of the proposed method are verified by numerical simulations. [ABSTRACT FROM AUTHOR]

Objective: A type of rodent called a zokor causes great harm to agriculture and forestry production due to its large and sophisticated diet. As this rodent lives subterrane for most of its life, researchers know little about its dietary habits. Further understanding of its diet is important for developing green and sustainable control strategies for the zokor. Methods: Chloroplast trnL gene and internal transcription spacer 1 primers were selected for high-throughput sequencing of stomach contents of captured zokor by DNA metabarcoding. Results: A total of 25 zokors were selected, the food list of 32 families, 80 genera, and 154 species was obtained. At the family level, it was found that zokors mainly fed on Asteraceae, Poaceae, Rosaceae, Pinaceae, Brassicaceae, and Apiaceae. At the genus level, zokors mainly fed on Echinops, Littledalea, Artemisia, Picea, Cirsium, and Elymus. The diet alpha diversity of Eospalax cansus was slightly higher than that of Eospalax cansus (P>0.05). The zokor's diet is highly phconsistent with the resources of its habitat. Most food choices tend to be the same between the two zokors. They fed primarily on Calamagrostis, Cirsium, Echinops, Medicago, Sanguisorba, and Taraxacum. Zokors mainly fed on the roots of perennial herbs, which are important source of energy. Conclusion: High-throughput sequencing-based DNA metabarcoding technology has effectively revealed the diet of zokors and indicated that zokors are food generalists. [ABSTRACT FROM AUTHOR]

• Fe2+-activated NaOCl could effectively degrade Carbamazepine (CBZ) in the soil system. • The effects of operation factors on the Fe2+/NaOCl process were investigated. • Reaction mechanisms for CBZ degradation in soil were proposed. • Microbial community in soil system was negatively affected by Fe2+/NaOCl treatment. The existence of carbamazepine (CBZ) in soil environment has been continuously reported and efficient elimination techniques are imperative. This study investigated the feasibility and the optimal conditions of CBZ degradation in soil by using Fe2+-activated hypochlorite (NaOCl). The Fe2+/H 2 O 2 , Fe2+/persulfate and Fe2+/NaOCl systems were applied to degrade CBZ under different initial soil pH conditions, of which Fe2+/NaOCl system achieved a higher CBZ removal rate over a wider pH range. The results indicated that 94.5% of CBZ could be degraded after 4 h when NaOCl concentration was 75 mmol kg−1 at Fe2+/NaOCl molar ratio of 1:1, and the reaction followed pseudo-first-order model. The CBZ removal efficiency could be improved with the increasing of NaOCl dosage. The reduction of initial CBZ concentration had a dual effect on CBZ removal efficiency at a fixed NaOCl dosage. Raising the temperature could considerably speed up the reaction. The high liquid to soil ratio, excessive humic acid and inorganic anions (Cl−, HCO 3 −) were not conducive to CBZ removal. Electron Spin Resonance (ESR) confirmed that the Fe2+/NaOCl system yield more hydroxyl radicals (HO) than that of NaOCl alone for CBZ degradation. The transformation pathways were proposed for CBZ degradation based on the identified intermediates. The investigation with soil surface morphology and mineral composition (Fe, Mn, Cu and Zn) showed no significant differences between the original and the treated soil samples, while the soil microbial community was negatively affected. [ABSTRACT FROM AUTHOR]

• The study identified a five-microRNA signature in serum for nasopharyngeal carcinoma diagnosis. The AUC values are impressive with high sensitivity and specificity. • Comprehensive analysis in tissue specimens and exosomes samples were further conducted to bring deeper understanding of the identified miRNAs. • The candidate miRNAs list generated in the screening stage was selected via the application of the Exiqon miRNA qPCR panel, which is more suitable for preliminary screening of miRNA in peripheral blood samples. Circulating microRNAs have become reliable sources of non-invasive biomarkers for cancer diagnosis. miRNA expression analysis in blood circulation for the identification of novel signatures might assist the early detection of nasopharyngeal carcinoma (NPC) patients. In the screening stage, the Exiqon miRNA qPCR panel was applied for the selection of candidate miRNAs. Serum samples taken from 208 NPC patients and 238 healthy donors (as normal controls (NCs)) were assigned to into the following three stages (training (30 NPC VS. 30 NCs), testing (138 NPC VS. 166 NCs) and external validation stage (40 NPC VS. 42 NCs)) for further confirmation of differently expressed miRNAs using qRT-PCR. The identified miRNA signatures were further explored in tissue specimens (48 NPC VS. 32 NCs) and serum-derived exosomes samples (32 NPC VS. 32 NCs). Five miRNAs in serum including let-7b-5p, miR-140-3p, miR-192-5p, miR-223-3p and miR-24-3p were found to be significantly up-regulated in NPC patients compared to NCs. The five identified miRNAs were further combined into one panel and the areas under the receiver operating characteristic curve (AUCs) for three independent stages were 0.910 (training), 0.916 (testing) and 0.968 (external validation), respectively. miR-192-5p and miR-24-3p were consistently up-regulated in NPC tissues while let-7b-5p and miR-140-3p were conversely down-regulated. In serum-derived exosomes samples, no expression difference was observed between NPC patients and NCs. A five-miRNA signature was identified in serum to be potential biomarkers for NPC detection. [ABSTRACT FROM AUTHOR]

• MiR-188-3p, miR-500a-5p and miR-501-5p in plasma were found to be significantly up-regulated in BC patients. • MiR-188-3p, miR-501-3p, miR-502-3p, miR-532-3p and miR-532-5p in serum were also observed to be up-regulated in BC patients. • The expression levels of miR-188-3p presented a trend of positive correlation between plasma and serum samples. • A three-miRNA panel in plasma and a five-miRNA panel in serum were established. • The two panels showed high diagnostic value in discriminating BC patients at different stages from HCs. [ABSTRACT FROM AUTHOR]

Background: Recent progressions in CAR-T cell therapy against pancreatic ductal adenocarcinoma (PDAC) remain disappointing, which are partially attributed to the immunosuppressive microenvironment including macrophage-mediated T cell repletion. Methods: We first characterized the expression patterns of macrophage-relevant chemokines and identified CXCR2 as the key factor regulating T cell trafficking and tumor-specific accumulation in PDAC microenvironment. After that, we synthesized and introduced a CXCR2 expression cascade into Claudin18.2 CAR-T cells and compared the behaviors of CAR-T cells in vitro and in vivo. The therapeutic potential of CXCR2 CAR-T was evaluated in two different allogeneic models: subcutaneous allografts and metastatic PDAC models. Results: The results showed that CXCR2 CAR-T not only reduced the size of allografted PDAC tumors, but also completely eliminated the formation of metastases. Lastly, we investigated the tumor tissues and found that expression of ectopic CXCR2 significantly improved tumor-targeted infiltration and residence of T cells and reduced the presence of MDSCs and CXCR2 + macrophages in PDAC microenvironment. Conclusion: Our studies suggested that ectopic CXCR2 played a significant and promising role in improving the efficiency of CAR-T therapy against primary and metastatic PDAC and partially reversed the immune-suppressive microenvironment. [ABSTRACT FROM AUTHOR]

As lamella and porous materials, the failure of clay soil is closely related to the microscale friction features between nano minerals sheets. This study delves into the microscale interface stick-slip friction behavior of clay minerals, with a particular focus on kaolinite and halloysite models, under varying hydrostatic pressure conditions. The research unveils several significant discoveries. Firstly, under hydrostatic pressure, the mechanical properties of clay minerals perpendicular to the mineral platelet weaken, accompanied by a gradual reduction in the space occupied by interlayer water molecules. As pressure increases, these molecules assemble into "water molecular clusters", resulting in the formation of two or three layers of water molecular films. At 6 GPa, interlayer water nearly reaches a state of stagnation. Secondly, both kaolinite and halloysite exhibit "stick-slip friction behavior" during shearing, with rising hydrostatic pressure intensifying interatomic interactions and augmenting shear stress fluctuations. Lastly, the calculated friction coefficients (μ) for the three systems (kaolinite –7 Å, halloysite –8.6 Å, and halloysite –10 Å) are 0.035, 0.048, and 0.033, respectively, while the friction angles (φ) are 2.270, 2.900, and 2.263. The cohesion values (C) for these systems, obtained through different methods, demonstrate consistency. These findings advance the understanding of clay mineral behavior under varying conditions and contribute valuable insights to the microscale failure mechanism of clay soil. [Display omitted] • Kaolinite and halloysite show "stick-slip behavior" during the shearing process. • Multi-films and "dot clusters" of water molecules were formed between nanoplatelets. • The confined interlayer water is stationary as the hydrostatic pressure increases. • Enhancement of atomic interactions and frictional stress fluctuations were developed. [ABSTRACT FROM AUTHOR]

Systems metabolic engineering, which integrates metabolic engineering with systems biology, synthetic biology, and evolutionary engineering, has revolutionized the sustainable production of fuels and materials through the creation of efficient microbial cell factories. Recent advancements in systems metabolic engineering targeting different biological components of the host cell have enabled the creation of highly productive microbial cell factories. This article provides a review of the recent tools and strategies used for enzyme-, genetic module-, pathway-, flux-, genome-, and cell-level engineering, supported by illustrative examples. Furthermore, we highlight recent trends in systems metabolic engineering, which involve the application of multiple tools discussed in this review. Finally, the paper addresses the challenges and perspectives of transitioning academic-level metabolic engineering studies to commercial-scale production. [Display omitted] • Efficient microbial cell factories are developed by systems metabolic engineering. • Recent advances in systems metabolic engineering tools and strategies are reviewed. • Examples of systems metabolic engineering for strain development are showcased. [ABSTRACT FROM AUTHOR]

We report a 36-year-old male patient died of V. vulnificus-induced septicaemia and multiple organ failure syndrome after oyster consumption at a restaurant. We isolated and identified V. vulnificus vv16015 from the patient's blood sample and antibiotic susceptibility tests indicated sensitivity to all 21 antibiotics. Oyster samples were subsequently collected from the restaurant's supplier and three strains of V. vulnificus were isolated. Whole genome sequencing and analysis revealed vv16015 to be distantly related to these strains and confirmed that V. vulnificus contamination was present in the seafood of the restaurant and supplier. Using a Galleria mellonella larvae infection model, the virulence of vv16015 was determined to be higher than that of comparison strains isolated from a surviving patient (vv15018) and an oyster (vv220015). The human and environment distribution of V. vulnificus in Shenzhen is sporadic and heterogeneous, and vv16015 is highly virulent compared to other strains. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems, especially type II (Cas9) systems, have been widely used in gene/genome targeting. Modifications of Cas9 enable these systems to become platforms for precise DNA manipulations. However, the utilization of CRISPR-Cas systems in RNA targeting remains preliminary. The discovery of type VI CRISPR-Cas systems (Cas13) shed light on RNA-guided RNA targeting. Cas13d, the smallest Cas13 protein, with a length of only ~930 amino acids, is a promising platform for RNA targeting compatible with viral delivery systems. Much effort has also been made to develop Cas9, Cas13a and Cas13b applications for RNA-guided RNA targeting. The discovery of new RNA-targeting CRISPR-Cas systems as well as the development of RNA-targeting platforms with Cas9 and Cas13 will promote RNA-targeting technology substantially. Here, we review new advances in RNA-targeting CRISPR-Cas systems as well as advances in applications of these systems in RNA targeting, tracking and editing. We also compare these Cas protein-based technologies with traditional technologies for RNA targeting, tracking and editing. Finally, we discuss remaining questions and prospects for the future. • RNA targeting and editing are becoming increasingly important • CRISPR-Cas systems are advancing for RNA targeting, tracking and editing • The type VI CRISPR-Cas systems are useful for RNA-guided RNA targeting • Use of Cas9 and Cas13 will advance RNA-targeting technologies [ABSTRACT FROM AUTHOR]

• Transmissibility of three variants was Omicron BA.2>Omicron BA.1 > Delta. • Omicron BA.2 variant has less pathogenicity than Omicron BA.1 and Delta variant. • Transmissibility in cycle threshold value should be discussed in further research. The Omicron BA.2 variant is probably the main epidemic strain worldwide at present. Comparing the epidemiological characteristics, transmissibility, and influencing factors of SARS-CoV-2, the results obtained in this paper will help to provide theoretical support for disease control. This study was a historical information analysis, using the R programming language and SPSS 24.0 for statistical analysis. The Geoda and Arc GIS were used for spatial autocorrelation analysis. Local spatial autocorrelations of the incidence rate were observed in Delta and Omicron BA.1 outbreaks, whereas Omicron BA.2 outbreaks showed a random distribution in incidence rate. The time-dependent reproduction number of Delta, Omicron BA.1, and Omicron BA.2 were 3.21, 4.29, and 2.96, respectively, and correspondingly, the mean serial interval were 4.29 days (95% confidence interval [CI]: 0.37-8.21), 3.84 days (95% CI: 0-8.37), and 2.77 days (95% CI: 0-5.83). The asymptomatic infection rate of cases in Delta, Omicron BA.1, and Omicron BA.2 outbreaks were 21.71%, 6.25%, and 4.35%, respectively. The Omicron BA.2 variant had the greatest serial interval, transmissibility, and transmission speed, followed by BA.1, and then Delta. Compared with Delta and Omicron BA.1 variants, the Omicron BA.2 variant may be less pathogenic and more difficult to control than Omicron BA.1 and Delta. [ABSTRACT FROM AUTHOR]

Masses for 664 single-lined hot subdwarf stars identified in LAMOST were calculated by comparing synthetic fluxes from spectral energy distribution with observed fluxes from a Virtual Observatory service. Three groups of hot subdwarf stars were selected from the whole sample according to their parallax precision to study the mass distributions. We found that He-poor sdB/sdOB stars present a wide mass distribution from 0.1 to 1.0 M ⊙ with a sharp mass peak at around 0.46 M ⊙, which is consistent with canonical binary model prediction. He-rich sdB/sdOB/sdO stars present a much flatter mass distribution than He-poor sdB/sdOB stars and with a mass peak at around 0.42 M ⊙. By comparing the observed mass distributions to the predictions of different formation scenarios, we concluded that the binary merger channel, including two helium white dwarfs (He-WDs) and He-WD + main-sequence mergers, cannot be the only main formation channel for He-rich hot subdwarfs, and other formation channels, such as the surviving companions from Type Ia supernovae, could also make impacts on producing this special population, especially for He-rich hot subdwarfs with masses less than 0.44 M ⊙. He-poor sdO stars also present a flatter mass distribution with an inconspicuous peak mass at 0.18 M ⊙. The similar mass– Δ RV max distribution between He-poor sdB/sdOB and sdO stars supports the scenario that He-poor sdO stars could be the subsequent evolution stage of He-poor sdB/sdOB stars. [ABSTRACT FROM AUTHOR]

X-linked ocular albinism (OA1) is an X-linked inherited disease characterized by hypopigmentation of the fundus and nystagmus. Our study performed mutation analysis of the G protein-coupled receptor 143 gene (GPR143) and assessed the clinical characteristics of OA1 in three Chinese families. Three novel mutations, c.333_360+14del42insCTT, c.276G>A (p.W92X), and c.793C>T (p.R265X), were identified in GPR143 by PCR followed by Sanger sequencing in these families. All affected individuals presented with nystagmus, photophobia, poor visual acuity, foveal hypoplasia and varying degrees of hypopigmentation of the fundus. The fundus of female carriers showed pigmented streaks alternating with hypopigmented streaks. These results allowed us to expand the spectrum of mutations in GPR143 and phenotypes associated with ocular albinism. [ABSTRACT FROM AUTHOR]

Abstract Whether plasma miRNAs could be used as novel non-invasive biomarkers in diagnosing papillary thyroid carcinoma (PTC) remains unknown. In this study, we designed a four-phase study to identify differentially expressed plasma miRNAs in Chinese PTC patients. Exiqon panel was initially utilized to conduct plasma miRNA profile (3 PTC pools VS. 1 healthy control (HC) pool; each 10 samples were pooled as 1 sample). The dysregulated miRNAs were then analyzed in the training (30 PTC VS. 30 HCs), testing (57 PTC VS. 54 HCs) and external validation phases (33 PTC VS. 30HCs). The identified miRNAs were further affirmed in benign nodules (2 nodular goiter (NG) pool VS. 1 HC pool). We also verified the expression of identified miRNAs in 17 matched malignant and normal tissue samples, NG plasma samples (29 PTC VS. 29 NG) and plasma exosomes (25 PTC VS. 25 HCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of the identified miRNAs. As a result, the screening phase demonstrated 30 dysregulated plasma miRNAs in PTC patients compared with HCs. After multiphase experiment processes, miR-346, miR-10a-5p and miR-34a-5p were found significantly elevated in PTC plasma samples relative to HCs. The areas under the ROC curve (AUC) of the three-miRNA panel for the training, testing and validation phases were 0.926, 0.811 and 0.816, separately. The panel could also differentiate PTC from NG with the AUC of 0.877. MiR-346 and miR-34a-5p but not miR-10a-5p were up-regulated in PTC tissues. And the three miRNAs showed consistently up-regulation in PTC plasma exosomes. In conclusion, our study established a three-miRNA panel in plasma with considerable clinical value in discriminating PTC from HC or NG. Highlights • Plasma miR-346, miR-10a-5p and miR-34a-5p were elevated in PTC patients relative to HCs. • The three-miRNA panel could differentiate PTC patients from NG patients or HCs. • MiR-346 and miR-34a-5p but not miR-10a-5p were elevated in tumor tissues to normal tissues. • All the three miRNAs were up-regulated in exosomes from PTC plasma samples compared to HCs. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the common malignant tumors in the head and neck, characterized by high malignancy, rapid growth and metastasis, high invasive ability, and high mortality. In recent years, surgery combined with chemotherapy or radiotherapy remains the preferred clinical treatment for OSCC, despite considerable advances in diagnostic and therapeutic techniques. Hence, new targeted therapy is urgently needed. Histone modification affects the function of massive cells through histone acetyltransferase and histone deacetylase. Accompanied by the progress of some diseases, especially tumors, these proteins often show abnormal functions, and by reversing these abnormalities with drugs or gene therapy, the cancer phenotype can even be restored to normal. As a result, they are potential drug targets. This article reviewed the role of the histone dynamic process of acetylation modifications and their associated active modifying enzymes in the pathogenesis and progress of OSCC. Moreover, we explored the value of histone acetylation modification as a potential therapeutic target and the new progress of related drugs in clinical treatment. [ABSTRACT FROM AUTHOR]

Background: To promote influenza vaccination coverage, a Chinese megacity, Shenzhen provides free influenza vaccination to its residents aged 60 years and above through community health centres (CHCs) since October 2016. A community health centre-based experiment was conducted by asking primary care physicians (PCPs) working in the intervention health centres to proactively recommend influenza vaccination to their patients aged 60 and above during their patients' visits. Methods: This study used an experimental design and a survey design. The experimental design evaluated the effect of PCP recommendation on influenza vaccination. A total of 24 CHCs were randomly selected as the intervention (involving 3814 participants) and control (3072 participants) group evenly. The intervention study period was during the 2017–2018 flu season. The 2016–2017 flu season was considered as the baseline comparison. The survey design examined changes in knowledge, attitude, and practice of influenza vaccination among older participants before and after the free influenza vaccination implementation. We randomly invited 1200 participants aged 60 and above during their visits to CHCs in October 2016 and followed them up until October 2017; among them, 958 participants completed the follow-up survey using the same questionnaire. Results: In the 2017–2018 flu season, 1,100 more patients got vaccinated in the intervention group under PCP recommendation compared with the 2016–2017 flu season. Among the 958 older adults in the post-implementation period, 77.5% had heard about the influenza vaccine, which was 24.7% higher than in the pre-implementation period; 84.8% of participants were aware where to take influenza vaccines, with the most improvement of 37.2% among all knowledge related questions; 62.5% of them agreed that patients with chronic diseases should have influenza vaccine, which was 19.1% higher than those being surveyed before the implementation period. About 83.6% of participants agreed older adults should have influenza vaccine, but there were still 58.4% who considered themselves too healthy to get vaccinated. Conclusion: PCP recommendation improved influenza vaccine uptake and knowledge, attitude, and practice levels regarding influenza vaccination among older adults. More health policies and health education should be made to raise vaccination willingness and improve vaccination coverage among older adults. [ABSTRACT FROM AUTHOR]

Auxin plays a critical role in organogenesis in plants. The classical auxin signaling pathway holds that auxin initiates downstream signal transduction by degrading Aux/IAA transcription repressors that interact with ARF transcription factors. In this study, 23 MoIAA genes were identified in the drumstick tree genome. All MoIAA genes were located within five subfamilies based on phylogenetic evolution analysis; the gene characteristics and promoter cis-elements were also analyzed. The protein interaction network between the MoIAAs with MoARFs was complex. The MoIAA gene family responded positively to NAA treatment, exhibiting different patterns and degrees, notably for MoIAA1, MoIAA7 and MoIAA13. The three genes expressed and functioned in the nucleus; only the intact encoding protein of MoIAA13 exhibited transcriptional activation activity. The shoot regeneration capacity in the 35S::MoIAA13-OE transgenic line was considerably lower than in the wild type. These results establish a foundation for further research on MoIAA gene function and provide useful information for improved tissue culture efficiency and molecular breeding of M. oleifera. [ABSTRACT FROM AUTHOR]

Methane emission from the ruminants is not only a significant amount of greenhouse gases contributing to climate change but also a reduction in feed efficacy. Mitigation of ruminal CH 4 emission is a great challenge for cleaner livestock production. It is difficult to reduce CH 4 production without any adverse effects on feed digestion. The present investigation was conducted to explore the sustainable mitigation of ruminal CH 4 production with positive effects on feed digestibility using Neolamarckia cadamba leaves extract (NE). Stylo was added and ensiled with or without 1% and 2% NE, and the silage was engaged in vitro ruminal fermentation. Metagenomics was used to analyze the microbial communities and functional genes. The results indicated that the addition of 1% and 2% NE decreased (P < 0.001) CH 4 production significantly and increased (P < 0.001) dry matter digestibility at the same time. The concentrations of volatile fatty acids were not altered by NE. Some genes related to glycoside hydrolases, glycosyl transferases, carbohydrate-binding modules were upregulated by 2%NE. The addition of NE showed little influence on the ruminal microbial community, but reduced (P < 0.05) the relative abundance of Methanobrevibacter , especially the Methanobrevibacter curvatus , which was positively correlated (correlation = 0.561, P = 0.011) with the ruminal CH 4 production. In CH 4 metabolism, genes related to the serine pathway were highly detected. The addition of NE inhibited (P < 0.05) CH 4 metabolism by downregulating the great majority of involved genes. In conclusion, the present study provides new insights into the pathway of CH 4 metabolism and useful information for understanding and controlling ruminal CH 4 production in livestock production. The addition of NE might be a sustainable option to reduce CH 4 while enhancing animal feed utilization efficiency. It could be used as a pronounced cleaner way for the ecosystem as well as livestock. [Display omitted] • Neolamarckia cadamba leaves extract (NE) increased digestibility of stylo silage. • Genes related to carbohydrate-active enzymes were upregulated by NE. • NE reduced CH 4 production by decreasing the abundance of Methanobrevibacter curvatus. • NE inhibited CH 4 metabolism by downregulating the great majority of involved genes. [ABSTRACT FROM AUTHOR]

Simple Summary: The swimming ability of fish plays a guiding role in the construction of fish passing facilities. However, it is not enough to know the swimming ability of fish. We need to know the behavior and energy consumption of fish in the process of movement, so as to determine the activity area and migration suitable for fish. Therefore, a video tracking program was used to record and analyze the motion of five test fish in a Brett-type flume during each velocity step. The results obtained the kinematic and dynamic parameters of fish. Secondly, we found that steady fish swimming is not entirely steady in flowing water, with swimming speed varying by 2.2% to 8.4% and increasing with flow velocity. Further, because energy expenditure increases with the cube of swimming speed, a slight excess in fish passage flow velocity could result in a disproportionately large decrease in the rate of passage success. Therefore, we recommend guarding against an excessive flow velocity in the main velocity zone and ensuring that resting pools along the passageway are adequate. Our characterization of the kinematics and dynamics of fish swimming provides important new information to consider when indices of swimming ability from controlled tank testing are applied to fish passage design. The swimming kinematics (how fish move) and dynamics (how forces effect movement) of Schizopygopsis malacanthus were investigated during the determination of U c r i t by stepped velocity testing. A video tracking program was used to record and analyze the motion of five test fish in a Brett-type flume during each velocity step. The findings fell into three groups: (1) Even when flow was uniform, fish did not swim steadily, with speeds fluctuating by 2.2% to 8.4% during steady swimming. The proportion of unsteady swimming time increased with water velocity, and defining steady and unsteady swimming statistically, in terms of the definition of standard deviation of instantaneous displacements, may have higher accuracy. (2) In steady swimming, the forward velocity and acceleration of fish were correlated with body length (p < 0.05), but in unsteady swimming the correlations were not significant. The maximum swimming speed (1.504 m/s) and acceleration (16.54 m/s2) occurred during unsteady swimming, but these measurements may not be definitive because of tank space constraints on fish movement and the passive behavior of the test fish with respect to acceleration. (3) Burst-coast swimming in still water, investigated by previous scholars as an energy conserving behavior, is not the same as the gait transition from steady to unsteady swimming in flowing water. In this study, the axial force of fish swimming in the unsteady mode was significantly higher (×1.2~1.6) than in the steady mode, as was the energy consumed (×1.27~3.33). Thus, gait transition increases, rather than decreases, energy consumption. Our characterization of the kinematics and dynamics of fish swimming provides important new information to consider when indices of swimming ability from controlled tank testing are applied to fish passage design. [ABSTRACT FROM AUTHOR]

Background: Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs. Methods: We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy. Results: The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup. Conclusions: Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study is to understand the oral mucosal immune status of cancer patients and to make clear whether antibacterial proteins such as salivary secretory immunoglobulin (SIgA) and lysozyme in saliva were influenced by patients’ health status and certain medical treatment therapy. Materials and Methods. This study included 221 patients with malignant tumor receiving antineoplastic treatment and 171 age- and gender-matched healthy controls. Results. The results showed that patients suffering malignant tumor had lower level of SIgA and higher level of lysozyme than healthy subjects (P<0.05). The SIgA level was significantly different among different cancer tumors, while the lysozyme level showed significant difference only between patients with digestive tract malignant tumor and hematopoietic system tumor. Pretreatment before transplantation for hematopoietic system tumor patients significantly affected the lysozyme level other than SIgA. SIgA level was affected by many factors such as age, therapy factors, and oral hygiene. Conclusion. Malignant tumor and the antineoplaston may weaken the patients’ oral mucosal immunity, influence levels of some salivary proteins, and decrease the level of SIgA, resulting in aggregation of oral bacteria and failure of clearing them from the oral cavity. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) displays a typical mucin expression pattern which is characterized by MUC1 positive, MUC2 negative, and MUC5AC positive. More and more evidences show that mucins are involved in the development of pancreatic diseases. However, the relationship between mucin expression and prognosis of PDAC patients has been controversial in the past decades; therefore, we aim to figure out the association of mucin expression with survival in PDAC patients who underwent radical resection.Methods: We performed immunohistochemistry (IHC) to detect the expression of MUC1, MUC2, and MUC5AC in resected PDAC specimens from Shanghai Cancer Center, Fudan University (FUSCC, n = 427) and obtained the corresponding clinical statistical data for retrospective study. Kaplan-Meier methods and Mantel-Cox tests were used to compare the survival curves, and the Cox regression model was employed for multivariate analyses to determine the independent risk factors. Survival analysis was also performed in the Queensland Centre for Medical Genomics (QCMG, n = 70) PDAC cohort to verify the conclusion.Results: Both the FUSCC cohort and the QCMG cohort demonstrated that MUC1 absence was significantly correlated with worse overall survival (OS). The presence of MUC2 showed marginal significance in predicting shorter OS of PDAC patients, while MUC5AC had no prognostic value. In the FUSCC cohort, MUC1 absence was associated with increased proportion of stage III PDAC (p = 0.011), and MUC1 absence and MUC2 presence were associated with tumour perineural aggression (p = 0.011 and p = 0.030, respectively). Multivariable adjusted hazard ratios (HRs) for mortality of MUC1 and MUC2 were 0.492 (95% CI: 0.274-0.883, p = 0.017) and 1.596 (95% CI: 1.061-2.401, p = 0.025), respectively.Conclusions: MUC1 absence or MUC2 presence is independently associated with poor OS among patients with resectable PDAC. MUC5AC absence tended to be associated with short-term death. [ABSTRACT FROM AUTHOR]

The global BeiDou Navigation Satellite System (BDS-3) has been formally operated together with the regional system (BDS-2) for more than one year. However, the different frequency numbers between BDS-2 and BDS-3 makes their integration a troublesome problem, especially when all available frequencies are taken into account. To make a comprehensive analysis of multi-frequency precise positioning models in BDS-2 and BDS-3, the popular real-time kinematic positioning is taken as an example for data processing. Since in general the reliable, successful and rapid ambiguity resolution is the key of an appropriate multi-frequency positioning model, the framework of multi-frequency ambiguity resolution (AR) is summarized first. The usual loose combined model for the joint BDS-2 and BDS-3 system is described. To make full use of the common frequencies B1I and B3I in BDS-2 and BDS-3, an improved combined model is proposed where both the loose combined mode and tightly combined mode are applied. The performance of ambiguity resolution (AR) and positioning precision are obtained from four short baselines with different lengths in the above two models and with different elevation masks. The comparison results show that: (1) Both the combined model and improved combined model can achieve nearly 100% AR success rate and correctly-fixed rate, as well as consistent centimeter level's fixed solution; (2) The improved combined model can obtain higher AR fixed rate and shorter time to first fix (TTFF) compared with the usual combined model, and the improvements can be up to 15% for the fixed rate and 37% for TTFF; (3) To achieve the largest AR fixed rate while keep reliable AR and precise positioning, a relative large elevation mask such as 30° is highly recommended for a joint BDS-2 and BDS-3 system with sufficient observed satellites. [ABSTRACT FROM AUTHOR]

Alternate day fasting (ADF), the most popular form of caloric restriction, has shown to improve metabolic health in preclinical subjects, while intrinsic network underpinning the process remains unclear. Here, it is found that liver undergoes dramatic metabolic reprogramming during ADF, accompanied surprisingly with unique complex II dysfunction attributing to suspended complex II assembly via suppressing SDHAF4, a recently identified assembly factor. Despite moderate mitochondrial complex II dysfunction, hepatic Sdhaf4 knockout mice present intriguingly improved glucose tolerance and systemic insulin sensitivity, consistent with mice after ADF intervention. Mechanistically, it is found that hepatocytes activate arginine‐nitric oxide (NO) biosynthesis axle in response to complex II and citric acid cycle dysfunction, the release of NO from liver can target muscle and adipocytes in addition to its autocrine action for enhanced insulin sensitivity. These results highlight the pivotal role of liver in ADF‐associated systemic benefits, and suggest that targeting hepatic complex II assembly can be an intriguing strategy against metabolic disorders. [ABSTRACT FROM AUTHOR]

The plant embryogenic callus (EC) is an irregular embryogenic cell mass with strong regenerative ability that can be used for propagation and genetic transformation. However, difficulties with EC induction have hindered the breeding of drumstick, a tree with diverse potential commercial uses. In this study, three drumstick EC cDNA libraries were sequenced using an Illumina NovaSeq 6000 system. A total of 7191 differentially expressed genes (DEGs) for embryogenic callus development were identified, of which 2325 were mapped to the KEGG database, with the categories of plant hormone signal transduction and Plant-pathogen interaction being well-represented. The results obtained suggest that auxin and cytokinin metabolism and several embryogenesis-labeled genes are involved in embryogenic callus induction. Additionally, 589 transcription factors from 20 different families were differentially expressed during EC formation. The differential expression of 16 unigenes related to auxin signaling pathways was validated experimentally by quantitative real time PCR (qRT-PCR) using samples representing three sequential developmental stages of drumstick EC, supporting their apparent involvement in drumstick EC formation. Our study provides valuable information about the molecular mechanism of EC formation and has revealed new genes involved in this process. [ABSTRACT FROM AUTHOR]

Mitochondrial epigenetics is rising as intriguing notion for its potential involvement in aging and diseases, while the details remain largely unexplored. Here it is shown that among the 13 mitochondrial DNA (mtDNA) encoded genes, NADH‐dehydrogenase 6 (ND6) transcript is primarily decreased in obese and type 2 diabetes populations, which negatively correlates with its distinctive hypermethylation. Hepatic mtDNA sequencing in mice unveils that ND6 presents the highest methylation level, which dramatically increases under diabetic condition due to enhanced mitochondrial translocation of DNA methyltransferase 1 (DNMT1) promoted by free fatty acid through adenosine 5'‐monophosphate (AMP)‐activated protein kinase (AMPK) activation. Hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impairs mitochondrial function and induces systemic insulin resistance both in vivo and in vitro. Genetic or chemical targeting hepatic DNMT1 shows significant benefits against insulin resistance associated metabolic disorders. These findings highlight the pivotal role of ND6 epigenetic network in regulating mitochondrial function and onset of insulin resistance, shedding light on potential preventive and therapeutic strategies of insulin resistance and related metabolic disorders from a perspective of mitochondrial epigenetics. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA). Methods: In this multicenter, randomized, sham‐controlled trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent‐to‐treat population, which included all randomized participants who had ≥1 post‐baseline measurement. Results: Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between‐group differences were 13.0% (97.5% confidence interval [97.5% CI] 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI −1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26. Conclusion: Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow‐up. [ABSTRACT FROM AUTHOR]