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Abstract Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.

To mitigate the continued impact of SARS-CoV-2, influenza A, and influenza B viruses on human health, a smartphone-based point-of-care testing (POCT) system was designed to detect respiratory pathogens through a nucleic acid test. This compact, light-weight, highly automated, and universal system enables the differential diagnosis of SARS-CoV-2, influenza A, and influenza B in approximately 30 min in a single-tube reaction. Numerous hospitals and disease control and prevention center assessed the triple POCT system’s detection threshold, sensitivity, specificity, and stability, and have concluded that all the assessments were comparable to those of fluorescent quantitative polymerase chain reaction (PCR)-based testing. The triple POCT system is suitable as an onsite rapid-diagnosis device, as well as for pathogen screening at airports and customs.

ABSTRACTSalmonella enterica is a prominent cause of foodborne disease in the United States. However, the mechanism and route of pathogen transmission that leads to Salmonella infection in commercial processing plants are poorly understood. This study aimed to investigate the effect of mixed-species biofilms on S. enterica survival and persistence under sanitizer stress [Quaternary ammonium compounds (QACs)] by analyzing 78 floor drain samples from a meat processing facility and three S. enterica strains (serovars Cerro, Montevideo, and Typhimurium) isolated from that facility and an unrelated source. The four test groups were as follows: control, QAC treatment, Salmonella addition, and QAC treatment with Salmonella addition. DNAs were extracted, and 16S rRNA gene based on the variable region V4 amplicon sequencing was performed to analyze the relative abundance, core microbiome, and Alpha and Beta diversity using the qiime2 pipeline. At the genus level, the Brochothrix (45.56%), Pseudomonas (38.94%), Carnobacterium (6.18%), Lactococcus (4.68%), Serratia (3.14%), and Staphylococcus (0.82%) were shown to be the most prevalent in all drain samples. The results demonstrate that the relative abundance of different bacterial genera was affected by both QAC treatment and Salmonella addition, with some genera showing increases or decreases in abundance. Notably, the correlation network was constructed to understand the relationships between the different bacteria. Nitrospira had the greatest number of connections in the floor drain environment network, with two negative and eight positive correlations. The results suggest that Nitrospira in the mixed-species biofilm community may play a role in converting ammonium in the QAC sanitizer into nitrites. Thus, Nitrospira could be a potentially important genus in providing sanitizer resistance to pathogen-encompassed mixed-species biofilms.IMPORTANCESalmonella contamination in meat processing facilities can lead to foodborne illness outbreaks. Our study characterized the microbiome dynamics in beef facility drains and their response to Salmonella addition and common sanitizer (QAC). Nitrospira could be an important genus in providing sanitizer resistance to pathogen-encompassed mixed-species biofilms. The results provide insight into the impact of mixed-species biofilms on Salmonella survival and persistence under sanitizer stress in meat processing facilities. The results highlight the need to consider mixed-species biofilm effects when developing targeted interventions to enhance food safety.

Abstract This study developed a new tool, differential staining fluorescence microscopy (DSFM), to measure the biovolume and track the location of enteric pathogens in mixed-species biofilms which can pose a risk to food safety in beef processing facilities. DSFM was employed to examine the impact of pathogenic bacteria, Escherichia coli O157:H7 and three different Salmonella enterica strains on mixed-species biofilms of beef processing facilities. Fourteen floor drain biofilm samples from three beef processing plants were incubated with overnight BacLight stained enteric pathogens at 7 °C for 5 days on stainless steel surface then counter-stained with FM-1-43 biofilm stain and analyzed using fluorescence microscopy. Notable variations in biovolume of biofilms were observed across the fourteen samples. The introduction of E. coli O157:H7 and S. enterica strains resulted in diverse alterations of biofilm biovolume, suggesting distinct impacts on mixed-species biofilms by different enteric pathogens which were revealed to be located in the upper layer of the mixed-species biofilms. Pathogen strain growth curve comparisons and verification of BacLight Red Stain staining effectiveness were validated. The findings of this study show that the DSFM method is a promising approach to studying the location of enteric pathogens within mixed-species biofilms recovered from processing facilities. Understanding how foodborne pathogens interact with biofilms will allow for improved targeted antimicrobial interventions.

The soil in a lead–zinc mining area, contaminated with heavy metals like cadmium (Cd) and lead (Pb), poses a risk to crops such as maize. Experiments using biochar and sepiolite as soil ameliorants in potted maize showed these substances can mitigate heavy metal contamination. Biochar increased potassium and phosphorus in the soil and maize, while sepiolite significantly boosted overground phosphorus by 73.2%. Both ameliorants transformed Cd and Pb into a more stable state in the soil, reducing their accumulation in maize, especially with biochar, which effectively inhibited metal migration during leaching events. This study provided insights for further improvement of soil amendments and multi-factor application experiments.

Rheumatoid arthritis (RA) is a common chronic inflammatory disease characterized by the proliferation of fibroblast-like synoviocytes (FLS), pannus development, cartilage, and bone degradation, and, eventually, loss of joint function. Fibroblast activating protein (FAP) is a particular product of activated FLS and is highly prevalent in RA-derived fibroblast-like synoviocytes (RA-FLS). In this study, zinc ferrite nanoparticles (ZF-NPs) were engineered to target FAP+ (FAP positive) FLS. ZF-NPswere discovered to better target FAP+ FLS due to the surface alteration of FAP peptide and to enhance RA-FLS apoptosis by activating the endoplasmic reticulum stress (ERS) system via the PERK-ATF4-CHOP, IRE1-XBP1 pathway, and mitochondrial damage of RA-FLS. Treatment with ZF-NPs under the influence of an alternating magnetic field (AMF) can significantly amplify ERS and mitochondrial damage via the magnetocaloric effect. It was also observed in adjuvant-induced arthritis (AIA) mice that FAP-targeted ZF-NPs (FAP-ZF-NPs) could significantly suppress synovitis in vivo, inhibit synovial tissue angiogenesis, protect articular cartilage, and reduce M1 macrophage infiltration in synovium in AIA mice. Furthermore, treatment of AIA mice with FAP-ZF-NPs was found to be more promising in the presence of an AMF. These findings demonstrate the potential utility of FAP-ZF-NPs in the treatment of RA.

Salmonella entericais a leading cause of foodborne illness in the United States. In this study, 3S. enterica strains (serovars Cerro, Montevideo, and Typhimurium) were isolated from a beef processing plant with a history of Salmonella recurrence. Floor drains of the hotbox area and storage cooler of the same plant were sampled for environmental microorganisms. Biofilm formation on stainless steel (SS) by the microorganisms recovered from the drains and surface colonization by the isolated S. enterica strains were assessed. Pathogen survival and community compositions after sanitization (quaternary ammonium compound [QAC]) were examined. Alone the Cerro strain exhibited greater (P

Hyperspectral unmixing, which decomposes mixed pixels into the endmembers and corresponding abundances, is an important image process for the further application of hyperspectral images (HSIs). Lately, the unmixing problem has been solved using deep learning techniques, particularly autoencoders (AEs). However, the majority of them are based on the simple linear mixing model (LMM), which disregards the spectral variability of endmembers in different pixels. In this article, we present a multi-attention AE network (MAAENet) based on the extended LMM to address the issue of the spectral variability problem in real scenes. Moreover, the majority of AE networks ignore the global spatial information in HSIs and operate pixel- or patch-wise. We employ attention mechanisms to design a spatial–spectral attention (SSA) module that can deal with the band redundancy in HSIs and extract global spatial features through spectral correlation. Moreover, noticing that the mixed pixels are always present in the intersection of different materials, a novel sparse constraint based on spatial homogeneity is designed to constrain the abundance and abstract local spatial features. Ablation experiments are conducted to verify the effectiveness of the proposed AE structure, SSA module, and sparse constraint. The proposed method is compared with several state-of-the-art unmixing methods and exhibits competitiveness on both synthetic and real datasets.

BackgroundPrevious studies have shown that the all-cause mortality and non-colorectal cancer mortality of patients with fecal occult blood test (FOBT) positivity are significantly increased, implying that FOBT results may have more prognostic value.MethodsRetrospective analysis was performed for gastric cancer (GC) patients who underwent R0 gastrectomy from July 2007 to July 2014 at our hospital. Propensity score matching (PSM) was used to reduce confounding bias and a computerized technique for the nearest available score matching without replacement was applied. The cumulative survival rate was calculated using the Kaplan-Meier method and a log-rank test. Cox proportional hazards regression and logistic regression was used to determine the independent prognostic factors associated with survival and postoperative complications, respectively. The expression level of tumor-associated macrophages (TAMs) and proinflammatory cytokines (TNF-α, IL-6) were evaluated by immunohistochemical (IHC).ResultsA total of 3,003 patients were included and 246 patients (8.2%) were in preoperative FOBT positive status. There was no significant difference in demographic data between preoperative FOBT positive and negative group after a 1:4 PSM. The overall postoperative complications, major complications, and anastomotic leakage were significantly higher in the preoperative FOBT-positive group than in the preoperative FOBT-negative group. Moreover, preoperative FOBT-positivity was an independent risk factor for 5-year overall survival (OS) (HR: 1.32, p = 0.005). For stage II/III patients, the postoperative adjuvant chemotherapy (PAC) benefit was found in preoperative FOBT-negative group (5-year OS: 49.9 vs. 36.8%, p = 0.001), whereas the PAC benefit was lost in preoperative FOBT-positive groups (5-year OS: 40.8 vs. 37.7% p = 0.896). Finally, IHC found that preoperative FOBT-positivity in patients was significantly associated with higher TAMs infiltration and higher expression of IL-6 and TNF-α in tumor tissues than in the preoperative FOBT-negative group.ConclusionAs a simple and low-cost method, preoperative FOBT results can predict both complications and survival after R0 gastrectomy for GC. More importantly, stage II/III GC patients with FOBT-positive seem not benefit from PAC alone. Further exploration is warranted.

RNA polymerase III (Pol III) products play essential roles in ribosome assembly, protein synthesis, and cell survival. Deregulation of Pol-III-directed transcription is closely associated with tumorigenesis. However, the regulatory pathways or factors controlling Pol-III-directed transcription remain to be investigated. In this study, we identified a novel role of EGR1 in Pol-III-directed transcription. We found that Filamin A (FLNA) silencing stimulated EGR1 expression at both RNA and protein levels. EGR1 expression positively correlated with Pol III product levels and cell proliferation activity. Mechanistically, EGR1 downregulation dampened the occupancies of Pol III transcription machinery factors at the loci of Pol III target genes. Alteration of EGR1 expression did not affect the expression of p53, c-MYC, and Pol III general transcription factors. Instead, EGR1 activated RhoA expression and inhibited PTEN expression in several transformed cell lines. We found that PTEN silencing, rather than RhoA overexpression, could reverse the inhibition of Pol-III-dependent transcription and cell proliferation caused by EGR1 downregulation. EGR1 could positively regulate AKT phosphorylation levels and is required for the inhibition of Pol-III-directed transcription mediated by FLNA. The findings from this study indicate that EGR1 can promote Pol-III-directed transcription and cell proliferation by controlling the PTEN/AKT signalling pathway.

In this paper, we study the statistical inference of the generalized inverted exponential distribution with the same scale parameter and various shape parameters based on joint progressively type-II censored data. The expectation maximization (EM) algorithm is applied to calculate the maximum likelihood estimates (MLEs) of the parameters. We obtain the observed information matrix based on the missing value principle. Interval estimations are computed by the bootstrap method. We provide Bayesian inference for the informative prior and the non-informative prior. The importance sampling technique is performed to derive the Bayesian estimates and credible intervals under the squared error loss function and the linex loss function, respectively. Eventually, we conduct the Monte Carlo simulation and real data analysis. Moreover, we consider the parameters that have order restrictions and provide the maximum likelihood estimates and Bayesian inference.

The present study introduced a modified delta-shaped gastroduodenostomy (DSG) technique and assessed the safety, feasibility and clinical results of this procedure in patients undergoing totally laparoscopic distal gastrectomy (TLDG) for gastric cancer (GC).A total of 102 patients with distal GC undergoing TLDG with modified DSG between January 2013 and December 2013 were enrolled. A retrospective study was performed using a prospectively maintained comprehensive database to evaluate the results of the procedure. Univariate and multivariate analyses were performed to estimate the predictive factors for postoperative morbidity.The mean operation time was 150.6±30.2 min, the mean anastomosis time was 12.2±4.2 min, the mean blood loss was 48.2±33.2 ml, and the mean times to first flatus, fluid diet, soft diet and postoperative hospital stay were 3.8±1.3 days, 5.0±1.0 days, 7.4±2.1 days and 12.0±6.5 days, respectively. Two patients with minor anastomotic leakage after surgery were managed conservatively; no patient experienced any complications around the anastomosis, such as anastomotic stricture or anastomotic hemorrhage. Univariate analysis showed that age, gastric cancer with hemorrhage and cardiovascular disease combined were significant factors that affected postoperative morbidity (P

The aim of this work was to demonstrate the feasibility of nisin and lactic acid production from corn stover through simultaneous saccharification and fermentation using Lactococcus lactis subsp. lactis ATCC 11454. The optimum conditions for nisin and lactic acid production were cellulose concentration of 30 g/L, a cellulase loading of 25 FPU/g cellulose and an initial pH of 6.0 in a 10 g/L yeast extract and 10 g/L peptone broth. The optimized bioprocess achieved nisin titer of 1635 IU/mL and lactic acid concentration of 15.2 g/L. The results indicated that simultaneous saccharification and fermentation with corn stover is a promising bioprocess for the economic production of nisin and lactic acid simultaneously.