TMODINET: A trustworthy multi-omics dynamic learning integration network for cancer diagnostic.

Multiple types of omics data contain a wealth of biomedical information which reflect different aspects of clinical samples. Multi-omics integrated analysis is more likely to lead to more accurate clinical decisions. Existing cancer diagnostic methods based on multi-omics data integration mainly focus on the classification accuracy of the model, while neglecting the interpretability of the internal mechanism and the reliability of the results, which are crucial in specific domains such as precision medicine and the life sciences. To overcome this limitation, we propose a trustworthy multi-omics dynamic learning framework (TMODINET) for cancer diagnostic. The framework employs multi-omics adaptive dynamic learning to process each sample to provide patient-centered personality diagnosis by using self-attentional learning of features and modalities. To characterize the correlation between samples well, we introduce a graph dynamic learning method which can adaptively adjust the graph structure according to the specific classification results for specific graph convolutional networks (GCN) learning. Moreover, we utilize an uncertainty mechanism by employing Dirichlet distribution and Dempster-Shafer theory to obtain uncertainty and integrate multi-omics data at the decision level, ensuring trustworthy for cancer diagnosis. Extensive experiments on four real-world multimodal medical datasets are conducted. Compared to state-of-the-art methods, the superior performance and trustworthiness of our proposed algorithm are clearly validated. Our model has great potential for clinical diagnosis.

LncRNA ILF3-AS1 mediates oxidative stress and inflammation through miR-504-3p/HMGB1 axis in a cellular model of temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE), a prevalent neurological disorder, is associated with hippocampal oxidative stress and inflammation. A recent study reveals that the long noncoding RNA ILF3 divergent transcript (ILF3-AS1) level is elevated in the hippocampus of TLE patients; however, the functional roles of ILF3-AS1 in TLE and underlying mechanisms deserve further investigation. Hence, this study aimed to elucidate whether ILF3-AS1 is involved in the pathogenesis of TLE by regulating oxidative stress and inflammation and to explore its underlying mechanism in vitro. METHODS: Human hippocampal neurons were subjected to a magnesium-free (Mg2+-free) solution to establish an in vitro model of TLE. The potential binding sites between ILF3-AS1 and miRNA were predicted by TargetScan/Starbase and confirmed by dual luciferase reporter assay. Cell viability and damage were assessed by cell counting kit-8 and lactate dehydrogenase assay kits, respectively. Levels of reactive oxygen species, malondialdehyde, and superoxide dismutase were determined by commercial kits. Levels of Interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-alpha were quantified by enzyme-linked immunosorbent assay. The expressions of gene and protein were determined by quantitative real-time polymerase chain reaction and Western blot analysis. RESULTS: In Mg2+-free-treated hippocampal neurons, both ILF3-AS1 and HMGB1 were highly up-regulated, whereas miR-504-3p was down-regulated. ILF3-AS1 knockdown ameliorated Mg2+-free-induced cellular damage, oxidative stress, and inflammatory response. Bioinformatics analysis revealed that miR-504-3p was a target of ILF3-AS1 and was negatively regulated by ILF3-AS1. MiR-504-3p inhibitor blocked the protection of ILF3-AS1 knockdown against Mg2+-free-induced neuronal injury. Further analysis presented that ILF3-AS1 regulated HMGB1 expression by sponging miR-504-3p. Moreover, HMGB1 overexpression reversed the protective functions of ILF3-AS1 knockdown. CONCLUSION: Our findings indicate that ILF3-AS1 contributes to Mg2+-free-induced hippocampal neuron injuries, oxidative stress, and inflammation by targeting the miR-504-3p/HMGB1 axis. These results provide a novel mechanistic understanding of ILF3-AS1 in TLE and suggest potential therapeutic targets for the treatment of epilepsy.

2-(3,4-dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB) ameliorates cognitive dysfunction via modulating gut microbiota in aged senescence-accelerated mouse prone 8 (SAMP8) mice.

Numerous studies have indicated a close association between gut microbiota dysbiosis, inflammation, and cognitive impairment, highlighting their crucial role in the aging process. 2-(3,4-Dihydroxyphenyl)ethyl 3-hydroxybutanoate (HTHB), a novel derivative of hydroxytryrosol (HT), known for its metabolic and anti-inflammatory properties, was investigated for its effects on memory, inflammation, and gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. The study employed behavioral testing, biochemical detection and 16S RNA analysis. Results revealed that HTHB mitigated memory decline and lymphocyte aberrance, reduced inflammation in the brain cortex, intestine and peripheral system, and modulated gut microbiota dysbiosis. Interestingly, the cognitive function and serum inflammation of mice significantly correlated with differences in gut microbiota in SAMP8 mice. Furthermore, HTHB treatment exhibited an enhancement of gut barrier integrity in colon tissue in SAMP8 mice. In vitro experiments using HCT116 and DLD1 cells further evidenced that HTHB rescued the tight junction protein levels impaired by lipopolysaccharide (LPS). These finding demonstrate that HTHB effectively ameliorates cognitive dysfunction in aged mice, might by modulating gut microbiota, suppressing inflammation and promoting intestinal barrier integrity. This highlights the potential of HTHB as a therapeutic agent for age-related cognitive loss.

Host-derived lactic acid bacteria alleviate short beak and dwarf syndrome by preventing bone loss, intestinal barrier disruption, and inflammation.

Short-beak and dwarf syndrome (SBDS) is caused by novel goose parvovirus (NGPV) infection, which leads to farm economic losses. Our research aimed to investigate the potential of administering isolated lactic acid bacteria (LAB) in alleviating SBDS in ducks. Eight wild LAB strains were isolated from duck feces and their biosecurity was investigated in both duck embryo fibroblast (DEF) and live ducks. Moreover, the LAB strains exhibited no detrimental effects on bone metabolism levels and facilitated the tight junction proteins (TJPs) mRNA expression, and contributing to the mitigation of inflammation in healthy ducks. Subsequently, we conducted in vitrol and in vivo experiments to assess the impact of LAB on NGPV infection. The LAB strains significantly reduced the viral load of NGPV and downregulated the mRNA levels of pro-inflammatory factors in DEF. Additionally, LAB treatment alleviated SBDS in NGPV-infected ducks. Furthermore, LAB treatment alleviated intestinal damage, and reduced the inflammatory response, while also mitigating bone resorption in NGPV-infected ducks. In conclusion, the LAB strains isolated from duck feces have favorable biosecurity and alleviate SBDS in ducks, and the mechanism related to LAB improves intestinal barrier integrity, alleviates inflammation, and reduces bone resorption. Our study presents a novel concept for the prevention and treatment of NGPV, thereby establishing a theoretical foundation for the future development of probiotics in the prevention and treatment of NGPV.

Trade-offs of reproductive growth and Cd remobilization regulated Cd accumulation in wheat grains (Triticum aestivum L.).

Minimization of cadmium (Cd) accumulation in wheat grain (Triticum aestivum L.) is an important way to prevent Cd hazards to humans. However, little is known about the mechanisms of varietal variation of Cd accumulation in wheat grain. This study explores the physiological mechanisms of Cd bioaccumulation through field and hydroponic experiments on two wheat varieties of low-Cd-accumulating variety (L-6331) and high-Cd-accumulating variety (H-6049). Field study showed that average Cd accumulative rates in spikes of H-6049 were 1.57-fold of L-6331 after flowering, ultimately grain-Cd of H-6049 was 1.70-fold of L-6331 in Cd-contaminated farmland. The hydroponic experiment further confirmed that more vegetative tissues of L-6331 were involved in the remobilization of Cd, which jointly mitigated the process of Cd loaded to grains when leaf-cutting conducted after Cd stress. Additionally, the L1 and N1 of L-6331 play an especially important role in regulating Cd remobilization, and the larger EVB areas in N1 have the morphological feature that facilitates the transfer of Cd to L1. Overall results implied that low-Cd-accumulating variety initiated more trade-offs of reproductive growth and Cd remobilizatoin under Cd-stress after flowering compared with high-Cd-accumulating variety, and provided new insights into the processes of Cd loaded into wheat grains among different varieties.

Characteristics of auto-quantified tumor-infiltrating lymphocytes and the prognostic value in adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, and esophageal squamous cell carcinoma.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEGJ) with a specific pathological profile and poor prognosis has limited therapeutic options. Previous studies have found that TILs exhibit distinct characteristics in different tumors and are correlated with tumor prognosis. We established cellular training sets to obtain auto-quantified TILs in pathological images. And we compared the characteristics of TILs in AEGJ with those in esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma (GAC) to gain insight into the unique immune environments of these three tumors and investigate the prognostic value of TILs in these three tumors. METHODS: Utilizing a case-control study design, we analyzed 214 AEGJ, 256 GAC, and 752 ESCC cases. The TCGA dataset was used to validate prognostic value of auto-quantified TILs. The specific cellular training sets were established by experienced pathologists to determine TILs counts. Kruskal-Wallis test and multi-variable linear regression were conducted to explore TILs characteristics. Survival analyses were performed with Kaplan-Meier method and Cox proportional hazards model. RESULTS: The three cellular training sets of these cancers achieved a classification accuracy of 87.55 at least. The median auto-quantified TILs of AEGJ, GAC, and ESCC cases were 4.82%, 1.92%, and 0.12%, respectively. The TILs demonstrated varied characteristics under distinctive clinicopathological traits. The higher TILs proportion was associated with better prognosis in esophagogastric cancers (all P < 0.05) and was an independent prognostic biomarker on AEGJ in both datasets (Taixing: HR = 0.965, 95% CI = 0.938-0.994; TCGA: HR = 0.811, 95% CI = 0.712-0.925). CONCLUSIONS: We found variations in TILs across ESCC, GAC, and AEGJ, as assessed by image processing algorithms. Additionally, TILs in these three cancers are an independent prognostic factor. This enhances our understanding of the unique immune characteristics of the three tumors, improving patient outcomes.

Foliar uptake screening: A promising strategy for identifying wheat varieties with low lead accumulation.

Lead (Pb) contamination in wheat grain is of great concern, especially in North China. Atmospheric deposition is a major contributor to Pb accumulation in wheat grain. Screening low Pb accumulating wheat varieties has been an effective method for addressing Pb contamination in wheat grain. However, identifying wheat varieties with low Pb accumulation based on foliar uptake of atmospheric Pb has been neglected. Therefore, two field trials with distinct atmospheric Pb deposition were conducted to screen for stable varieties with low Pb accumulation. It was verified that YB700 and CH58, which have high thousand-grain weights and stable low Pb accumulation in field 1 (0.19 and 0.13 mg kg-1) and field 2 (0.17 and 0.20 mg kg-1), respectively, were recommended for cultivation in atmospheric Pb contaminated farmlands in North China. Furthermore, indoor experiments were conducted to investigate Pb uptake by the roots and leaves of different wheat varieties. Our findings indicate that Pb accumulation in different wheat varieties is primarily influenced by foliar Pb uptake rather than root Pb uptake. Interestingly, there was a positive correlation (p < 0.05) between the Pb concentrations in leaves and the stomatal width and trichome length of the adaxial epidermal surface. Additionally, there is a positive correlation (p < 0.01) between the Pb concentration in the wheat grain and trichome length. In conclusion, the screening of wheat varieties with narrower stomatal widths or shorter trichomes based on foliar uptake pathways is an effective strategy for ensuring food safety in areas contaminated by atmospheric Pb.

[Blocking Effects of Foliar Conditioners on Cadmium, Arsenic, and Lead Accumulation in Wheat Grain in Compound-contaminated Farmland].

Heavy metal contamination of soil has become a hot issue of social concern due to its impact on the safety of agricultural products in recent years. Wheat is one of the most dominant staple food crops worldwide and has become a major source of toxic metals in human diets. Foliar application was considered to be a more efficient and economical method of heavy metal remediation. Field experiments were carried out in Cd-, As-, and Pb-contaminated farmland soils. The effects of foliar conditioners on the accumulation of Cd, As, and Pb in wheat grains were investigated after being sprayed with Zn (0.2% ZnSO4), Mg (0.4% MgSO4), and Mn (0.2% MnSO4) separately and in combination. Thus, the effective foliar conditioners were selected to block the accumulation of Cd, As, and Pb in wheat grains grown in combined heavy metal-contaminated farmland in north China. The results showed that, compared with that in the control, the Cd, As, and Pb contents in wheat grains of the Zn+Mg+Mn foliar treatment were significantly decreased by 18.96%, 23.87%, and 51.31%, respectively, and TFgrain/straw decreased by 14.62%, 27.73%, and 47.70%, respectively. Thus, spraying the compound foliar conditioner of Zn+Mg+Mn could effectively reduce heavy metal accumulation in wheat grains through inhibition translocation of those metals from stem leaves to grain. In addition, the results indicated that Cd and As were mainly distributed at the central endosperm (34.08%-37.08%), whereas Pb was primarily distributed at the pericarp and seed coat (27.78%) of the wheat grain. Compared with that in the control, spraying the compound foliar conditioner of Zn+Mg+Mn extremely decreased Cd and As accumulation in the aleurone layer of the wheat grain by 81.10% and 82.24%, respectively. Except for the pericarp, seed coat, and central endosperm layers, the Pb content in each grain layer was dramatically decreased by 42.85% to 91.15%. There was only a significant negative correlation between heavy metal content and Zn content in the aleurone layer (P2) of wheat flour. In summary, the accumulation of Cd, As, and Pb in wheat grains, especially in the aleurone layer, could be effectively reduced by foliar conditioner application at the jointing, booting, and early filling stages of wheat, separately. Furthermore, besides the foliar treatment, removing wheat bran to reduce Cd contamination in wheat grains is highly recommended to ensure the safe production of wheat.

Two new terpenoids from the branches and leaves of Rhododendron dauricum L. with neuroprotective activity.

Two new terpenoids were isolated from the branches and leaves of Rhododendron dauricum L., named as rhodayritions A (1) and B (2), together with five known compounds which were identified litseachromolaevane A (3), 11-αH-dihydrodehydrocostus lactone (4), (+)-9ß-hydroxyeudesma-4,11(13)-dien-12-al (5), macrostachyoside B (6) and aglaiabbreviatin E (7), respectively. The structures of isolated compounds were determined by UV, HR-ESI-MS, NMR analysis and X-Ray. Their neuroprotective activity was studied on serum deprivation-induced PC12 cells by the MTT method, compounds 1, 6, and 7 exhibited significant neuroprotective activity at 20 µΜ.

Roots recruited distinct rhizo-microbial communities to adapt to long-term Cd and As co-contaminated soil in wheat-maize rotation.

Cd and As accumulation in staple crops poses potential risks to food safety and human health. Rhizo-microbial communities are involved in their behaviors from soil to crops. However, the responses of rhizo-microbial communities to different Cd and As co-contaminated soils in wheat‒maize rotation are still unclear. This study explored whether wheat or maize could recruit distinct rhizo-microbial communities to adapt to long-term co-contaminated soils with low or high levels of Cd and As (LS or HS). It was apparent that the average wheat grain-Cd/As concentrations were 17.96-fold/4.81-fold in LS and 5.64-fold/7.70-fold in HS higher than those in maize grains, significantly depending on the mobility of Cd/As in soil-crop system, especially from soil to root and from straw to grain. Meanwhile, wheat or maize roots recruited specific bacteria and fungi in LS and HS, which were substantially associated with Cd/As bioavailability in rhizosphere. Wheat roots recruited specific bacterial genera norank_c__MB-A2-108 (Actinobacteria), norank_f__JG30-KF-CM45 (Chloroflexi), and norank_o__Rokubacteriales (Methylomirabilota) and fungal genera Metarhizium and Olpidium under HS, and their relative abundances were positively correlated with soil Cd/As bioavailability and were resistant to Cd and As co-contamination. However, bacterial genera Arthrobacter, Nocardioides, Devosia, Skermanella, and Pedobacter were sensitive to Cd and As co-contamination and were specifically enriched in wheat rhizospheres under LS. Meanwhile, the bacterial genus norank_c__KD4-96 (Chloroflexi) was resistant to Cd and As co-contamination under HS and was distinctly enriched in maize rhizosphere. Furthermore, the roots of wheat and maize recruited the bacterial genus Marmoricola in LS, which was sensitive to Cd and As co-contamination, and recruited specific fungal genus Fusicolla in HS, which was tolerant to Cd and As co-contamination. These results confirmed that HS and LS shifted the composition and structure of the rhizo-microbial communities in the wheat-maize rotation to promote crops survival in different long-term Cd and As co-contaminated soils.

Pyrolysis of municipal plastic waste: Chlorine distribution and formation of organic chlorinated compounds.

The release of chlorine during the pyrolysis of actual municipal plastic waste (MPW) was studied. Firstly, thermogravimetry-Fourier transform infrared (TG-FTIR) was analyzed to investigate the chlorine release behavior. Then, the effect of temperature on chlorine migrations was investigated by fast pyrolysis experiments in a fixed bed reactor. Results showed that chlorine released mainly between 241 and 353 °C in the form of HCl or chloroesters during MPW pyrolysis. After pyrolysis, chlorine was mainly distributed in the pyrolytic gas (74.34-82.89 %) and char (10.17-21.29 %). However, the release of chlorine was inhibited due to the melting behavior of MPW at <350 °C. Besides, the relative contents and types of organic chlorinated compounds in liquid products were both decreased with temperature. It was observed that polyethylene terephthalate (PET) was the greatest contributor to the formation of organic chlorinated compounds during MPW pyrolysis. Meanwhile, the pyrolysis of PET was significantly promoted by the HCl released from polyvinyl chloride (PVC). Subsequently, the pathways for the formation of organic chlorinated compounds through the co-pyrolysis of PVC and PET were proposed, including the initial degradation and subsequent chlorination of PET. These findings provided new insights into the release and regulation of chlorine-containing pollutants during actual MPW pyrolysis.

Migration characteristics of chlorine during pyrolysis of municipal solid waste pellets.

The migration process of chlorine during municipal solid waste (MSW) pellets pyrolysis was studied in a fixed bed reactor. Distribution and speciation changes of chlorine at different pyrolysis temperatures were determined by ion chromatography (IC) and X-ray photoelectron spectroscopy (XPS) analyses. Results showed that chlorine was mainly distributed in pyrolysis char (42.36-65.29 %) and gas (26.66-35.03 %) after MSW pellets pyrolysis. With the temperature increasing, chlorine in char and tar was enriched due to the increase of chlorine release and the decrease of product yields, with chlorine concentration increasing to 3498 ppm and 1415 ppm at 800 °C, respectively. Results of chlorine forms analysis indicated that most of the organic-Cl in MSW was released into the volatiles during pyrolysis due to the dissociation of CCl. Inorganic-Cl became the dominant form of chlorine in char after pyrolysis, with the proportion increasing from 46.69 % (raw) to 61.22 % (500 °C), which also suggested that part of organic-Cl was converted into the inorganic-Cl. Notably, the proportions of inorganic-Cl decreased at >600 °C due to the migration of inorganic. In addition, the pyrolysis release behavior of chlorine was affected by the pore structure of char, which could be inhibited by the unprosperous pores in char, especially at low temperatures (<600 °C). These findings provided a reference for the chlorine regulation of MSW pyrolytic products.

Comparative evolutionary and molecular genetics based study of Buffalo lysozyme gene family to elucidate their antibacterial function.

Lysozyme is used as a food preservative, biological medicine, and infant food additive as a natural anti-infective chemical having bactericidal activity and abundantly secreted in mammals' milk, saliva, etc. We systematically analyzed the 16 coding LYZ genes (C and G-type) in buffalo and cattle to elucidate their evolutionary perspective thoroughly by evaluating an evolutionary relationship, motif patterning, physicochemical attributes, gene, and protein structure, as well as the functional role of the mammary gland-specific expressed buffalo and cattle LYZ genes precisely while considering expression levels difference and the interaction sites variation with bacteria envisaged the potential ability of buffalo LYZ protein with enhanced antibacterial effect. Thus, we speculated that the buffalo mammary glands expressed lysozyme has good antibacterial activity. This study on the buffalo lysozyme gene family not only provides comprehensive insights into the genetic architecture and their antibacterial effect but also offers a theoretical basis for the development of new veterinary drugs and animal health care for mastitis, as well as a new molecular genetic basis to study food or medical lysozyme.

Transcriptomic mechanisms of reduced PM2.5-Pb retention in the leaves of the low-Pb-accumulation genotype of Chinese cabbage.

Atmospheric fine particulate matter (PM2.5) mainly contributes to Pb accumulation in the edible leaves of Chinese cabbage in North China. It was found that a low-Pb-accumulation (LPA) genotype of Chinese cabbage contained less Pb in leaves than high-Pb-accumulation (HPA) genotype exposed to PM2.5-Pb. However, there are no data on the transcriptional regulatory mechanisms of foliar PM2.5-Pb uptake by Chinese cabbage. The present study investigated the retention of PM2.5-Pb in foliar apoplast and symplasm and the underlying molecular mechanisms of reduced Pb in LPA leaves. It appeared more Pb in apoplast and less Pb in symplasm of LPA leaves, whereas the pattern was opposite in HPA. There were 2646 and 3095 differentially expressed genes (DEGs) in LPA and HPA leaves under PM2.5-Pb stress with clearly genotype-specific function, respectively. Furthermore, mRNA levels of XTH16 regulating cell wall thickening, PME2 and PME6 involved in cell wall remodification were significantly expressed in LPA, but not in HPA. Meanwhile, foliar PM2.5-Pb stress downregulated expression of ZIP1, YSL1, and CNGC3 responsible for Pb influx to cell, and upregulated expression of ABCG36 regulated Pb efflux from symplasm in LPA leaves. These results improve our understanding to the mechanisms underlying foliar Pb uptake from PM2.5-Pb at transcriptomic level.

Rhizosphere bacteria regulated arsenic bioavailability and accumulation in the soil-Chinese cabbage system.

The accumulation of arsenic (As) in Chinese cabbage (Brassica rapa ssp. pekinensis) has recently been a source of concern for a potential risk to human health. It is unknown whether natural variations of As accumulation in different genotypes of Chinese cabbage are related to rhizobacterial characteristics. Experiments were conducted to investigate the mechanisms of rhizobacteria involving in As fates in a soil-Chinese cabbage system using various genotypes using high-throughput sequencing and quantitative PCR. There were significant differences in As accumulation in cabbage leaves between 32 genotypes, and genotypes of low-As-accumulation (LSA) and high-As-accumulation (HSA) were identified. The As concentrations in the shoots of LSA were 23.25 %, 24.19 %, 15.05 %, and 70.69 % lower than those of HSA in seedling stage (SS), rosette stage (RS), heading stage (HS), and mature stage (MS), respectively. Meanwhile, the relative abundances of phyla Patescibacteria (in RS), Acidobacteria and Rokubacteria (in HS) in the rhizosphere of LSA were 60.18 %, 28.19 %, and 45.38 % less than those of HSA, respectively. Additionally, both shoot-As and As translocation factor had significantly positive or negative correlations with the relative abundances of Rokubacteria or Actinobacteria. In LSA rhizosphere, the relative abundances of genera Flavobacterium (in SS), Ellin6055 and Sphingomonas (in HS) were 128.12 %, 83.69 % and 79.50 % higher than those of HSA, respectively. This demonstrated that rhizobacteria contribute to the accumulation and translocation of As in HSA and LSA. Furthermore, the gene copies of aioA and arsM in LSA rhizosphere were 25.54 % and 16.13 % higher than those of HSA, respectively, whereas the gene copies of arsC in LSA rhizosphere were 26.36 % less than those of HSA in MS, indicating that rhizobacteria are involved in As biotransformation in the soil. These results provide a comprehensive understanding of the relationship between characteristics of rhizobacterial communities and As variations in Chinese cabbage genotypes.

HPV-CCDC106 integration promotes cervical cancer progression by facilitating the high expression of CCDC106 after HPV E6 splicing.

Human papillomavirus (HPV) integration and high expression of HPV oncogenes (E6 and E7) are important mechanisms for HPV carcinogenesis in cervical cancer. However, the relationship between HPV integration and HPV E6 spliced transcripts, as well as the underlying mechanisms of HPV integration in carcinogenesis after HPV E6 splicing remains unclear. We analyzed HPV-coiled-coil domain containing 106 (CCDC106) integration samples to characterize the roles of HPV integration, E6 spliceosome I (E6*I), and high CCDC106 expression in cervical carcinogenesis. We found that E6 was alternatively spliced into the E6*I transcript in HPV-CCDC016 integration samples with low p53 expression, in contrast to the role of E6*I in preventing p53 degradation in cervical cancer cells. In addition, CCDC106 was highly expressed after HPV-CCDC106 integration, and interacted with p53, resulting in p53 degradation and cervical cancer cell progression in vitro and in vivo. Importantly, when E6*I was highly expressed in cervical cancer cells, overexpression of CCDC106 independently degraded p53 and promoted cervical cancer cell progression. In this study, we explored the underlying mechanisms of HPV-CCDC106 integration in HPV carcinogenesis after HPV E6 splicing, which should provide insight into host genome dysregulation in cervical carcinogenesis.

Daphnetin Alleviates Senile and Disuse Osteoporosis by Distinct Modulations of Bone Formation and Resorption.

Senile and disuse osteoporosis have distinct bone turnover status and lack effective treatments. In this study, senescence-accelerated mouse prone 8 (SAMP8) and hindlimb unloading mouse models were used to explore the protective effects of daphnetin on these two types of osteoporosis, and primary osteoblasts and bone marrow monocyte-derived osteoclasts, as well as pre-osteoblast MC3T3-E1, and osteoclast precursor RAW264.7 cells were used to investigate the underlying mechanisms. The results showed that daphnetin administration effectively improved bone remodeling in both senile and disuse osteoporosis, but with different mechanisms. In senile osteoporosis with low bone turnover, daphnetin inhibited NOX2-mediated ROS production in osteoblasts, resulting in accelerated osteogenic differentiation and bone formation, while in disuse osteoporosis with high bone turnover, daphnetin restored SIRT3 expression, maintained mitochondrial homeostasis, and additionally upregulated SOD2 to eliminate ROS in osteoclasts, resulting in attenuation of osteoclast differentiation and bone resorption. These findings illuminated that daphnetin has promising potential for the prevention and treatment of senile and disuse osteoporosis. The different mechanisms may provide clues and basis for targeted prevention and treatment of osteoporosis according to distinct bone turnover status.

Enhancing organic selenium content and antioxidant activities of soy sauce using nano-selenium during soybean soaking.

Nano-selenium has a greater potential than inorganic selenium in preventing selenium-deficiency diseases due to its higher safety. In this study, spherical nano-selenium particles (53.8 nm) were prepared using sodium selenite, ascorbic acid and chitosan. Selenium-enriched soy sauces were prepared by soaking soybean in nano-selenium and sodium selenite solutions (2-10 mg/L), respectively. Total selenium and organic selenium contents of soy sauces prepared by nano-selenium and sodium selenite were increased by 32-191-fold and 29-173-fold compared to the control (without selenium), and organic selenium accounted for over 90% of total selenium. Soy sauce prepared using 6 mg/L nano-selenium had the strongest antioxidant activities, which were 9.25-28.02% higher than the control. Nano-selenium (6 mg/L) markedly enhanced the koji's enzyme activities (9.76-33.59%), then the latter promoted the release of total phenolics (27.54%), total flavonoids (27.27%) and the formation of free amino acids (16.19%), Maillard reaction products (24.50%), finally the antioxidant activities of selenium-enriched soy sauce were enhanced.