Objective. To investigate the diagnostic value of interferon-gamma release assays combined with multiple indicators for tuberculous peritonitis. Methods. Patients who were admitted to the hospital ...due to suspected tuberculous peritonitis were prospectively included during the 30-month study period. Moreover, healthy individuals were recruited and included in the control group. All the study participants were assessed using various indexes, such as interferon-gamma release assays. Results. A total of 180 patients with suspected tuberculous peritonitis were enrolled, and 24 were excluded. 73 patients with a confirmed diagnosis of tuberculous peritonitis were included in the tuberculous peritonitis group, 83 patients with other diseases in the other-disease control group, and 52 healthy individuals in the control group. Moreover, 83 patients in the other-disease control group and 52 participants in the control group were identified as 135 nontuberculous peritonitis patients. The area under the receiver operating characteristics curve for the QuantiFERON-TB test was 0.851 (95% confidence interval: 0.799–0.903), and the optimal cutoff value was 0.55 IU/mL, which corresponds to a sensitivity and specificity of 86.30% and 80.00%, respectively. The receiver operating characteristic curves for the combination of the QuantiFERON-TB test and the use of erythrocyte sedimentation rate, serum adenosine deaminase level, serum cancer antigen 125 level, and hypersensitive C-reactive protein level had an area under the curve of 0.859 (95% confidence interval: 0.809–0.909), with a sensitivity and specificity of 97.26% and 62.96%, respectively. Conclusions. The combined use of the QuantiFERON-TB test and multiple indexes can significantly improve the accuracy of diagnosing tuberculous peritonitis.
Protein-polysaccharide complexes have been widely used to stabilize emulsions, but the effect of NaCl on ovalbumin-xanthan gum (OVA-XG) complex emulsions is unclear. Therefore, OVA-XG complex ...emulsions with different XG concentrations at pH 5.5 were prepared, and the effects of NaCl on them were explored. The results indicated that the NaCl significantly affected the interaction force between OVA-XG complexes. The NaCl improved the adsorption of proteins at the oil-water interface and significantly enhanced emulsion stability, and the droplet size and zeta potential of the emulsion gradually decreased with increasing NaCl concentrations (0-0.08 M). In particular, 0.08 M NaCl was added to the OVA-0.2% XG emulsion, which had a minimum droplet size of 18.3 μm. Additionally, XG as a stabilizer could improve the stability of the emulsions, and the OVA-0.3% XG emulsion also exhibited good stability, even without NaCl. This study further revealed the effects of NaCl on emulsions, which has positive implications for the application of egg white proteins in food processing.
Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing ...mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the in vitro neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.
In recent years, with the increasing awareness of consumers about the relationship between excessive fat intake and chronic diseases, such as obesity, heart disease, diabetes, etc., the demand for ...low-fat foods has increased year by year. However, a simple reduction of fat content in food will cause changes in physical and chemical properties, physiological properties, and sensory properties of food. Therefore, developing high-quality fat replacers to replace natural fats has become an emerging trend, and it is still a technical challenge to completely simulate the special function of natural fat in low-fat foods. This review aims to provide an overview of development trends of fat replacers, and the different types of fat replacers, the potential fat replacement mechanisms, sensory evaluation methods, and their consumer acceptance are discussed and compared, which may provide a theoretical guidance to produce fat replacers and develop more healthy low-fat products favored by consumers.
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•This article covers the types, mechanisms and sensory evaluation methods of fat replacers.•Potential mechanisms of fat replacement are discussed in terms of texture, flavor and caloric content.•Fat replacers are more beneficial to human health.•The development of fat replacers are the future trend.
•A novel architecture DeU-Net 2.0, including Temporal Deformable Aggregation Module (TDAM), Enhanced Deformable Attention Network (EDAN) and Probabilistic Noise Correction Module (PNCM), was proposed ...for 3D cardiac cine MRI segmentation (average Dice score > 95% on the Extended ACDC dataset).•TDAM takes in consecutive MR slices as inputs to enhance the feature quality of the target slice by an offset prediction network and a temporal deformable convolutional layer.•EDAN exploits pyramidal architecture and high flexible deformable convolutional layers for accurate and robust segmentation.•In EDAN, we also propose Multi-Scale Attention Module (MSAM) to exploit multi-scale self-similarity and capture the useful correspondences at different scales.•PNCM considers two feature vectors as the normal feature and a random variable that is drawn from a standard Gaussian distribution by a full connection layer to alleviate the impact of noisy samples.
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Automatic segmentation of cardiac magnetic resonance imaging (MRI) facilitates efficient and accurate volume measurement in clinical applications. However, due to anisotropic resolution, ambiguous borders and complicated shapes, existing methods suffer from the degradation of accuracy and robustness in cardiac MRI segmentation. In this paper, we propose an enhanced Deformable U-Net (DeU-Net) for 3D cardiac cine MRI segmentation, composed of three modules, namely Temporal Deformable Aggregation Module (TDAM), Enhanced Deformable Attention Network (EDAN), and Probabilistic Noise Correction Module (PNCM). TDAM first takes consecutive cardiac MR slices (including a target slice and its neighboring reference slices) as input, and extracts spatio-temporal information by an offset prediction network to generate fused features of the target slice. Then the fused features are also fed into EDAN that exploits several flexible deformable convolutional layers and generates clear borders of every segmentation map. A Multi-Scale Attention Module (MSAM) in EDAN is proposed to capture long range dependencies between features of different scales. Meanwhile, PNCM treats the fused features as a distribution to quantify uncertainty. Experimental results show that our DeU-Net achieves the state-of-the-art performance in terms of the commonly used evaluation metrics on the Extended ACDC dataset and competitive performance on other two datasets, validating the robustness and generalization of DeU-Net.
Understanding the degradation of pentachlorophenol (PCP) by indigenous microorganisms stimulated by an electron donor and shuttle in paddy soil, and the influences of PCP/electron donor/shuttle on ...the native microbial community are important for biodegradation and ecological and environmental safety. Previous studies focused on the kinetics and the microbial actions of PCP degradation, however, the effects of toxic and antimicrobial PCP and electron donor/shuttle on the microbial community diversity and composition in paddy soil are poorly understood. In this study, the effects of PCP, an electron donor (lactate), and the electron shuttle (anthraquinone-2, 6-disulfonate, AQDS) on the microbial community in paddy soil were investigated. The results showed that the presence of PCP reduced the microbial diversity compared to the control during PCP degradation, while increased the microbial diversity was observed in response to lactate and AQDS. The addition of PCP stimulated the microorganisms involved in PCP dechlorination, including Clostridium, Desulfitobacterium, Pandoraea, and unclassified Veillonellaceae, which were dormant in raw soil without PCP stress. In all of the treatments with PCP, the addition of lactate or AQDS enhanced PCP dechlorination by stimulating the growth of functional groups involved in PCP dechlorination and by changing the microbial community during dechlorination process. The microbial community tended to be uniform after complete PCP degradation (28 days). However, when lactate and AQDS were present simultaneously in PCP-contaminated soil, lactate acted as a carbon source or electron donor to promote the activities of microbial community, and AQDS changed the redox potential because of the production of reduced AQDS. These findings enhance our understanding of the effect of PCP and a biostimulation method for PCP biodegradation in soil ecosystems at the microbial community level, and suggest the appropriate selection of an electron donor/shuttle for accelerating the bioremediation of PCP-contaminated soils.
•PCP decreased the microbial community diversity of the paddy soil.•Dechlorinating bacteria were stimulated with the stress of PCP.•Electron donor had a greater impact on the microbial community than electron shuttle.•The microbial community tended to be uniform after PCP complete degradation.
This study was to assess the lot-to-lot consistency, immunogenicity and safety of three manufacturing lots of a quadrivalent inactivated influenza vaccine (IIV4).
A randomized, double-blind, phase IV ...clinical trial was conducted in healthy children, adolescents and adults aged 9–59 years in Guizhou Province, China. Eligible participants were enrolled and randomized into three groups in a ratio of 1:1:1 to receive a single dose of one of three manufacturing lots of IIV4. Serum samples were collected before and 28 days after vaccination for hemagglutination inhibition (HI) antibody testing. Safety data were collected for up to 28 days after vaccination. The primary objective was to evaluate the lot-to-lot consistency of immune response as assessed by the geometric mean titer (GMT) of HI antibody at 28 days after vaccination.
Between November 27, 2022 and December 18, 2022, 1260 eligible participants were enrolled, with similar participant demographics among groups. Immune responses after vaccination were comparable across groups, with the 95% confidence intervals (CIs) of GMT ratios for all 4 strains falling into the equivalence criterion of (0.67, 1.5). The seroconversion rates (SCRs) and seroprotection rates (SPRs) met the US Center or Biologics Evaluation and Research (CBER) criteria for all strains for each lot (lower limit of 95% CI of SCR ≥ 40% and SPR ≥ 70%). The incidences of solicited and unsolicited adverse reactions were similar among three groups, most of which (91.9%) were mild or moderate in severity. A total of 11 serious adverse events were reported during the study, and all were considered unrelated to vaccination.
The three manufacturing lots of IIV4 demonstrated consistent immunogenicity. IIV4 can elicit satisfactory immune responses for all four strains and no safety concerns were identified.
Clinical trial registration: Identifier No. NCT05512494.
•The first lot-to-lot consistency study to demonstrate the stability of manufacturing process.•The first study to prove that IIV4 has good immunogenicity and safety in multi-ethnic population, such as Dong and Miao, other than Han in China.•IIV4 could induce good immune response in both adolescents and adults.•Vaccination with IIV4 did not increase additional safety risk.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder associated with both genetic and environmental risks. Neuroimaging approaches have been widely employed to parse the ...neurophysiological mechanisms underlying ASD, and provide critical insights into the anatomical, functional, and neurochemical changes. We reviewed recent advances in neuroimaging studies that focused on ASD by using magnetic resonance imaging (MRI), positron emission tomography (PET), or single-positron emission tomography (SPECT). Longitudinal structural MRI has delineated an abnormal developmental trajectory of ASD that is associated with cascading neurobiological processes, and functional MRI has pointed to disrupted functional neural networks. Meanwhile, PET and SPECT imaging have revealed that metabolic and neurotransmitter abnormalities may contribute to shaping the aberrant neural circuits of ASD. Future large-scale, multi-center, multimodal investigations are essential to elucidate the neurophysiological underpinnings of ASD, and facilitate the development of novel diagnostic biomarkers and better-targeted therapy.
•Increased crash rates are associated with indicators of poor “safety culture”.•A relationship between crashes and violations such as “unsecured fire extinguisher” exists, relating to safety ...culture.•Crashes are rare; improved prediction comes from resampling the data to increase the ratio of crashes to non-crashes.•The authors recommend increased training and support for drivers to reduce roadway crashes and improve safety culture.
Many researchers have developed predictive models of crashes based on the safety scores of commercial truck companies, but these studies have been based on aggregated data at the truck company level—evaluating the total crashes and violations per company over a period of time. This level of aggregation obscures critical information. Here, a new approach to organizing non-aggregated data is taken, and logistic regression and random forest models are applied to non-aggregated FMCSA roadside inspection, violation, and crash data at the specific vehicle level. Resampling methods are used to improve model performance where there are relatively few events of interest—crashes. These results point not to specific “unsafe” drivers, but rather, patterns of unsafe behaviors or conditions that predict roadway crashes. Working toward reducing these behaviors systematically could save lives on US highways.
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Background: With the emergence of immunotherapy in recent years, therapeutic antibodies against programmed death 1 (PD1) and its ligand (PDL1) have proven to be a huge success in ...multiple cancer types. However, these robust responses only occur in a subset of patients. Identifying mechanisms of responses and resistance is key to improve outcomes and setup new treatment strategies. Transforming Growth Factor-beta (TGF-beta) is an immunosuppressive cytokine and overexpression of TGF-beta in the tumor microenvironment is proven to be a key element of resistance to anti-tumor response. We have developed a novel peptide HTPEP-001 which blocks TGF-beta signaling in both cellular and fibrosis animal models (ATS-2020 abstract). In this study, we explored the antitumor effect and mechanism of HTPEP-001 when administered together with anti-PD1 antibody in mice models. Methods: Animal models: 1. C57BL/6 mice were inoculated subcutaneously with 5*10
5
MC38 cells. 2. BALB/c mice were inoculated on the right mammary fat pad with 1*10
5
EMT-6 cells. Treatment groups: A. HTPEP-001 (60 mg/kg, intravenously, qd); B. isotype IgG; C. rat anti-mouse PD1 (10 mg/kg, intraperitoneally, twice a week); D. Coadminstration of HTPEP-001 and anti-PD1 (combo). Treatments were initiated 4-5 days after inoculation and lasted for 10 days. ELISA, immunofluorescence and flow cytometry analysis of dissected tumors were performed. Results: Compared to anti-PD1 group, mice treated with both HTPEP-001 and anti-PD1 exhibited additional reductions in tumor size and 13% higher inhibition of tumor growth (59% in Anti-PD-1 vs 72% in combo) in MC38 model. In the EMT6 model, coadministration of HTPEP-001 and anti-PD1 also showed additional reduction in tumor burdens. Coadmistration of HTPEPE-001 and anti-PD-1 significantly decreased active TGF-beta
1
and phosphorylated Smads expression in tumors in both MC38 and EMT6 models. Furthermore, immunofluorescence and flow cytometry analysis of CD8
+
lymphocytes in tumor mass revealed markedly elevated number of cytotoxic tumor infiltrating lymphocytes in combo group compared to HTPEP-001 and anti-PD1 groups. Conclusions: This study showed that HTPEP-001 enhanced the anti-tumor activity of anti-PD1 via suppressing TGF-beta signaling and promoting infiltration of cytotoxic lymphocytes in two syngeneic tumor models. We will continue to develop HTPEP-001 as an add-on therapy to checkpoint inhibitors with a goal to improve the outcomes of current immunotherapy.
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