Miracle-dz/UniFAR-FTUs huggingface dataset:
A randomized phase II trial of hepatic arterial infusion of oxaliplatin plus raltitrexed versus oxaliplatin plus 5-fluorouracil for unresectable colorectal cancer liver metastases

Background The purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM). Methods Patients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events. Results 113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838–6.762]) and 4.6 months [95% CI, 3.419–5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828–21.372] and 13.1 months [95% CI, 11.215–14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms. Conclusion HAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time. Clinical Trial Registration https://clinicaltrials.gov/, identifier NCT02557490.
Lipid droplet accumulation in β cells in patients with type 2 diabetes is associated with insulin resistance, hyperglycemia and β cell dysfunction involving decreased insulin granules

Background and objective Pancreatic fat is a form of ectopic fat. Lipid droplets (LDs) are also observed in β cells; however, the pathophysiological significance, especially for β cell function, has not been elucidated. Our aim was to assess LD accumulation in β cells in various stages of glucose intolerance and to clarify its relationship with clinical and histological parameters. Methods We examined 42 Japanese patients who underwent pancreatectomy. The BODIPY493/503-positive (BODIPY-positive) area in β cells was measured in pancreatic sections from 32 patients. The insulin granule numbers were counted in an additional 10 patients using electron microscopy. Results The BODIPY-positive area in β cells in preexisting type 2 diabetes patients was higher than that in normal glucose tolerance patients (p = 0.031). The BODIPY-positive area in β cells was positively correlated with age (r = 0.45, p = 0.0097), HbA1c (r = 0.38, p = 0.0302), fasting plasma glucose (r = 0.37, p = 0.045), and homeostasis model assessment insulin resistance (r = 0.41, p = 0.049) and negatively correlated with an increase in the C-peptide immunoreactivity level by the glucagon test (r = -0.59, p = 0.018). The ratio of mature insulin granule number to total insulin granule number was reduced in the patients with rich LD accumulation in β cells (p = 0.039). Conclusions Type 2 diabetes patients had high LD accumulation in β cells, which was associated with insulin resistance, hyperglycemia, aging and β cell dysfunction involving decreased mature insulin granules.
Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence: A multicenter retrospective study

Background Early recurrence is common after surgical resection (SR) for hepatocellular carcinoma (HCC) with high risk of recurrence and is associated with poor prognosis. The combinations of lenvatinib (LEN), anti-PD-1 antibodies (PD-1) and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. It is unknown whether triple therapy for neoadjuvant treatment of resectable HCC with high risk of recurrence is effective. This article aimed to compare the outcomes of surgery alone and neoadjuvant combination treatment with triple therapy before SR in patients with HCC with high risk of recurrence. Methods A retrospective study was conducted on patients diagnosed with HCC with high risk of recurrence who received treatment with or without triple therapy. The records of 24 patients in the triple therapy group and 76 patients in the surgery-alone group were analyzed. Propensity score matching (PSM) was performed to minimize the influence of potential confounders. Results One hundred patients were enrolled. In the triple therapy group, 8 (33.3%) and 12 (50.0%) patients had complete and partial responses, respectively, as assessed by an investigator. Before PSM, the overall survival (OS) rates for the triple therapy group at 6, 12, 18, and 24 months were 100.0%, 100.0%, 100.0%, and 85.7%, respectively, compared with corresponding 92.1%, 73.7%, 53.9%, and 48.7% for the surgery-alone group (P<0.001). The disease-free survival (DFS) rates were 82.2%, 66.95%, 48.8%, and 48.8% for the triple therapy and 41.92%, 28.34%, 27.05%, and 22.99% for the surgery-alone group (P=0.003). After PSM, DFS and OS were significantly longer in the triple therapy group than in the surgery-alone group (DFS, p=0.019; OS, p=0.003). Conclusions Neoadjuvant combination treatment before SR had a high rate of tumor response and provided significantly better postoperative survival outcomes than surgery alone in patients with HCC with high risk of recurrence.
First generation of multifunctional peptides derived from latarcin-3a from Lachesana tarabaevi spider toxin

The need for discovering new compounds that can act selectively on pathogens is becoming increasingly evident, given the number of deaths worldwide due to bacterial infections or tumor cells. New multifunctional biotechnological tools are being sought, including compounds present in spider venoms, which have high biotechnological potential. The present work aims to perform the rational design and functional evaluation of synthetic peptides derived from Lachesana tarabaevi spider toxin, known as latarcin-3a. The antimicrobial activity was tested against Gram-positive and -negative bacteria, with minimum inhibitory concentrations (MIC) between 4 and 128 μg. ml−1. Anti-biofilm tests were then performed to obtain MICs, where the peptides demonstrated activity from 4 to 128 μg. ml−1. In vitro cell cytotoxicity assays were carried out from tumor cell lines, lineages C1498, Kasumi-1, K-562, Jurkat, MOLT4, and Raji. Erythrocyte integrity was evaluated in the presence of synthetic peptides analog, which did not promote hemolysis at 128 μg. ml−1. The peptide that showed the best antibacterial activity was Lt-MAP3 and the best antitumor was Lt-MAP2. In conclusion, rational design of multifunctional antimicrobial peptides may be promising alternative tools in the treatment of emerging diseases such as bacterial infections and tumor cells.
Could AMPs and B-cells be the missing link in understanding periodontitis?

Periodontal diseases are common inflammatory conditions characterized by bone loss in response to simultaneous bacterial aggression and host defenses. The etiology of such diseases is still not completely understood, however. It has been shown that specific pathogens involved in the build-up of dysbiotic biofilms participate actively in the establishment of periodontitis. This multifactorial pathology also depends on environmental factors and host characteristics, especially defenses. The immune response to the pathogens seems to be critical in preventing the disease from starting but also contributes to tissue damage. It is known that small molecules known as antimicrobial peptides (AMPs) are key actors in the innate immune response. They not only target microbes, but also act as immuno-modulators. They can help to recruit or activate cells such as neutrophils, monocytes, dendritic cells, or lymphocytes. AMPs have already been described in the periodontium, and their expression seems to be connected to disease activity. Alpha and beta defensins and LL37 are the AMPs most frequently linked to periodontitis. Additionally, leukocyte infiltrates, especially B-cells, have also been linked to the severity of periodontitis. Indeed, the particular subpopulations of B-cells in these infiltrates have been linked to inflammation and bone resorption. A link between B-cells and AMP could be relevant to understanding B-cells’ action. Some AMP receptors, such as chemokines receptors, toll-like receptors, or purinergic receptors, have been shown to be expressed by B-cells. Consequently, the action of AMPs on B—cell subpopulations could participate to B-cell recruitment, their differentiation, and their implication in both periodontal defense and destruction.
Exploring food waste prevention through advent food consumption: The role of perceived concern, consumer value, and impulse buying

Every year, about one-third of food intended for human consumption is wasted along the distribution chain, in which advent food contributes a significant portion. Advent food marketing and consumption are suggested as the primary channel to use advent food and reduce food waste. With the booming of the advent food market, it is necessary to explore factors attributed to advent food purchase and food waste reduction behaviors. This study explored what consumer concern and value might influence food waste reduction intention in the context of advent food consumption. Based on a survey of Chinese consumers (N = 509), this study develops a structural equation and tests the hypotheses with consistent Smart-pls software. Results show that, as expected, health concerns, utilitarian value, and impulse buying significantly affect food waste reduction intention. Price concern, utilitarian value, and hedonic value exert direct positive effects on impulse buying, which negatively influence food waste reduction intention. In the mediating effect analysis, impulse buying partially mediates the relationship between price concern and food waste reduction intention. Theoretical and managerial implications and recommendations for future research are discussed.
Bioinformatic analysis of the LCN2–SLC22A17–MMP9 network in cancer: The role of DNA methylation in the modulation of tumor microenvironment

Several features of cancer cells such as proliferation, invasion, metastatic spreading, and drug resistance are affected by their interaction with several tumor microenvironment (TME) components, including neutrophil gelatinase-associated lipocalin (NGAL), solute carrier family 22 member 17 (SLC22A17), and matrix metallopeptidase 9 (MMP9). These molecules play a key role in tumor growth, invasion, and iron-dependent metabolism of cancer cells. However, the precise epigenetic mechanisms underlying the gene regulation of Lipocalin 2 (LCN2), SLC22A17, and MMP9 in cancer still remain unclear. To this purpose, computational analysis was performed on TCGA and GTEx datasets to evaluate the expression and DNA methylation status of LCN2, SLC22A17, and MMP9 genes in different tumor types. Correlation analysis between gene/isoforms expression and DNA methylation levels of LCN2, SLC22A17, and MMP9 was performed to investigate the role of DNA methylation in the modulation of these genes. Protein network analysis was carried out using reverse phase protein arrays (RPPA) data to identify protein–protein interactions of the LCN2–SLC22A17–MMP9 network. Furthermore, survival analysis was performed according to gene expression and DNA methylation levels. Our results demonstrated that LCN2 and MMP9 were mainly upregulated in most tumor types, whereas SLC22A17 was largely downregulated, representing a specific hallmark signature for all gastrointestinal tumors. Notably, the expression of LCN2, SLC22A17, and MMP9 genes was negatively affected by promoter methylation. Conversely, intragenic hypermethylation was associated with the overexpression of SLC22A17 and MMP9 genes. Protein network analysis highlighted the role of the LCN2–SLC22A17–MMP9 network in TME by the interaction with fibronectin 1 and claudin 7, especially in rectal tumors. Moreover, the impact of expression and methylation status of LCN2, SLC22A17, and MMP9 on overall survival and progression free interval was tumor type–dependent. Overall, our analyses provide a detailed overview of the expression and methylation status of LCN2, SLC22A17, and MMP9 in all TCGA tumors, indicating that the LCN2–SLC22A17–MMP9 network was strictly regulated by DNA methylation within TME. Our findings pave the way for the identification of novel DNA methylation hotspots with diagnostic and prognostic values and suitable for epi-drug targeting.
Stem canker pathogen Botryosphaeria dothidea inhibits poplar leaf photosynthesis in the early stage of inoculation

Fungal pathogens can induce canker lesions, wilting, and even dieback in many species. Trees can suffer serious physiological effects from stem cankers. In this study, we investigated the effects of Botryosphaeria dothidea (B. dothidea) on Populus bolleana (P. bolleana) leaves photosynthesis and stomatal responses, when stems were inoculated with the pathogen. To provide experimental and theoretical basis for preventing poplar canker early. One-year-old poplar stems were inoculated with B. dothidea using an epidermal scraping method. In the early stage of B. dothidea inoculation (2–14 days post inoculation, dpi), the gas exchange, stomatal dynamics, hormone content, photosynthetic pigments content, chlorophyll fluorescence parameters, and non-structural carbohydrate (NSC) were evaluated to elucidate the pathophysiological mechanism of B. dothidea inhibiting photosynthesis. Compared with the control groups, B. dothidea noteworthily inhibited the net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (Tr), and other photosynthetic parameters of poplar leaves, but stomatal limit value (Ls) increased. Consistent with the above results, B. dothidea also reduced stomatal aperture and stomatal opening rate. In addition, B. dothidea not only remarkably reduced the content of photosynthetic pigments, but also decreased the maximum photochemical efficiency (Fv/Fm), actual photochemical efficiency (ΦPSII), electron transfer efficiency (ETR), and photochemical quenching coefficient (qP). Furthermore, both chlorophyll and ΦPSII were positively correlated with Pn. In summary, the main reason for the abated Pn under stem canker pathogen was that B. dothidea not merely inhibited the stomatal opening, but hindered the conversion of light energy, electron transfer and light energy utilization of poplar leaves. In general, the lessened CO2 and Pn would reduce the synthesis of photosynthetic products. Whereas, sucrose and starch accumulated in poplar leaves, which may be due to the local damage caused by B. dothidea inoculation in phloem, hindering downward transport of these products.
Effect of hot etching with HF on the surface topography and bond strength of zirconia

Zirconia has occupied an increasingly important role in oral clinical applications in recent years. However, how to achieve the ideal bonding effect of zirconia is a significant problem that needs to be solved urgently in oral clinics. Hot etching treatment of zirconia is a hot spot of current research, but it is still unclear about the optimal acid solution and the effect of hot etching on the surface topography and bond strength of zirconia. This study evaluated the effect of hot etching with HF and HCl on the surface topography, roughness, crystalline phase, zirconia/resin cement interfacial evaluation and shear bond strength of zirconia. The results showed that the hot etching groups produced completely different topographical changes on the surface of zirconia than the sandblasting group. Obvious interfacial cracks were observed in the sandblasting group. The HF hot etching group achieved the highest roughness values (78.17 ± 4.94 nm) and the highest shear bond strength (25.09 ± 4.09 MPa). Compared with HCl, hot etching with HF could achieve more uniform and dense porous morphology, greater roughness and shear bond strength. Moreover, there were no prominent zirconia/resin cement interfacial cracks and crystal phase transformations on the surface of zirconia.
Mechanisms of lymphoid depletion in bowel obstruction

Background and aims: Bowel obstruction (BO) causes not only gastrointestinal dysfunctions but also systemic responses such as sepsis, infections, and immune impairments. The mechanisms involved are not well understood. In this study, we tested the hypothesis that BO leads to lymphoid depletion in primary and peripheral lymphoid organs, which may contribute to systemic responses. We also sought to uncover mechanisms of lymphoid depletion in BO. Methods: Partial colon obstruction was induced with a band in the distal colon of Sprague-Dawley rats, and wild-type and osteopontin knockout (OPN−/−) mice. Obstruction was maintained for 7 days in rats and 4 days in mice. Thymus, bone marrow, spleen, and mesenteric lymph node (MLN) were taken for flow cytometry analysis. Results: The weight of thymus, spleen, and MLN was significantly decreased in BO rats, compared to sham. B and T lymphopoiesis in the bone marrow and thymus was suppressed, and numbers of lymphocytes, CD4+, and CD8+ T cells in the spleen and MLN were all decreased in BO. Depletion of gut microbiota blocked BO-associated lymphopenia in the MLN. Corticosterone antagonism partially attenuated BO-associated reduction of lymphocytes in the thymus and bone marrow. Plasma OPN levels and OPN expression in the distended colon were increased in BO. Deletion of the OPN gene did not affect splenic lymphopenia, but attenuated suppression of lymphopoiesis in the bone marrow and thymus in BO. Conclusions: BO suppresses lymphocyte generation and maintenance in lymphoid organs. Mechanical distention-induced OPN, corticosterone, and gut microbiota are involved in the immune phenotype in BO.
Hepatoprotective potential of a novel quinazoline derivative in thioacetamide-induced liver toxicity

Purpose: The compound quinazoline Q-Br, 3-(5-bromo-2-hydroxybenzylideneamino)-2-(5-bromo-2 hydroxyphenyl) 2,3-dihydroquinazoline-4(1H)-one (Q-Br) was evaluated for its antioxidant capacity and potential hepatoprotectivity against sub-chronic liver toxicity induced by thioacetamide in rats. Materials and Methods: Rats were assigned into five groups; healthy (normal) and cirrhosis control groups were given 5% Tween 20 orally, the reference control group was given a Silymarin dose of 50 mg/kg, and low-dose Q-Br and high-dose Q-Br groups were given a daily dose of 25 mg/kg and 50 mg/g Q-Br, respectively. Liver status was detected via fluorescence imaging with intravenous injection of indocyanine green (ICG) and a plasma ICG clearance test. Liver malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were also tested. The degree of fibrosis was determined histologically by hematoxylin and eosin and Masson’s Trichrome staining. The immunohistochemistry of liver tissue inhibitor of metalloproteinase (TIMP-1), matrix metalloproteinase (MMP-2), and alpha-smooth muscle actin (α-SMA) was performed. Results: Q-Br recorded mild antioxidant capacity, dose-dependent improvement in the liver status, and inhibition of oxidative stress compared to cirrhosis control. Histopathology notified a remarkable reduction in the degree of fibrosis. Immunohistochemistry revealed an obvious low expression of MMP-2 and α-SMA along with a higher expression of TIMP-1 in Q-Br- and Silymarin-treated livers. Conclusion: Q-Br treatment altered the course of toxicity induced by thioacetamide suggesting significant hepatoprotective potential of Q-Br treatment.
An ensemble learning approach to map the genetic connectivity of the parasitoid Stethynium empoasca (Hymenoptera: Mymaridae) and identify the key influencing environmental and landscape factors

The effect of landscape patterns and environmental factors on the population structure and genetic diversity of organisms is well-documented. However, this effect is still unclear in the case of Mymaridae parasitoids. Despite recent advances in machine learning methods for landscape genetics, ensemble learning still needs further investigation. Here, we evaluated the performance of different boosting algorithms and analyzed the effects of landscape and environmental factors on the genetic variations in the tea green leafhopper parasitoid Stethynium empoasca (Hymenoptera: Mymaridae). The S. empoasca populations showed a distinct pattern of isolation by distance. The minimum temperature of the coldest month, annual precipitation, the coverage of evergreen/deciduous needleleaf trees per 1 km2, and the minimum precipitation of the warmest quarter were identified as the dominant factors affecting the genetic divergence of S. empoasca populations. Notably, compared to previous machine learning studies, our model showed an unprecedented accuracy (r = 0.87) for the prediction of genetic differentiation. These findings not only demonstrated how the landscape shaped S. empoasca genetics but also provided an essential basis for developing conservation strategies for this biocontrol agent. In a broader sense, this study demonstrated the importance and efficiency of ensemble learning in landscape genetics.
Climate change stress alleviation through nature based solutions: A global perspective

Global climate change stress has greatly influenced agricultural crop production which leads to the global problems such as food security. To cope with global climate change, nature based solutions (NBS) are desirable because these lead to improve our environment. Environmental stresses such as drought and salinity are big soil problems and can be eradicated by increasing soil organic matter which is directly related to soil organic carbon (SOC). SOC is one of the key components of the worldwide carbon (C) cycle. Different types of land use patterns have shown significant impacts on SOC stocks. However, their effects on the various SOC fractions are not well-understood at the global level which make it difficult to predict how SOC changes over time. We aim to investigate changes in various SOC fractions, including mineral associated organic carbon (MAOC), mineral associated organic matter (MAOM), soil organic carbon (SOC), easily oxidized organic carbon (EOC), microbial biomass carbon (MBC) and particulate organic carbon (POC) under various types of land use patterns (NBS), including cropping pattern, residue management, conservation tillages such as no tillage (NT) and reduced tillage (RT) using data from 97 studies on a global scale. The results showed that NT overall increased MAOC, MAOM, SOC, MBC, EOC and POC by 16.2%, 26.8%, 24.1%, 16.2%, 27.9% and 33.2% (P < 0.05) compared to CT. No tillage with residue retention (NTR) increased MAOC, MAOM, SOC, MBC, EOC and POC by 38.0%, 29.9%, 47.5%, 33.1%, 35.7% and 49.0%, respectively, compared to CT (P < 0.05). RT overall increased MAOC, MAOM, SOC, MBC, EOC and POC by 36.8%, 14.1%, 25.8%, 25.9, 18.7% and 16.6% (P < 0.05) compared to CT. Reduced tillage with residue retention (RTR) increased MAOM, SOC and POC by 14.2%, 36.2% and 30.7%, respectively, compared to CT (P < 0.05). Multiple cropping increased MAOC, MBC and EOC by 14.1%, 39.8% and 21.5%, respectively, compared to mono cropping (P < 0.05). The response ratios of SOC fractions (MAOC, MAOM, SOC, MBC, EOC and POC) under NT and RT were mostly influenced by NBS such as residue management, cropping pattern along with soil depth, mean annual precipitation, mean annual temperature and soil texture. Our findings imply that when assessing the effects of conservation tillage methods on SOC sequestration, SOC fractions especially those taking part in driving soil biological activities, should be taken into account rather than total SOC. We conclude that conservation tillages under multiple cropping systems and with retention of crop residues enhance soil carbon sequestration as compared to CT in varying edaphic and climatic conditions of the world.