Yeast ß-glucan promotes antiviral type I interferon response via dectin-1.

Pseudorabies virus (PRV), an alphaherpesvirus, is a neglected zoonotic pathogen. Dectin-1 sensing of ß-glucan (BG) induces trained immunity, which can possibly form a new strategy for the prevention of viral infection. However, alphaherpesvirus including PRV have received little to no investigation in the context of trained immunity. Here, we found that BG pretreatment improved the survival rate, weight loss outcomes, alleviated histological injury and decreased PRV copy number of tissues in PRV-infected mice. Type I interferons (IFNs) including IFN-α/ß levels in serum were significantly increased by BG. However, these effects were abrogated in the presence of Dectin-1 antagonist. Dectin-1-mediated effect of BG was also confirmed in porcine and murine macrophages. These results suggested that BG have effects on type I IFNs with antiviral property involved in Dectin-1. In piglets, oral or injected immunization with BG and PRV vaccine could significantly elevated the level of PRV-specific IgG and type I IFNs. And it also increased the antibody levels of porcine reproductive and respiratory syndrome virus vaccine and classical swine fever vaccine that were later immunized, indicating a broad-spectrum effect on improving vaccine immunity. On the premise that the cost was greatly reducing, the immunological effect of oral was better than injection administration. Our findings highlighted that BG induced type I IFNs related antiviral effect against PRV involved in Dectin-1 and potential application value as a feed additive to help control the spread of PRV and future emerging viruses.

Hepatocellular carcinoma immune prognosis score predicts the clinical outcomes of hepatocellular carcinoma patients receiving immune checkpoint inhibitors.

OBJECTIVE: The predictive biomarkers of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) still need to be further explored. This study aims to establish a new immune prognosis biomarker to predict the clinical outcomes of hepatocellular carcinoma patients receiving immune checkpoint inhibitors. METHODS: The subjects of this study were 151 HCC patients receiving ICIs at Harbin Medical University Cancer Hospital from January 2018 to December 2021. This study collected a wide range of blood parameters from patients before treatment and used Cox's regression analysis to identify independent prognostic factors in blood parameters, as well as their ß coefficient. The hepatocellular carcinoma immune prognosis score (HCIPS) was established through Lasso regression analysis and COX multivariate analysis. The cut-off value of HCIPS was calculated from the receiver operating characteristic (ROC) curve. Finally, the prognostic value of HCIPS was validated through survival analysis, stratified analyses, and nomograms. RESULTS: HCIPS was composed of albumin (ALB) and thrombin time (TT), with a cut-off value of 0.64. There were 56 patients with HCIPS < 0.64 and 95 patients with HCIPS ≥ 0.64, patients with low HCIPS were significantly related to shorter progression-free survival (PFS) (13.10 months vs. 1.63 months, P < 0.001) and overall survival (OS) (14.83 months vs. 25.43 months, P < 0.001). HCIPS has also been found to be an independent prognostic factor in this study. In addition, the stratified analysis found a significant correlation between low HCIPS and shorter OS in patients with tumor size ≥ 5 cm (P of interaction = 0.032). The C-index and 95% CI of the nomograms for PFS and OS were 0.730 (0.680-0.779) and 0.758 (0.711-0.804), respectively. CONCLUSIONS: As a new score established based on HCC patients receiving ICIs, HCIPS was significantly correlated with clinical outcomes in patients with ICIs and might serve as a new biomarker to predict HCC patients who cloud benefit from ICIs.

Microplastic pollution in organic farming development cannot be ignored in China: Perspective of commercial organic fertilizer.

Commercial organic fertilizer, an essential fertilizer for developing organic farming in China, has been identified as a potentially important source of microplastics (MPs) on farmland. However, little is known about the occurrence of MPs in commercial organic fertilizers and their potential ecological risks nationwide. Here, stereoscopy and laser-infrared imaging spectrometry were used to comprehensively investigate the abundance, size, type and morphology of MPs in commercial organic fertilizers collected from mainland China, assess the ecological risks, and predict MP contamination. Commercial organic fertilizers contained many MPs (8.88 ×103 to 2.88 ×105 items/kg), especially rich in small-size MPs (<100 µm), accounting for 76.53%. The highest MP pollution load value was observed in fertilizers collected from East China. Chlorinated polyethylene, polyurethane, polyethylene and polypropylene were the dominant MPs with the shape of film and fragment, concentrated in small sizes (<100 µm). The risk index (H-index) of the MPs was used to quantify the ecological risk of the MPs in the different samples, and most of the fertilizers were at level Ⅲ with high risk. Predictably, 2.32 × 1013 - 2.81 × 1016 MPs will accumulate in orchard soils after five years of fertilization, especially in South, Southwest and East China. This study provides primary scientific data on MP pollution in commercial fertilizer and the health development of organic farming.

Prognostic value of nutritional and inflammatory markers in patients with hepatocellular carcinoma who receive immune checkpoint inhibitors.

The emergence of immune checkpoint inhibitors (ICIs) has provided a new treatment option for patients with hepatocellular carcinoma (HCC). However, further evaluation is needed for determining biomarkers for the use of ICIs. The present study evaluated the prognostic value of certain nutritional and inflammatory markers in patients with HCC who received ICIs. In the present study, the clinical data of 151 patients with HCC who received ICIs at Harbin Medical University Cancer Hospital from January 2019 to December 2021 were collected. The blood parameters of all patients before treatment were collected to evaluate certain nutritional and inflammatory markers, including the prognostic nutrition index (PNI), nutritional risk index (NRI), geriatric NRI (GNRI), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) and advanced lung cancer inflammation index (ALI). Patients were grouped using the cut-off value calculated using receiver operating characteristic (ROC) curves, and the relationship between these biomarkers and prognosis was evaluated through survival analysis. Furthermore, the prognostic value of these biomarkers was assessed through multivariate Cox regression analysis and construction of nomograms. Finally, time-ROC curves were plotted to compare the differences in predicting prognosis between the biomarkers. In the preliminary survival analysis, all inflammatory and nutritional markers included in the present study were significantly associated with the prognosis of HCC in patients who received ICIs. Similar results were obtained in a subgroup analysis of patients with different Barcelona Clinic Liver Cancer (BCLC) stages. Multivariate Cox regression analysis demonstrated that GNRI, PNI, BCLC stage and Tumor-Node-Metastasis (TNM) stage were significantly associated with progression-free survival (PFS), whereas GNRI, BCLC stage and TNM stage were also significantly associated with overall survival (OS). Furthermore, the time-ROC curves indicated that nutritional indicators had a higher prognostic value in all indexes, especially GNRI. The C-index (95% confidence interval) of the nomograms for predicting the survival probability of patients who received ICIs were 0.801 (0.746-0.877) and 0.823 (0.761-0.898) for PFS and overall OS, respectively, which also showed high accuracy. In conclusion, the present study demonstrated that PNI, GNRI, NRI, SII, SIRI and ALI were all related to the efficacy of ICIs in HCC and could serve as non-invasive biomarkers for ICI treatment effectiveness. Moreover, compared with inflammatory markers, nutritional markers had greater predictive ability, with GNRI being the biomarker with the best prognostic value.

Analysis on EZH2: mechanism identification of related CeRNA and its immunoassay in hepatocellular carcinoma.

OBJECTIVE: To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2 and depths of various immune cell infiltration depths. The relationship between different immune checkpoints were also analyzed. METHODS: First, the expression of EZH2 in pan-cancer (18 malignancies) was analyzed with the TCGA database. Hepatocellular carcinoma (HCC) tissues of 374 cases and normal tissues of 50 cases were analyzed in terms of the differential expression, overall survival (OS) and progression-free-survival (PFS). Then, we conducted GO and KEGG enrichment analysis on target gene. We also analyzed mRNA-miRNA and MicroRNA (miRNA)- long non-coding RNA (lncRNA) correlation with starbase databse, so as to determine the potential ceRNA mechanism associated with EZH2. Finally, immunoassay and drug-sensitivity analysis of EZH2 was performed. RESULTS: Seven potential EZH2-related ceRNA pathways were screened out, namely lncRNA: Small Nucleolar RNA Host Gene 1 (SNHG1), SNHG 3, and SNHG 6-miR-101-3p-EZH2; and lncRNA: Long Intergenic Non-Protein Coding RNA 1978 (LINC01978), SNHG12, Ring Finger Protein 216 Pseudogene 1 (RNF216P1), and Coiled-coil Domain Containing 18 Antisense RNA 1 (CCDC18-AS1)-let-7c-5p-EZH2. Finally, 4 potential EZH2-related ceRNA pathways were identified through qPCR.According to immune correlation analysis, EZH2 may be positively correlated with T cells follicular helper, T cells Cluster of differentiation (CD)4 memory activated, Macrophages M0, and B cells memory (P < 0.05, cof > 0.2); while be negatively correlated with T cells CD4 + memory resting (P < 0.05, cof < -0.2). And EZH2 is positively correlated with Programmed Cell Death 1 (PDCD1) (R = 0.22), CD274 (R = 0.3) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (R = 0.23). According to drug sensitivity analysis, patients in the high expression group were more susceptible to the effects of various drugs including Sorafenib, 5-Fluorouracil, Doxorubicin, Etoposide, Paclitaxel, and Vinorelbine than those with low expression. CONCLUSION: This study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p-EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.

Clinical plasma cells-related genes to aid therapy in colon cancer.

The tumor immune microenvironment (TIME) of colon cancer (CC) has been associated with extensive immune cell infiltration (IMI). Increasing evidence demonstrated that plasma cells (PC) have an extremely important role in advance of antitumor immunity. Nonetheless, there is a lack of comprehensive analyses of PC infiltration in clinical prognosis and immunotherapy in CC. This study systematically addressed the gene expression model and clinical information of CC patients. Clinical samples were obtained from the TCGA (The Cancer Genome Atlas) databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), GSVA, and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were employed to research the potential mechanism and pathways. Immunophenoscore (IPS) was obtained to evaluate the immunotherapeutic significance of risk score. Half maximal inhibitory concentration (IC50) of chemotherapeutic medicine was predicted by employing the pRRophetic algorithm. A total of 513 CC samples (including 472 tumor samples and 41 normal samples) were collected from the TCGA-GDC database. Significant black modules and 313 candidate genes were considered PC-related genes by accessing WGCNA. Five pivotal genes were established through multiple analyses, which revealed excellent prognostic. The underlying correlation between risk score with tumor mutation burden (TMB) was further explored. In addition, the risk score was obviously correlated with various tumor immune microenvironment (TIME). Also, risk CC samples showed various signaling pathways activity and different pivotal sensitivities to administering chemotherapy. Finally, the biological roles of the CD177 gene were uncovered in CC.

Synergistic effects of biochar derived from different sources on greenhouse gas emissions and microplastics mitigation during sewage sludge composting.

This study aimed to investigate the effects of biochar derived from different sources (wheat straw, sawdust and pig manure) on greenhouse gas and microplastics (MPs) mitigation during sewage sludge composting. Compared to the control, all biochar significantly reduced the N2O by 28.91-41.23%, while having no apparent effect on CH4. Sawdust biochar and pig manure biochar significantly reduced the NH3 by 12.53-23.53%. Adding biochar decreased the global warming potential during composting, especially pig manure biochar (177.48 g/kg CO2-eq.). The concentration of MPs significantly increased in the control (43736.86 particles/kg) compared to the initial mixtures, while the addition of biochar promoted the oxidation and degradation of MPs (15896.06-23225.11 particles/kg), with sawdust biochar and manure biochar were more effective. Additionally, biochar significantly reduced the abundance of small-sized (10-100 µm) MPs compared to the control. Moreover, biochar might regulate specific microbes (e.g., Thermobifida, Bacillus and Ureibacillus) to mitigate greenhouse gas emissions and MPs degradation.

The combination of circulating IgM and geriatric nutritional risk index predicts the prognostic of hepatocellular carcinoma patients who underwent immune checkpoint inhibitors.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have shown promise in hepatocellular carcinoma (HCC) treatment. With the increasing use of ICIs in cancer treatment, identifying biomarkers that can predict the prognosis of patients receiving ICIs is of great importance. We aimed to investigate the potential of circulating immunoglobulins and the combination of Geriatric Nutritional Risk Index (GNRI) with IgM to predict prognosis in patients with HCC who received ICIs. METHODS: Clinical and pathological data were collected from 101 patients with HCC who were administered ICIs and underwent circulating immunoglobulin testing between January 2018 and December 2021. Survival analysis, Cox regression analysis, and nomogram construction were performed to evaluate the prognostic value of the indicators. RESULTS: In the preliminary survival analysis, we observed a significant correlation between patient prognosis and IgM levels. Patients with low IgM had shorter survival times. Upon combining the GNRI with IgM, patients with low GNRI and IgM levels had shorter progression-free survival (PFS) and overall survival (OS) (P < 0.001). Additionally, GNRI-IgM had the highest area under the curve (AUC) and was identified as an independent prognostic marker in this study. The C-indices of the nomograms for PFS and OS were 0.797 (0.734-0.860) and 0.827 (0.778-0.876), respectively. CONCLUSIONS: IgM was significantly associated with the prognosis of patients with HCC receiving ICIs. The combination of the GNRI with IgM provided superior prognostic value and served as an independent prognostic marker. The GNRI-IgM can be used to effectively identify patients with HCC who are responsive to ICIs.

BTF3 promotes proliferation and glycolysis in hepatocellular carcinoma by regulating GLUT1.

Hepatocellular carcinoma (HCC) is a grievous tumor with an increasing incidence worldwide. Basic transcription factor 3 (BTF3) is discovered to regulate the expression of glucose transporter 1 (GLUT1), which benefits glycolysis, a momentous signature of tumors, through transactivation of the forkhead box M1 (FOXM1) expression. BTF3 is highly expressed in HCC. However, whether BTF3 promotes GLUT1 expression through FOXM1 to modulate glycolysis in HCC remains unclear. The expression profile of BTF3 were determined by online database, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. The role and mechanism of BTF3 in the proliferation and glycolysis of HCC cells were examined by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, XF96 Extracellular Flux analyzer, spectrophotometry and western blot analysis. In addition, the direct interaction between BTF3 and FOXM1 was verified by dual-luciferase reporter and co-immunoprecipitation assays. Moreover, the role of BTF3 was also explored in a xenografted mice model. The expression of BTF3 was increased in HCC cells and tumor tissues. Knockdown of BTF3 reduced the cell viability, Edu positive cells, extracellular acidification rate (ECAR), glucose consumption and lactate production in both Huh7 and HCCLM3 cells. The expressions of FOXM1 and GLUT1 were increased in HCC tissues, which were positively correlated with the BTF3 expression. Moreover, a direct interaction existed between BTF3 and FOXM1 in HCC cells. Downregulation of BTF3 decreased the relative protein levels of FOXM1 and GLUT1, which were rescued with overexpression of FOXM1 in both cells. More importantly, overexpression of FOXM1 restored the cell viability, ECAR, glucose consumption and lactate production in both Huh7 and HCCLM3 cells transfected with siBTF3#1. Furthermore, inhibition of BTF3 decreased tumor weight and volume, and the relative level of BTF3, FOXM1, GLUT1 and Ki-67 in tumor tissues from mice xenografted with Huh7 cells. BTF3 enhanced the cell proliferation and glycolysis through FOXM1/GLUT1 axis in HCC.

Pan-cancer analysis of SYNGR2 with a focus on clinical implications and immune landscape in liver hepatocellular carcinoma.

BACKGROUND: Synaptogyrin-2 (SYNGR2), as a member of synaptogyrin gene family, is overexpressed in several types of cancer. However, the role of SYNGR2 in pan-cancer is largely unexplored. METHODS: From the TCGA and GEO databases, we obtained bulk transcriptomes, and clinical information. We examined the expression patterns, prognostic values, and diagnostic value of SYNGR2 in pan-cancer, and investigated the relationship of SYNGR2 expression with tumor mutation burden (TMB), microsatellite instability (MSI), immune infiltration, and immune checkpoint (ICP) genes. The gene set enrichment analysis (GSEA) software was used to perform pathway analysis. Besides, we built a nomogram of liver hepatocellular carcinoma patients (LIHC) and validated its prediction accuracy. RESULTS: SYNGR2 was highly expressed in most cancers. The high expression of SYNGR2 significantly reduced the overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in multiple types of cancer. Also, receiver operating characteristic (ROC) curve analysis demonstrated that SYNGR2 showed high accuracy in distinguishing cancerous tissues from normal ones. Moreover, SYNGR2 expression was correlated with TMB, MSI, immune scores, and immune cell infiltrations. We also analyzed the association of SYNGR2 with immunotherapy response in LIHC. Finally, a nomogram including SYNGR2 and pathologic T, N, M stage was built and exhibited good predictive power for the OS, DSS, and PFI of LIHC patients. CONCLUSION: Overall, SYNGR2 is a critical oncogene in various tumors. SYNGR2 participates in the carcinogenic progression, and may contribute to the immune infiltration in tumor microenvironment. Our study suggests that SYNGR2 can serve as a predictor related to prognosis in pan-cancer, especially LIHC.

Electrostatic potential difference between tumor and paratumor regulates cancer stem cell behavior and prognose tumor spread.

Tumor spread is responsible for most deaths related to cancer. Increasing the accuracy of cancer prognosis is critical to reducing the high mortality rates in cancer patients. Here, we report that the electrostatic potential difference (EPD) between tumor and its paratumor tissue is a prognostic marker for tumor spread. This finding is concluded from the patient-specific EPD values and clinical observation. The electrostatic potential values were measured on tissue cryosections from 51 patients using Kelvin probe force microscopy (KPFM). A total of ~44% (15/34) patients of Vtumor-paratumor > 0 were featured with tumor spread, whereas only ~18% (2/11) patients of Vtumor-paratumor < 0 had tumor spread. Next, we found the increased enrichment of cancer stem cells in paratumors with lower electrostatic potentials using immunofluorescence imaging, which suggested the attribution of tumor spread to the galvanotaxis of cancer stem cells (CSCs) toward lower potential. The findings were finally validated in breast and lung spheroid models composed of differentiated cancer cells and cancer stem cells at the ratio of 1:1 and embedded in Matrigel dopped with negative-, neutral- and positive-charged polymers and CSCs prefer to spread out of spheroids to lower electrostatic potential sites. This work may inspire the development of diagnostic and prognostic strategies targeting at tissue EPDs and CSCs for tumor therapy.

[Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway].

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Dietary supplementation with synbiotics improves growth performance, antioxidant status, immune function, and intestinal barrier function in broilers subjected to cyclic heat stress.

This study investigated the effects of synbiotics supplementation on growth performance, antioxidant status, immune function, and intestinal barrier function in broilers subjected to cyclic heat stress. One hundred and forty-four 22-day-old male broilers were randomly assigned to one of three treatment groups of six replicates each for a 21-day study, with eight birds per replicate. Broilers in the control group were reared at a thermoneutral temperature and received a basal diet. Broilers in the other two heat-stressed groups were fed a basal diet supplemented without (heat-stressed group) and with 1.5 g/kg synbiotic (synbiotic group). One and a half gram of the synbiotic consisted with 3 × 109 colony forming units (CFU) Clostridium butyricum, 1.5 × 109 CFU Bacillus licheniformis, 4.5 × 1010 CFU Bacillus subtilis, 600 mg yeast cell wall, and 150 mg xylooligosaccharide. Compared with the control group, heat stress increased rectal temperatures at 28, 35, and 42 days of age, respectively (P < 0.05). Birds subjected to heat stress had reduced weight gain, feed intake, and feed efficiency during 22 to 42 days (P < 0.05). In contrast, supplementation with the synbiotic decreased rectal temperature at 42 days of age and elevated weight gain of heat stress-challenged broilers (P < 0.05). Heat-stressed broilers exhibited a lower superoxide dismutase (SOD) activity in jejunal mucosa and a higher malondialdehyde accumulation in serum, liver and jejunal mucosa (P < 0.05), and the regressive SOD activity was normalized to control level when supplementing synbiotic (P < 0.05). Heat stress increased interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ) levels in serum and IL-1ß content in jejunal mucosa of broilers (P < 0.05). Synbiotic reduced IL-1ß level in serum of broilers subjected to heat stress (P < 0.05). Compared with the control group, elevated serum diamine oxidase activity and reduced jejunal villus height were observed in broilers of the heat-stressed group (P < 0.05), and the values of these two parameters in the synbiotic group were intermediate (P > 0.05). Heat stress upregulated mRNA abundance of IL-1ß and IFN-γ and downregulated gene expression levels of occluding and zonula occluden-1 (ZO-1) in jejunal mucosa of broilers (P < 0.05). The alterations in the mRNA expression levels of jejunal IL-1ß and ZO-1 were reversed by the synbiotic (P > 0.05). In conclusion, dietary synbiotics could improve growth performance, antioxidant capacity, immune function, and intestinal barrier function in heat-stressed broilers.

Preliminary design and evaluation of a generic surgical scope adapter.

BACKGROUND: Robotic scope assistant systems are used to visualise and navigate the operative field during a laparoscopic surgery. The objective of this work is to design a surgical scope adapter that enables control of different scope types (zero-degree, angulated, and articulated), and can be connected to any six degree-of-freedom robotic manipulator for usage as a robotic scope assistant system. METHODS: A surgical scope adapter compatible with different camera heads and scope types was designed and prototyped. The technical performance of the scope adapter was evaluated and a user study was conducted to assess the human-in-the-loop control. RESULTS: All the subjects were able to navigate the simulated operative field. The scope adapter permits continuous motion to explore the operative field as well as intermittent motion to accurately focus on the targeted anatomical landmarks. CONCLUSION: The modular and generic nature of the surgical scope adapter may enable its usage across different minimally invasive surgeries.

Bead-jet printing enabled sparse mesenchymal stem cell patterning augments skeletal muscle and hair follicle regeneration.

Transplantation of mesenchymal stem cells (MSCs) holds promise to repair severe traumatic injuries. However, current transplantation practices limit the potential of this technique, either by losing the viable MSCs or reducing the performance of resident MSCs. Herein, we design a "bead-jet" printer, specialized for high-throughput intra-operative formulation and printing of MSCs-laden Matrigel beads. We show that high-density encapsulation of MSCs in Matrigel beads is able to augment MSC function, increasing MSC proliferation, migration, and extracellular vesicle production, compared with low-density bead or high-density bulk encapsulation of the equivalent number of MSCs. We find that the high-density MSCs-laden beads in sparse patterns demonstrate significantly improved therapeutic performance, by regenerating skeletal muscles approaching native-like cell density with reduced fibrosis, and regenerating skin with hair follicle growth and increased dermis thickness. MSC proliferation within 1-week post-transplantation and differentiation at 3 - 4 weeks post-transplantation are suggested to contribute therapy augmentation. We expect this "bead-jet" printing system to strengthen the potential of MSC transplantation.

Reduced Expression of Voltage-Gated Sodium Channel Beta 2 Restores Neuronal Injury and Improves Cognitive Dysfunction Induced by Aß1-42.

Voltage-gated sodium channel beta 2 (Nav2.2 or Navß2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navß2 in amyloid-ß 1-42- (Aß1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navß2 knockdown restored neuronal viability of Aß1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aß42, sAPPα, and sAPPß, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aß degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navß2 plays crucial roles in the repair of neuronal injury induced by Aß1-42 both in vivo and in vitro.

Adjuvant chemoradiotherapy does not improve outcomes in patients with fistula-associated anal adenocarcinoma undergoing abdominoperineal resection.

Objective: Abdominoperineal resection (APR) is currently established as a standard treatment regimen for fistula-associated anal adenocarcinoma (FAAA), however, the efficacy of chemoradiotherapy (CRT) remains unclear. The aim of this study is to evaluate the role of CRT in patients with FAAA treated with APR through single-center experience and literature review. Methods: A retrospective review was performed on patients with FAAA consecutive treated in our institution from 2005 to 2022. In addition, a systematic literature search was performed using PubMed and MEDLINE. All patients with FAAA who received APR in our institution and reported in the literature were included and divided into three categories for statistical analysis: APR alone (APR group), neoadjuvant therapy combined APR (CRT+APR group), and APR combined postoperative therapy (APR+CRT group). Results: Fifteen patients with FAAA were identified from our retrospective charts review. At a median follow-up time of 18 months, the recurrence-free survival rate was 53.3% and the survival rate was 73.3%. Eight patients underwent APR and 6 received postoperative chemotherapy. Among them, one died, one developed recurrence and the remaining six patients were alive with disease free. We found 37 publications describing 62 patients with FAAA treated with APR. Clinical data from these articles were analyzed together with the 8 cases in our institution. The overall survival rates were 94.1%, 70.8%, and 38.5% at 1-, 3-, 5-years respectively. Combining (neo)adjuvant therapy did not appear to improve outcomes in FAAA treated with APR (CRT+APR vs. APR, p=0.977; APR+CRT vs. APR, p=0.351). Lymph node involvement was shown to be significantly associated with poor outcomes by multivariate analysis (p=0.020). Conclusions: For patients with FAAA without lymph node involvement, APR is adequate to control disease and the addition of CRT does not appear to prolong survival.

Inverted papilloma and nasal polyp classification using a deep convolutional network integrated with an attention mechanism.

BACKGROUND: Inverted papilloma (IP) is a common sinus neoplasm with a probability of malignant transformation. Nasal polyps (NP) are the most frequent masses in the sinus. The classification of IP and NP using computed tomography (CT) is highly significant for preoperative recognition, treatment, and clinical examination. Few visible differences exist between IP and NP in CT, making it a challenge for otolaryngologists to distinguish between them. This study intended to classify IP and NP using a neural network and analyze its ability to discriminate the differences. METHODS: IP and NP in CT were classified using a deep convolutional neural network (CNN) with an attention mechanism, which combines a densely connected convolutional network (DenseNet) and squeeze-and-excitation network (SENet). Using SENet's channel attention, the specific channel weights in the feature maps are improved, which can enhance feature discriminativeness. To discuss the interpretability of SE-DenseNet, we analyzed the heatmap of the final convolutional layer. RESULTS: We evaluated the classification performance of SE-DenseNet on a clinical dataset containing 3382 slices for 136 patients. The experimental results and a heatmap show that SE-DenseNet can effectively locate sinonasal lesions in patients and distinguish IP from NP with an average Acc of 88.4% and AUC of 0.87. CONCLUSION: Otolaryngologists can use the proposed model to diagnose IP and NP in CT because of its accuracy and efficiency. Moreover, the visualized heatmaps produced by the convolutional layers show that the method is reliable.

A Time-Varying Model for Predicting Formaldehyde Emission Rates in Homes.

Recent studies have succeeded in relating emissions of various volatile organic compounds to material mass diffusion transfer using detailed empirical characteristics of each of the individual emitting materials. While significant, the resulting models are often scenario specific and/or require a host of individual component parameters to estimate emission rates. This study developed an approach to estimate aggregated emissions rates based on a wide number of field measurements. We used a multi-parameter regression model based on previous mass transfer models to predict formaldehyde emission rate for a whole dwelling using field-measured, time-resolved formaldehyde concentrations, air exchange rates, and indoor environmental parameters in 63 California single-family houses built between 2011 and 2017. The resulting model provides time-varying formaldehyde emission rates, normalized by floor area, for each study home, assuming a well-mixed mass balance transport model of the home, and a well-mixed layer transport model of indoor surfaces. The surface layer model asserts an equilibrium concentration within the surface layer of the emitted materials that is a function of temperature and RH; the dwelling ventilation rate serves as a surrogate for indoor concentration. We also developed a more generic emission model that is suitable for broad prediction of emission for a population of buildings. This model is also based on measurements aggregated from 27 homes from the same study. We showed that errors in predicting household formaldehyde concentrations using this approach were substantially less than those using a traditional constant emission rate model, despite requiring less unique building information.