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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]

Thrombosis is the main cause of many cardiovascular diseases. The conventional pharmaceuticals used for preventing thrombosis can induce significant adverse side effects, especially bleeding risk. Hence, the development of more effective and safe antithrombotic agents is strongly demanded to improve clinical treatment. In order to rapidly screen and identify novel antithrombotic substances from natural marine products, a multi-target screening strategy is reported to quantify the antithrombotic activity with high-performance liquid chromatography – mass spectrometry (HPLC-MS). Five key thrombosis-related targets, including thrombin, coagulation factors Xa, XIa and XIIa and platelet phosphodiesterase 3, were selected to establish the multi-target antithrombotic activity screening assay. The Michaelis-Menten constants (Km) were 8.16 µM, 58.85 µM, 120.03 µM, 35.24 µM and 79.67 µM, respectively. Five known inhibitors, namely argatroban, rivaroxaban, benzamidine, 3-carboxamide-coumarinand, and milrinone, were used for validation. The reproducibility of the screening strategy was verified by calculating the overall average Z′ value, which was 0.88. Subsequently, this method was assessed by screening a small marine library of 78 compounds. Five coumarin compounds were selected, and their antithrombotic activities were further validated in standard assessments of enzyme inhibition and on the coagulometer. According to the validation, the multi-target assay based on dried blood spots and HPLC-MS was suitable for screening antithrombotic substances with considerable reliability. [ABSTRACT FROM AUTHOR]

[Display omitted] • The volatile compounds in the stems and leaves of Platostoma palustre exhibit differences. • The germplasm and ploidy of Platostoma palustre can be differentiated by its volatile compounds. • The combination of HS-GC–MS and e-nose can recognize stems and leaves of Platostoma palustre. • E-nose sensors and volatile compounds intensities exhibit correlation. Platostoma palustre (Mesona chinensis Benth or Hsian-tsao, also known as "Xiancao" in China), is an edible and medicinal plant native to India, Myanmar, and Indo-China. It is the main ingredient in the popular desserts Hsian-tsao tea, herbal jelly, and sweet herbal jelly soup. P. palustre is found abundantly in nutrient-rich substances and possesses unique aroma compounds. Variations in the contents of volatile compounds among different germplasms significantly affect the quality and flavor of P. palustre , causing contradiction in demand. This study investigates the variation in the volatile compound profiles of distinct ploidy germplasms of P. palustre by utilising headspace gas chromatography-mass spectrometry (HS-GC–MS) and an electronic nose (e-nose). The results showed significant differences in the aroma characteristics of stem and leaf samples in diverse P. palustre germplasms. A total of sixty-seven volatile compounds have been identified and divided into ten classes. Six volatile compounds (caryophyllene, α-bisabolol, benzaldehyde, β-selinene, β-elemene and acetic acid) were screened as potential marker volatile compounds to discriminate stems and leaves of P. palustre. In this study, leaves of P. palustre showed one odor pattern and stems showed two odor patterns under the influence of α-bisabolol, acetic acid, and butyrolactone. In addition, a correlation analysis was conducted on the main volatile compounds identified by HS-GC–MS and e-nose. This analysis provided additional insight into the variations among samples resulting from diverse germplasms. The present study provides a valuable volatilome, and flavor, and quality evaluation for P. palustre , as well as new insights and scientific basis for the development and use of P. palustre germplasm resources. [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: Several studies have demonstrated that microRNAs (miRNAs) and target mRNAs are associated with different frequencies of microsatellite instability. OBJECTIVE: The study aimed to elucidate the profiles of miRNAs and target mRNAs expression and their associations with the phenotypic hallmarks of microsatellite instability in colorectal cancers (CRC) by integrating transcriptomic, immunophenotype, methylation, mutation, and survival data. METHODS: Differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were screened out and then the miRNA-mRNA regulatory pairs were identified through two databases. We verified that the expression levels were detected in 40 microsatellite instable (MSI) and 40 microsatellite stable (MSS) CRC samples and used the logistic regression and the Cox regression method to evaluate the diagnostic and prognostic value of negative regulatory pairs respectively. RESULTS: The best diagnostic model that combines miR-31-5p, PLAGL2, miR-361-5p, and RAB27B, which were associated with immune microenvironment, tumor mutation burden (TMB), and overall DNA methylation, could significantly predict microsatellite instability in colon tissues. MiR-31-5p and RAB27B could also predict the overall survival of MSS CRCs. CONCLUSION: This study generated a predictive model of the combination of miRNAs and mRNAs to distinguish MSI versus MSS CRCs and elaborated their potential molecular mechanisms and biological functions. [ABSTRACT FROM AUTHOR]

Objective To observe the clinical effect of acupuncture on postprandial distress syndrome (PDS) with spleen-stomach qi deficiency. Methods A retrospective analysis was conducted in 108 eligible PDS patients, with 55 cases in the acupuncture group and 53 cases in the sham acupuncture group. The patients in the acupuncture group were treated by acupuncture at Baihui (DU20), Danzhong ( RN17), Zhongwan ( RN12), Qihai ( RN6 ), Tianshu ( ST25 ), Neiguan ( PC6 ), Zusanli ( ST36 ), Gongsun(SP4) and Taibai(SP3). A superficial skin penetration at non-acupoints was performed in the sham acupuncture group. The patients in both groups were treated for 3 sessions (20 minutes per session) per week for 4 weeks, and were followed up 12 weeks after the last session. The changes of Symptom Index of Dyspepsia ( SID), Nepean dyspepsia index ( NDI) and Hospital Anxiety and Depression Scale(HADS) scores were compared between the two groups after the last session and 12 weeks after the treatment, so as to evaluate the efficacy and safety. Results After 4 weeks of treatment, the effective rate of the acupuncture group was 72. 7 %, higher than 45. 3 % of the sham acupuncture group ( P < 0. 05 ), and the descender of SID and NDI scores of the acupuncture group were greater than those of the sham acupuncture group (P <0. 05 ) and lasted for 12 weeks after treatment (P <0. 05 ) . After 4 weeks of treatment, the descender of HADS score in the acupuncture group was greater than that of the sham group (P < 0. 05), but there was no significant difference between the two groups during follow-up period. No serious adverse events were reported during the study period. Conclusion Among PDS patients with spleen-stomach qi deficiency, acupuncture could reduce the symptoms of indigestion, improve the quality of life, with sustained efficacy over 12 weeks in patients who have received acupuncture treatment for 4 weeks, three times each week. Acupuncture seems to alleviate the patients anxious and depressive emotions, but this effect does persist when the treatment ends. [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]

BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC. [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]

• By improving INNOV, EDEX and degree of openness, the interaction of labor quality and production technology can be better. • Provinces with a moderate CDD should make efforts to evaluate new technology and decide how much subsidies will be given. • Improving the degree of population concentration of the central and western provinces with very low CDD can increase CDD. Effective factor inputs and sustainable industrial development are essential for supply-side structural reforms, which are mainly based on the coordinated development of labor quality and production technology. This study explores the coordinated development of labor quality and production technology, using provincial data from China. The results show an interaction between labor quality and production technology. However, China's coordinated development of labor quality and production technology is low because of issues including its innovativeness, education expenditure, technology value, and the openness of the economy. [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]

A growing body of research suggests that gut microbiota is inextricably linked to host health and disease，so we are committed to finding more probiotic resources that are beneficial to human health. This study evaluated the probiotic properties of Lactobacillus sakei L-7 isolated from home-made sausages. The basic probiotic properties of L. sakei L-7 were evaluated through in vitro tests. The strain showed 89% viability after 7 h of digestion in simulating gastric and intestinal fluid. The hydrophobicity, self-aggregation and co-aggregation of L. sakei L-7 showed it had a strong adhesion ability. C57BL/6 J mice were fed L. sakei L-7 for 4 weeks. 16 S rRNA gene analysis indicated that intake of L. sakei L-7 increased the richness of gut microbiota and abundance of beneficial bacteria Akkermansia , Allobaculum and Parabacteroides. Metabonomics analysis revealed that beneficial metabolite gamma-aminobutyric acid and docosahexaenoic acid increased significantly. While the level of metabolite sphingosine and arachidonic acid significantly decreased. In addition, serum levels of inflammatory cytokines interleukin (IL)− 6 and tumor necrosis factor (TNF)-α were significantly decreased. The results suggested that L. sakei L-7 may promote gut health and reduce the occurrence of inflammatory response, it has the potential to become a probiotic. [Display omitted] • L. sakei L-7 showed probiotic potential in vitro evaluation. • Supplementation of L. sakei L-7 increased the abundance of beneficial bacteria in gut microbiota of mice. • L. sakei L-7 may reduce inflammation by regulating intestinal metabolism. • In vitro and in vivo studies show that L. sakei L-7 is a promising candidate strain of probiotics. [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]

Pursuing carbon neutrality has invigorated extensive investigations into sustainable and cost‐effective power sources. Iron‐air batteries (IAB) have emerged as a promising option due to their high energy density, low cost, and environmental friendliness. However, conventional IABs grapple with issues such as electrode passivation, low round‐trip energy efficiency, and parasitic hydrogen evolution. This study introduces a redox‐mediated iron‐air fuel cell (RM‐IAFC) to surmount these limitations. The RM‐IAFC employs a pair of redox mediators, respectively, in anolyte and catholyte tanks, enabling the iron oxidation and oxygen reduction reaction processes to be liberated from the electrodes. This configuration decouples energy storage and power generation, allowing fast refueling and offering operation flexibility and scalability while eliminating the need for expensive catalysts. With these salient features, the RM‐IAFC paves the way for sustainable and scalable power generation, particularly for stationary applications. [ABSTRACT FROM AUTHOR]

In this assay, a tunable pH sensing system was developed based on Ag nanoclusters (Ag NCs) capped by hyperbranched polyethyleneimine (PEI) with different molecular weights (abbreviated as Ag NC-PEIs). For instance, when the molecular weight of PEI was 600 or 1800, the fluorescence intensities of Ag NCs exhibited a linear fashion over the pH range 4.10–7.96; when the molecular weight of PEI was 25,000, the pH linear range was from 4.78 to 7.96; when the molecular weight of PEI was 70,000, the pH linear range was 6.09–8.95. According to the molecular weight of PEI 600/1800, 25,000, and 70,000, the color change point was pH 4.10–4.78, 5.33–6.09, and 6.09–6.80, respectively. Therefore, Ag NC-PEI 600 and 1800 were proper to acid conditions; Ag NC-PEI 25,000 was sensitive to weak acid media; while Ag NC-PEI 70,000 was adapted to neutral solution. The tunable and selective color change points brought an excellent feature of Ag NC-PEIs as visual pH indicators, which was flexible and applicable to a variety of environments. Besides, the ratios of absorbance at 415 nm and 268 nm of Ag NCs also showed linear relationships with pH variations. Therefore, there were three ways of this system for sensing pH values, including fluorescence assay, ultraviolet–visible measurement, and visual detection, suggesting that this tunable pH-sensing platform was more feasible, reliable, and accurate. [ABSTRACT FROM AUTHOR]

Background: The cone-rod homeobox (CRX) gene plays an important role in photoreceptor development. Recently, mutant alleles of the CRX gene have been associated with autosomal dominant Leber congenital amaurosis (LCA) and cone-rod dystrophy. The purpose of this study was to analyze the CRX mutations in a cohort of Chinese patients with LCA or early-onset severe retinal dystrophy (EOSRD) and to provide the clinical features of these patients. Methods: Patients with LCA or EOSRD were enrolled from 2003 to 2012. Detailed ocular examinations including optical coherence tomography (OCT) and standardized electrophysiology were performed. Genomic DNA was isolated with standard methods of genetic diagnosis. All three exons of CRX were amplified with PCR and screened for mutations through direct DNA sequencing. A total of 200 unrelated healthy Chinese subjects were screened to exclude nonpathogenic polymorphisms. Offspring-parent relationship was tested to confirm de novo mutation. Results: A total of 109 probands from 109 unrelated families were selected for mutation screening of the CRX gene. Two individuals with LCA were confirmed to carry de novo CRX mutations c.421delT (p.Ser141Pro fsX46) and c.571delT (p.Tyr191Met fsX3), respectively. The daughter of Case 1 also carried the same CRX mutation (c.421delT) and had LCA symptoms. Pigmentary retinopathy in the peripheral retina and macular atrophy were observed in the two probands. Macular atrophy without normal lamination structure was the retina phenotype under OCT. Conclusions: Two de novo mutations in CRX were found in Chinese patients with LCA. The CRX mutation might create a dominantly inherited trait. [ABSTRACT FROM AUTHOR]

Aims: Punicalagin (PU) is one of the major ellagitannins found in the pomegranate ( Punica granatum), which is a popular fruit with several health benefits. So far, no studies have evaluated the effects of PU on nonalcoholic fatty liver disease (NAFLD). Our work aims at studying the effect of PU-enriched pomegranate extract (PE) on high fat diet (HFD)-induced NAFLD. Results: PE administration at a dosage of 150 mg/kg/day significantly inhibited HFD-induced hyperlipidemia and hepatic lipid deposition. As major contributors to NAFLD, increased expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukins 1, 4, and 6 as well as augmented oxidative stress in hepatocytes followed by nuclear factor (erythroid-derived-2)-like 2 (Nrf2) activation were normalized through PE supplementation. In addition, PE treatment reduced uncoupling protein 2 (UCP2) expression, restored ATP content, suppressed mitochondrial protein oxidation, and improved mitochondrial complex activity in the liver. In contrast, mitochondrial content was not affected despite increased peroxisomal proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and elevated expression of genes related to mitochondrial beta-oxidation after PE treatment. Finally, PU was identified as the predominant active component of PE with regard to the lowering of triglyceride and cholesterol content in HepG2 cells, and both PU- and PE-protected cells from palmitate induced mitochondrial dysfunction and insulin resistance. Innovation: Our work presents the beneficial effects of PE on obesity-associated NAFLD and multiple risk factors. PU was proposed to be the major active component. Conclusions: By promoting mitochondrial function, eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of NAFLD. Antioxid. Redox Signal. 21, 1557-1570. [ABSTRACT FROM AUTHOR]

Abstract: Adipogenesis and lipid accumulation during aging have a great impact on the aging process and the pathogenesis of chronic, age-related diseases. However, little is known about the age-related molecular changes in lipid accumulation and the mechanisms underlying them. Here, using 5-month- and 25-month-old rats (young and old, respectively), we found that epididymal fat is the only tissue to accumulate during aging. By testing tissues rich with mitochondria in old and young animals, we found that the old animals had elevated levels of triglycerides in their muscle, heart and liver tissues but not in their kidneys, while, the mRNA level of fatty acid synthase remained unchanged among the four tissues. Regarding lipid catabolism, we determined that the activities of mitochondrial ETC. complexes changed in aged rats (muscle: decreased complex I and V activities; heart: decreased complex I activity; liver: increased complex I and III activities; kidney: decreased complex I and increased complex II activities), while changes in mitochondrial content were not observed in the muscle, heart nor in the liver tissue except increased complex IV and V subunits in aged kidneys. Furthermore, decreased mitochondrial fusion marker Mfn2 and decreased PGC-1α level were observed in the aged muscle, heart and liver but remained unchanged in the kidneys. Down-regulation of Mfn2 with siRNA in 293T cells induced significant mitochondrial dysfunction including decreased oxygen consumption, decreased ATP production, and increased ROS production, followed by increased triglyceride content suggesting a contributing role of decreased mitochondrial fusion to lipid deposit. Meanwhile, judging from autophagy marker p62/SQSTM1 and LC3-II, autophagy was suppressed in the aged muscle, heart and liver but remained unchanged in the kidneys. Taken together, these data suggest that reduction in PGC-1α expression and disruption of mitochondrial dynamics and autophagy might contribute to lipid accumulation during aging. [Copyright &y& Elsevier]

The electrical double layer (EDL) plays an essential role in the microfabric development and macroscale mechanical behaviors of clayey soils. However, how salt concentration and cation valence affect the shearing behaviors of EDL at nanoscale is still unclear. Through molecular dynamics (MD) simulations, this study systematically investigated the microstructure and the shearing properties of the kaolinite-water-salt system. During the shearing process, ions showed two kinds of movement patterns, including the restricted movement pattern and the free movement pattern. In addition, the fluidity of the strongly bound water on gibbsite surfaces, the strongly bound water on siloxane surfaces, the weakly bound water and the bulk water decreased gradually. Furthermore, with the increase of salt concentration and cation valence, some water molecules in the diffusion layer escaped into the bulk water, which finally resulted in a compression of the EDL and a decrease of the solution viscosity. By measuring the displacement of water molecules around clay platelets, the essence of the EDL compression was verified and explained for the first time. The simulation results offered a microscopic insight into the shearing behaviors of clay-water-salt systems and would promote further investigations of clay-water-salt interactions under various environments. [Display omitted] • Ions around clay platelets showed restricted and free movement patterns during shearing. • Four kinds of trajectories with distinct characteristics for water molecules were observed during shearing. • Increasing salt concentration and cation valence caused diffusion layer water molecules moved into bulk water. • Compression of the diffusion water layer decreased the viscosity of pore salt solutions. [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]

Abstract: Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5μM, which was much more efficient than curcumin. Both 0.5μM C3 and 5μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. [Copyright &y& Elsevier]

Abstract: The familial transthyretin (TTR) amyloidosis (FTA) demonstrates variable penetrance of clinical features associated with mutations in the plasma thyroid hormone-binding protein TTR gene. The purpose of this study was to assess the ocular features, to analyze vitreous and serum vascular endothelial growth factor (VEGF) levels, and to identify the genetic defect in a Chinese family with TTR FTA. The pedigree of interest was a three-generation family with eleven members. The primary ocular signs were vitreous opacities, beginning from the third or fourth decade, accompanied by retinal vasculitis, hemorrhages, and widespread pinpoint deposits in the peripheral retina. Two patients underwent vitrectomy with marked improvement of visual acuity postoperatively. Vitreous and serum samples for VEGF were analyzed with an enzyme-linked immunosorbent assay (ELISA). Forty-eight healthy adult volunteers were enrolled as a control group for the analysis of serum VEGF. Eight subjects who underwent vitrectomy for a macular epiretinal membrane or macular hole were enrolled as control for the analysis of vitreous VEGF. Both serum and vitreous VEGF levels of patients were raised compared to that of controls. Venous blood was collected from family members and the genomic DNA was extracted. All exons and exon–intron boundaries of the TTR gene were sequenced. A previously-described pathogenic transversion in exon 2 (c.G106C, p.Ala36Pro) was identified. Within this family eight individuals were confirmed as affected. In conclusion, a Chinese family with TTR Ala36Pro associated FTA is characterized by early ocular involvement. Widespread pinpoint lesions indicate RPE lesions caused by TTR deposition. FTA is associated with increased VEGF levels, both in serum and vitreous. [Copyright &y& Elsevier]

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: The Nrf2-Keap1 pathway is believed to be a critical regulator of the phase II defense system against oxidative stress. By activation of Nrf2, cytoprotective genes such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase (NQO-1) and γ-glutamyl-cysteine ligase (GCL) are induced. GCL-induced glutathione (GSH) production is believed to affect redox signaling, cell proliferation and death. We here report that tert-butyl hydroperoxide (t-BHP)-induced GSH reduction led to mitochondrial membrane potential loss and apoptosis in cultured human retinal pigment epithelial cells from the ARPE-19 cell line. Hydroxytyrosol (HT), a natural phytochemical from olive leaves and oil, was found to induce phase II enzymes and GSH, thus protect t-BHP-induced mitochondrial dysfunction and apoptosis. Depletion of GSH by buthionine-[S,R]-sulfoximine enhanced t-BHP toxicity and abolished HT protection. Overexpression of Nrf2 increased GSH content and efficiently protected t-BHP-induced mitochondrial membrane potential loss. Meanwhile, HT-induced GSH enhancement and induction of Nrf2 target gene (GCLc, GCLm, HO-1, NQO-1) messenger RNA (mRNA) were inhibited by Nrf2 knockdown, suggesting that HT increases GSH through Nrf2 activation. In addition, we found that HT was able to activate the PI3/Akt and mTOR/p70S6-kinase pathways, both of which contribute to survival signaling in stressed cells. However, the effect of HT was not inhibited by the PI3K inhibitor LY294002. Rather, c-Jun N-terminal kinase (JNK) activation was found to induce p62/SQSTM1 expression, which is involved in Nrf2 activation. Our study demonstrates that Nrf2 activation induced by the JNK pathway plays an essential role in the mechanism behind HT''s strengthening of the antiapoptotic actions of the endogenous antioxidant system. [Copyright &y& Elsevier]

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]

To compare disease severity in detail between patients carrying variants in exons 1–14 and ORF15 of retinitis pigmentosa GTPase regulator (RPGR). Systematic next-generation sequencing data analysis, Sanger sequencing validation and segregation analysis were utilised to identify the pathogenic variants. Detailed ophthalmic examinations, including electroretinograms, fundus photography, fundus autofluorescence and optical coherence tomography were performed. Statistical analysis, including age adjustment and comparison, were performed based on cross-sectional level to compare disease severity between variants in the two RPGR variant groups. Sixty-two variants were identified in RPGR in 86 patients from 77 unrelated families. Twenty-nine (37.7%) had variants in RPGR -exons 1–14 (group 1) and 48 (62.3%) in RPGR -ORF15 (group 2). Eighty-four patients were diagnosed with X-linked retinitis pigmentosa and only two patients with cone-rod dystrophy. LogMAR visual acuity increased 0.035 and 0.022 each year on average in group 1 and group 2, respectively. Group 2 patients had better visual acuity with a mean logMAR difference of 0.4378, which is significant after age adjustment (P < 0.01). Neither the value of log (ellipsoid zone width) nor central retinal thickness was significantly correlated with variant grouping after considering the effect of the age variable (P = 0.56 and 0.40, respectively). Spherical refractive error did not differ significantly between the two variant groups (P = 0.17). Patterns of autofluorescence included a hyperfluorescent ring at the posterior pole, diffuse hyperfluorescence in the macular area, and dark macular autofluorescence with or without fovea hyperfluorescence. The age and proportion of fundus autofluorescence patterns between the two variant groups were significantly different (P < 0.01). Patients with variants in exons 1–14 retained less visual acuity than patients with ORF15 variants and deteriorated faster. However, the ellipsoid zone widths, central retinal thickness and refractions were comparable between the two groups. Autofluorescence pattern relates to the age and the variant grouping. • The paper described phenotypic variability in a large cohort of 86 Chinese patients from 77 unrelated families with mutations in RPGR gene. • We focused on comparing disease severity between variants in two predominant retinal RPGR isoforms, by assessing different retina function parameters in detail. • At a given age, patients with variants in exons 1–14 retained less visual acuity than patients with ORF15 variants and progressed at a faster rate. • The visual fields, EZWs and refractions are comparable between the two variant groups. [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]

Ultrasonic tag tracking technology has been widely used in fish behavior research, but most existing studies obtain fish movement trajectories through use of supporting software or post-processing services provided by the manufacturers of the relevant equipment. Articles concerning fish positioning principles and optimization and processing methods suited to complex water environments, are rarely published. This paper proposes a set of solutions permitting precise capture of fish movement trajectories. The proposed methods can effectively mitigate the impact of difficult conditions such as partial loss of time synchronization signals and data containing gross error-bearing observations on the process of locating tagged fish. Test results show that: (1) Even if time synchronization signals for a continuous 2 h period are lost, the accuracy of time synchronization between the hydrophones remains consistent with the requirements of meter-level positioning. (2) The proposed method can effectively detect the existence of gross errors exceeding 10 m in the observation data; the success rate of the method in identifying unique gross error-bearing observations was 99.7%. (3) Based on existing hydrophones with millisecond-level observation precision, three-dimensional (3D) positioning of fish-borne signal tags to 2˜5 m precision is possible. [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]

A modified multipath error mitigation method using the multi-point hemispherical grid model (MHGM) is proposed, and the influence of changes in the observation environments of IGS stations on their data quality is evaluated. The multipath error models of different satellite pairs for different observation periods can be established using the integrated multi-GNSS data in the proposed method. The test under deliberate high multipath environment reveals that this method can effectively estimate the GNSS multipath error, detect and present the orientation of the interference sources around the station. The RMS of residuals and the kinematic positioning accuracy on day 237 of 2018 are improved by 68% and 61%, respectively. Compared with the empirical site model (ESM), which can also visualize the effects of the multipath, the RMS of residuals when applying the MHGM is improved by 20%. The test with IGS historical observations shows that MHGM can effectively reflect the influence of changing multipath interference around stations on carrier phase observations, with an average improvement of 25% in the RMS of carrier phase residuals in the extrapolated 9-day validations over the past 18 years. The results of a kinematic positioning experiment in 2019 generally coincide with the RMS statistic results of carrier phase residuals as well. The MHGM demonstrates distinct potential in the influence evaluation of changes for the multipath interference around the stations on their observation quality. [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]

Purpose: To investigate the clinical and genetic characteristics for a large cohort of Chinese patients with Bietti crystalline retinopathy (BCR). Methods: A total of 208 Chinese BCR patients from 175 families were recruited. Comprehensive clinical evaluations and genetic analysis were performed. Genotype-phenotype correlations were evaluated through statistical analysis. Results: The patients' median age was 37 years (range, 20–76 years). The median best corrected visual acuity (BCVA) was 0.8 LogMAR unit (range, 2.8 to −0.12). A significant decline of BCVA was revealed in patients over 40 years old (P<0.001). Two clinical types were observed: peripheral type (type P) and central type (type C). Significantly more type C patients had a worse central visual acuity, but a more preserved retinal function (P<0.05). Molecular screening detected biallelic CYP4V2 pathogenic variants in 98.3% (172/175) of the families, including 19 novel ones. The most frequent pathogenic variant was c.802-8_810del17insGC, with the allele frequency of 55.7% (195/350), followed by c.992A>C (28/350, 8%) and c.1091-2A>G (23/350, 6.6%). BCR patients with one c.802-8_810del17insGC and one truncating variant (IVS6-8/Tru) had BCVA>1.3 LogMAR unit (Snellen equivalent<20/400) at a younger age than those with homozygous c.802-8_810del17insGC variants (homo IVS6-8) (P=0.031). Conclusions: BCR patients preserved relatively good vision before 40 years old. Two distinct clinical types of BCR were observed. BCR patients with IVS6-8/Tru had an earlier decline in visual acuity than those with homo IVS6-8. Our findings enhance the knowledge of BCR and will be helpful in patient selection for gene therapy. [ABSTRACT FROM AUTHOR]