Depression assessment using integrated multi-featured EEG bands deep neural network models: Leveraging ensemble learning techniques.

Mental Status Assessment (MSA) holds significant importance in psychiatry. In recent years, several studies have leveraged Electroencephalogram (EEG) technology to gauge an individual's mental state or level of depression. This study introduces a novel multi-tier ensemble learning approach to integrate multiple EEG bands for conducting mental state or depression assessments. Initially, the EEG signal is divided into eight sub-bands, and then a Long Short-Term Memory (LSTM)-based Deep Neural Network (DNN) model is trained for each band. Subsequently, the integration of multi-band EEG frequency models and the evaluation of mental state or depression level are facilitated through a two-tier ensemble learning approach based on Multiple Linear Regression (MLR). The authors conducted numerous experiments to validate the performance of the proposed method under different evaluation metrics. For clarity and conciseness, the research employs the simplest commercialized one-channel EEG sensor, positioned at FP1, to collect data from 57 subjects (49 depressed and 18 healthy subjects). The obtained results, including an accuracy of 0.897, F1-score of 0.921, precision of 0.935, negative predictive value of 0.829, recall of 0.908, specificity of 0.875, and AUC of 0.8917, provide evidence of the superior performance of the proposed method compared to other ensemble learning techniques. This method not only proves effective but also holds the potential to significantly enhance the accuracy of depression assessment.

Dual-signaling and ultrasensitive detection for PCT based on the photoelectric and electrocatalytic hydrogen evolution signals of Pt/Mo-CoFeS.

Few study has been carried out on the construction of immunesensors utilized the photoelectric and catalytic signal of nanomaterial. Here, a dual-signal electrochemical immunosensor was constructed for procalcitonin (PCT) detection based on the excellent photoelectric and hydrogen evolution performance of molybdenum-doped cobalt-iron sulfur nanosheets modified by platinum nanoparticles (Pt/Mo-CoFeS). Due to the electronic structure regulation between Pt and Mo-CoFeS, Pt/Mo-CoFeS exhibits superior photoelectric and hydrogen evolution performance compared to single Mo-CoFeS, which improved the sensitivity of the electrochemical immunosensor. Furthermore, the presence of Pt improves surface area and biocompatibility, achieving more antibodies loading and signal amplification. The linear range of PCT detection are 0.002-20 ng mL-1 and 0.002-50 ng mL-1, the detection limits are 0.0015 and 0.0012 ng mL-1. In addition, this electrochemical immunosensor was applied to the PCT analysis in human serum samples with high recoveries. F-test and t-test show that there is no significant difference in the test results between the HER and photoelectric signals, the mutual verification between above two signals can effectively improve the accuracy of detection result.

Diterpenoids from Euphorbia fischeriana with Kv1.3 Inhibitory Activity.

Euphorbia diterpenoids possess inhibitory effects of Kv1.3 ion channel, but most of this research has focused on diterpenoids with jatrophane-related or ingenane-related skeletons. In the present study, nine undescribed (1-9) and 16 known (10-25) diterpenoids, based on jatrophane, lathyrane, ingenane, abietane, and atisane skeletons, were identified from the methanol extract of the aerial parts of Euphorbia fischeriana. The structures were established by analysis of the spectroscopic data as well as by single-crystal X-ray diffraction analysis. Among the isolated diterpenoids, macrocyclic jatrophanes and lathyranes exerted Kv1.3 blocking activity. Compound 8 exhibited good selectivity on the inhibition of the Kv 1.3 channel rather than hERG channel, with a selectivity index over 7.0. The selective activity of lathyrane diterpenoids indicates that macrocyclic diterpenoids have the potential to be further investigated as therapeutic agents for the treatment of autoimmune diseases.

The specific DNA methylation landscape in focal cortical dysplasia ILAE type 3D.

Focal Cortical Dysplasia (FCD) is a frequent cause of drug-resistant focal epilepsy in children and young adults. The international FCD classifications of 2011 and 2022 have identified several clinico-pathological subtypes, either occurring isolated, i.e., FCD ILAE Type 1 or 2, or in association with a principal cortical lesion, i.e., FCD Type 3. Here, we addressed the DNA methylation signature of a previously described new subtype of FCD 3D occurring in the occipital lobe of very young children and microscopically defined by neuronal cell loss in cortical layer 4. We studied the DNA methylation profile using 850 K BeadChip arrays in a retrospective cohort of 104 patients with FCD 1 A, 2 A, 2B, 3D, TLE without FCD, and 16 postmortem specimens without neurological disorders as controls, operated in China or Germany. DNA was extracted from formalin-fixed paraffin-embedded tissue blocks with microscopically confirmed lesions, and DNA methylation profiles were bioinformatically analyzed with a recently developed deep learning algorithm. Our results revealed a distinct position of FCD 3D in the DNA methylation map of common FCD subtypes, also different from non-FCD epilepsy surgery controls or non-epileptic postmortem controls. Within the FCD 3D cohort, the DNA methylation signature separated three histopathology subtypes, i.e., glial scarring around porencephalic cysts, loss of layer 4, and Rasmussen encephalitis. Differential methylation in FCD 3D with loss of layer 4 mapped explicitly to biological pathways related to neurodegeneration, biogenesis of the extracellular matrix (ECM) components, axon guidance, and regulation of the actin cytoskeleton. Our data suggest that DNA methylation signatures in cortical malformations are not only of diagnostic value but also phenotypically relevant, providing the molecular underpinnings of structural and histopathological features associated with epilepsy. Further studies will be necessary to confirm these results and clarify their functional relevance and epileptogenic potential in these difficult-to-treat children.

Protective Effect of Astragaloside IV against Cadmium-Induced Damage on Mouse Renal Podocytes (MPC5).

In this study, we investigated the protective effect of Astragaloside IV (Ast) on mouse podocytes and its possible mechanism of action by constructing a cadmium-induced mouse renal podocytes model. We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 µM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 µM) was significantly reduced, while the death rate in the medium dose group (25 µM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.

Alteration of GABAergic neurons and abnormality of NKCC1/KCC2 in focal cortical dysplasia (FCD) type â ¡ lesions.

BACKGROUND: The current conclusions of molecular genetics still cannot satisfactorily explain the pathogenesis of focal cortical dysplasia (FCD) and the reason for drug resistance. The interneurons of GABA deserve attention. To observe the distribution and changes of GABAergic neurons and to explore the expression of cation chloride cotransporter NKCC1/KCC2 in focal cortical dysplasia (FCD) type II lesions is a highly significant job. METHODS: The expressions of GAD67(a marker of active GABAergic neuron), NKCC1 and KCC2 were detected by immunohistochemistry and immunohistochemistry double staining in 10 cases of FCD Ⅱa and 10 cases of FCD Ⅱb. The number of GAD67 positive neurons was counted, and the average absorbance (IA) of NKCC1 positive expression was measured, using Image Pro-Plus7.0 software. The data were statistically analyzed. RESULTS: The density of GABAergic neuron in focal dysplastic regions was significantly lower than that in the histologically "normal" cerebral cortex, regions from the same specimen (p < 0.0001, t-test). Compared to the NKCC1 staining intensity of neurons in the control group (measuring 1000 cells each), the IA value of dysmorphic neurons was significantly increased (p < 0.05, t'-test Cochran & Cox method). Intracytoplasmic concentration of KCC2 was evident in dysmorphic neurons but not in the other mature neurons. Most of the balloon cells were negative for NKCC1, except for few balloon cells showing sparse colored particles. The expression of KCC2 was negative in all balloon cells. CONCLUSIONS: The changes in the expression of NKCC1 and KCC2 may indicate that dysmorphic neurons were in a state similar to that of immature neurons. This state may be related to the abnormal electrophysiology of epilepsy. The difference between the number of GAD67 positive cells in the lesion site and the remote site of the same case may be an evaluation index of the effectiveness of surgery.

Whole Genome Resequencing Identifies Single-Nucleotide Polymorphism Markers of Growth and Reproduction Traits in Zhedong and Zi Crossbred Geese.

The broodiness traits of domestic geese are a bottleneck that prevents the rapid development of the goose industry. To reduce the broodiness of the Zhedong goose and thus improve it, this study hybridized it with the Zi goose, which has almost no broody behavior. Genome resequencing was performed for the purebred Zhedong goose, as well as the F2 and F3 hybrids. The results showed that the F1 hybrids displayed significant heterosis in growth traits, and their body weight was significantly greater than those of the other groups. The F2 hybrids showed significant heterosis in egg-laying traits, and the number of eggs laid was significantly greater than those of the other groups. A total of 7,979,421 single-nucleotide polymorphisms (SNPs) were obtained, and three SNPs were screened. Molecular docking results showed that SNP11 located in the gene NUDT9 altered the structure and affinity of the binding pocket. The results suggested that SNP11 is an SNP related to goose broodiness. In the future, we will use the cage breeding method to sample the same half-sib families to accurately identify SNP markers of growth and reproductive traits.

Reproductive Performance of Zi-Goose Promoted by Red Color Illumination.

The color of light affects the reproductive performance of poultry, but it is not clear what efficient illumination strategy could be adopted to improve the reproductive performance of Zi-goose. Red light can increase the average weekly egg production rate, egg production, and qualified production. It can increase the serum GnRH level and decrease the serum PRL, MT, and T4 levels. In our study, red light for 12 h increased the average weekly laying rate, average qualified egg production, and hatching rate of Zi-goose eggs, and increased the serum levels of FSH, LH, P4, E2, MT, T3, and T4. Blue light at 14 h improved the average weekly egg production rate, average egg production, and average qualified egg production, and reduce serum PRL and MT levels to ensure the improvement of reproductive performance of goose. A total of 705,714 overlapping group sequences, 471,145 transcript sequences, and 268,609 single gene sequences were obtained from 18 sequencing samples, with a total length of 323.04, 668.53, and 247.88 M, respectively. About 176,416 unigenes were annotated successfully in six databases, accounting for 65.68% of the total unigenes obtained. 2,106, 2,142, and 8,892 unigenes were identified in the hypothalamus, pituitary gland, and ovary of the birds respectively, with different expressions of light regulation. The hypothalamus, ovary, and pituitary were involved in 279, 327, and 275 KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathways in response to light, respectively. Through further significance analysis and differential discovery rate control, a total of five metabolic pathways were obtained which were closely related to the reproductive hormones of goose. Ten candidate genes related to the reproductive performance of goslings were selected according to the identification results of differentially expressed genes of goslings under red light and white light conditions and the genes involved in metabolic pathways significantly related to the reproductive hormones of goslings. The expression levels of GnRh-1 in the hypothalamus, GnRH-R, FSH ß and LH ß in the pituitary gland, and FSH-R and LH-R candidate genes in the ovary were higher under the 12 h red light treatment than white light. However, the expression levels of VIP, PRL, and PRL-R candidate genes in the hypothalamus, pituitary and ovary were lower under 12 h red light than under 12 h white light.

The effect of superfine grinding on physicochemical properties of three kinds of mushroom powder.

The effects of superfine grinding on apparent structure, physicochemical properties, and functional characteristics of three kinds of mushroom (Lentinus edodes, Hericium erinaceus, and Cordyceps militaris) powders were investigated. Coarse and 100-mesh powders of the mushrooms were prepared by common grinding, while a superfine powder was obtained by superfine grinding. By comparing the mushrooms before and after grinding, it was found that the mushroom fines did not produce new chemical groups but increased crystallinity. The results of the physicochemical properties revealed that the fines became less fluid after grinding. The protein content and solubility increased as the particle size decreased. The water and oil holding capacity, glucose binding capacity, cation exchange capacity, and antioxidant activity of the mushroom fines increased after grinding. This study provides a theoretical basis for the development process of edible mushroom food, as well as new ideas for the development of edible mushrooms.

IL-18/IL-18R Signaling Is Dispensable for ILC Development But Constrains the Growth of ILCP/ILCs.

Innate lymphoid cells (ILCs) develop from ILC progenitors in the bone marrow. Various ILC precursors (ILCPs) with different ILC subset lineage potentials have been identified based on the expression of cell surface markers and ILC-associated key transcription factor reporter genes. This study characterized an interleukin (IL)-7Rα+IL-18Rα+ ILC progenitor population in the mouse bone marrow with multi-ILC lineage potential on the clonal level. Single-cell gene expression analysis revealed the heterogeneity of this population and identified several subpopulations with specific ILC subset-biased gene expression profiles. The role of IL-18 signaling in the regulation of IL-18Rα+ ILC progenitors and ILC development was further investigated using Il18- and Il18r1-deficient mice, in vitro differentiation assay, and adoptive transfer model. IL-18/IL-18R-mediated signal was found to not be required for early stages of ILC development. While Il18r1-/- lymphoid progenitors were able to generate all ILC subsets in vitro and in vivo like the wild-type counterpart, increased IL-18 level, as often occurred during infection or under stress, suppressed the growth of ILCP/ILC in an IL-18Ra-dependent manner via inhibiting proliferation and inducing apoptosis.

The ILAE consensus classification of focal cortical dysplasia: An update proposed by an ad hoc task force of the ILAE diagnostic methods commission.

Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinico-pathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular-genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro-clinical-imaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico-pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and "no definite FCD on histopathology" as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi-layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options.

Antrodia cinnamomea and its compound dehydroeburicoic acid attenuate nonalcoholic fatty liver disease by upregulating ALDH2 activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disease, but currently has no specific medication in clinic. Antrodia cinnamomea (AC) is a medicinal fungus and it has been shown that AC can inhibit high fat diet (HFD)-induced lipid deposition in mouse livers, but the effective monomer in AC and mechanism against NAFLD remain unclear. It has been reported that aldehyde dehydrogenase 2 (ALDH2) activation shows protective effects on NAFLD. Our previous study demonstrates that AC and its monomer dehydroeburicoic acid (DEA) can upregulate the ALDH2 activity on alcoholic fatty liver disease mouse model, but it is not clear whether the anti-NAFLD effects of AC and DEA are mediated by ALDH2. AIM TO STUDY: To elucidate the active compound in AC against NAFLD, study whether ALDH2 mediates the anti-NAFLD effects of AC and its effective monomer. MATERIALS AND METHODS: WT mice, ALDH2-/- mice and ALDH2-/- mice re-expressed ALDH2 by lentivirus were fed with a methionine-choline deficient (MCD) diet or high fat diet (HFD) to induce NAFLD, and AC at the different doses (200 and/or 500 mg/kg body weight per day) was administrated by gavage at the same time. Primary hepatocytes derived from WT and ALDH2-/-mice were stimulated by oleic acid (OA) to induce lipid deposition, and the cells were treated with AC or DEA in the meantime. Lentivirus-mediated ALDH2-KD or ALDH2-OE were used to knock down or overexpress ALDH2 expression in HepG2 cells, respectively. Finally, the effects of DEA against NAFLD as well as its effects on upregulating liver ALDH2 and removing the harmful aldehyde 4-hydroxynonenal (4-HNE) were studied in the MCD diet-induced NAFLD mouse model. RESULTS: In WT mice fed with a MCD diet or HFD, AC administration reduced hepatic lipid accumulation, upregulated ALDH2 activity in mouse livers, decreased 4-HNE contents both in mouse livers and serum, inhibited lipogenesis, inflammation and oxidative stress and promoted fatty acid ß-oxidation. These effects were abolished in ALDH2 KO mice but could be restored by re-expression of ALDH2 by lentivirus. In primary hepatocytes of WT mice, AC and DEA inhibited OA-induced lipid accumulation and triglyceride (TG) synthesis, promoting the ß-oxidation of fatty acid in the meantime. However, these effects were lost in primary hepatocytes of ALDH2 KO mice. Moreover, the expression level of ALDH2 significantly affected the inhibitory effects of AC and DEA on OA-induced lipid deposition in HepG2 cells. The effects of AC and DEA on suppressing lipid deposition, inhibiting mitochondrial ROS levels, reducing TG synthesis, and promoting ß-oxidation of fatty acid were all enhanced with the overexpression of ALDH2 and reduced with the knockdown of ALDH2 expression. DEA showed dose-dependent effects on inhibiting liver lipid deposition, elevating ALDH2 activity and reducing 4-HNE levels in the livers of MCD diet-induced NAFLD mice. CONCLUSION: DEA is the effective compound in AC against NAFLD. The related anti-NAFLD mechanisms of AC and DEA were through upregulating ALDH2 expression and activity, thus enhancing the elimination of 4-HNE in the livers, and sequentially alleviating oxidative stress and inflammation, promoting fatty acid ß-oxidation and decreasing lipogenesis.

Application of Bone Marrow Mesenchymal Stem Cells Effectively Eliminates Endotoxemia to Protect Rat from Acute Liver Failure Induced by Thioacetamide.

BACKGROUND: Endotoxemia is related to worse clinical outcomes in acute liver failure (ALF), but its management remains unsatisfactory. In this study, we aimed to assess whether the application of bone marrow mesenchymal stem cells (BMSCs) could eliminate endotoxemia and protect rats against ALF induced by thioacetamide (TAA). METHODS: BMSCs were isolated from rats and identified by the specific morphology, differentiation potential, and surface markers. The optimal dose of TAA for this study was explored and TAA-induced ALF rats were randomized to three groups: the normal control group (Saline), ALF group (TAA + Saline), and BMSCs-treated group (TAA + BMSCs). The intestinal migration and differentiation of BMSCs was tracked in vivo, and intestinal permeability, endotoxin and inflammatory cytokines, histology, and mortality were analyzed. Moreover, we added the inhibitor of the PI3K/AKT/mTOR signaling pathway into the co-culture system of BMSCs with enterocytes and then performed CK and Villin expression experiments to assess the role of PI3K/AKT/mTOR signal pathway in the intestinal differentiation of BMSCs. RESULTS: BMSCs migrated to the intestinal injury sites and differentiated into enterocytes, intestinal permeability was decreased compared with the ALF group. The higher expression of endotoxin and inflammatory cytokines were reversed after BMSCs transplantation in rats with ALF. Mortality and intestinal lesion were significantly decreased. Blocking the PI3K/AKT/mTOR signal pathway inhibited BMSCs' intestinal differentiation in vitro. CONCLUSION: BMSCs can eliminate endotoxemia and reduce mortality in rats with ALF, and the PI3K/AKT/mTOR signal pathway is involved in intestinal differentiation. BMSCs transplantation could be a potential candidate for the treatment of endotoxemia in ALF.

Overweight/obesity-related transcriptomic signature as a correlate of clinical outcome, immune microenvironment, and treatment response in hepatocellular carcinoma.

Backgrounds: The pandemic of overweight and obesity (quantified by body mass index (BMI) ≥ 25) has rapidly raised the patient number of non-alcoholic fatty hepatocellular carcinoma (HCC), and several clinical trials have shown that BMI is associated with the prognosis of HCC. However, whether overweight/obesity is an independent prognostic factor is arguable, and the role of overweight/obesity-related metabolisms in the progression of HCC is scarcely known. Materials and methods: In the present study, clinical information, mRNA expression profile, and genomic data were downloaded from The Cancer Genome Atlas (TCGA) as a training cohort (TCGA-HCC) for the identification of overweight/obesity-related transcriptome. Machine learning and the Cox regression analysis were conducted for the construction of the overweight/obesity-associated gene (OAG) signature. The Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and the Cox regression analysis were performed to assess the prognostic value of the OAG signature, which was further validated in two independent retrospective cohorts from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). Subsequently, functional enrichment, genomic profiling, and tumor microenvironment (TME) evaluation were utilized to characterize biological activities associated with the OAG signature. GSE109211 and GSE104580 were retrieved to evaluate the underlying response of sorafenib and transcatheter arterial chemoembolization (TACE) treatment, respectively. The Genomics of Drug Sensitivity in Cancer (GDSC) database was employed for the evaluation of chemotherapeutic response. Results: Overweight/obesity-associated transcriptome was mainly involved in metabolic processes and noticeably and markedly correlated with prognosis and TME of HCC. Afterward, a novel established OAG signature (including 17 genes, namely, GAGE2D, PDE6A, GABRR1, DCAF8L1, DPYSL4, SLC6A3, MMP3, RIBC2, KCNH2, HTRA3, PDX1, ATHL1, PRTG, SHC4, C21orf29, SMIM32, and C1orf133) divided patients into high and low OAG score groups with distinct prognosis (median overall survival (OS): 24.87 vs. 83.51 months, p < 0.0001), and the values of area under ROC curve (AUC) in predicting 1-, 2-, 3-, and 4-year OS were 0.81, 0.80, 0.83, and 0.85, respectively. Moreover, the OAG score was independent of clinical features and also exhibited a good ability for prognosis prediction in the ICGC-LIHC-JP cohort and GSE54236 dataset. Expectedly, the OAG score was also highly correlated with metabolic processes, especially oxidative-related signaling pathways. Furthermore, abundant enrichment of chemokines, receptors, MHC molecules, and other immunomodulators as well as PD-L1/PD-1 expression among patients with high OAG scores indicated that they might have better responses to immunotherapy. However, probably exclusion of T cells from infiltrating tumors resulting in lower infiltration of effective T cells would restrict immunotherapeutic effects. In addition, the OAG score was significantly associated with the response of sorafenib and TACE treatment. Conclusions: Overall, this study comprehensively disclosed the relationship between BMI-guided transcriptome and HCC. Moreover, the OAG signature had the potential clinical applications in the future to promote clinical management and precision medicine of HCC.

Meta-analysis on the contents of trace elements in workers with occupational exposure to lead / 中华劳动卫生职业病杂志

Objective: To quantitatively evaluate the content differences of trace elements in workers with occupational exposure to lead. Methods: In January 2021, relevant literatures on the contents of trace elements in workers with occupational exposure to lead published from 1990 to 2020 were searched through CNKI, Wanfang, VIP, PubMed, web of science and Embase. Screened and extracted the literatures, and evaluated the quality of the included literatures with Newcastle Ottawa Scale. Meta analysis was performed with Review Manager 5.3 software, and standardized mean difference (SMD) and its 95% confidence interval were used as effect indicators. Results: A total of 20 literatures were included, and the quality scores were 5-7. The results of Meta-analysis showed that compared with the control group, the contents of blood zinc (SMD=-1.01, 95%CI: -1.53, -0.49) , hair zinc (SMD=-0.17, 95%CI: -0.33, -0.01) , hair copper (SMD=-0.50, 95%CI: -1.01, 0) , hair iron (SMD=-3.91, 95%CI: -5.80, -2.03) and hair manganese (SMD=-1.09, 95%CI: -2.02, -0.15) in occupational lead exposure group were significantly lower (P<0.05) . Compared with the control group, the content of cobalt in hair of occupational lead exposure group (SMD=1.41, 95%CI: 0.72, 2.10) was higher, and the difference was statistically significant (P<0.05) . There was no significant difference in the contents of blood chromium, blood copper, blood iron, blood manganese, blood selenium and hair nickel between the two groups (P>0.05) . Conclusion: Workers with occupational exposure to lead have abnormal trace elements.

5-Aza-2-deoxycytidine alleviates the progression of primary biliary cholangitis by suppressing the FoxP3 methylation and promoting the Treg/Th17 balance.

Primary biliary cholangitis (PBC) is a common autoimmune liver disease manifested by the infiltration of CD4+ T cells, and the subsequent targeted injury of biliary epithelial cells (BECs). As important components of CD4 subsets, the Treg/Th17 axis maintains an immunological balance between self-tolerance and inflammation in the liver microenvironment. However, the role and regulatory mechanism of the Treg/Th17 axis in PBC remain unclear. In this study, we examined the Treg/Th17 axis in PBC patients and found that the Treg/Th17 axis was imbalanced in PBC at both the transcriptional and cellular levels, with Treg being a weak candidate, which correlates with the PBC progression. This imbalanced Treg/Th17 axis was likely to be affected by the FoxP3 hypermethylation, which was related to the increase of DNA methyltransferase. Furthermore, the effect of 5-Aza-2-deoxycytidine (DAC)-mediated FoxP3 demethylation on PBC mice was investigated. We verified that DAC significantly suppressed the FoxP3 methylation and rebuilt the Treg/Th17 balance, resulting in the alleviation of liver lesions and inflammation. Taken together, our data indicate that DAC plays a positive role in alleviating the progression of PBC through the inhibition of DNA methylation of FoxP3 to rebuild the balanced Treg/Th17 axis. DAC could be considered as a potential candidate for the development of new anti-inflammation strategies in the treatment of PBC.

Role of Removed Lymph Nodes on the Prognosis of M0 Small-Bowel Neuroendocrine Tumors: a Propensity Score Matching Analysis from SEER Database.

BACKGROUND: Current studies on the number of removed lymph nodes (LNs) and their prognostic value in small-bowel neuroendocrine tumors (SBNETs) are limited. This study aimed to clarify the prognostic value of removed LNs for SBNETs. METHODS: SBNET patients without distant metastasis from 2004 to 2017 in the SEER database were included. The optimal cutoff values of examined LNs (ELNs) and negative LNs (NLNs) were calculated by the X-tile software. Propensity score matching (PSM) was done to match patients 1:1 on clinicopathological characteristics between the two groups. The Kaplan-Meier method with log-rank test and multivariable Cox proportional-hazards regression model were used to evaluate the prognostic effect of removed LNs. RESULTS: The cutoff values of 14 for ELNs and 9 for NLNs could well distinguish patients with different prognoses. After 1:1 PSM, the differences in clinicopathological characteristics between the two groups were significantly reduced (all P > 0.05). Removal of more than one LN significantly improved the prognosis of the patients (P < 0.001). The number of lymphatic metastasis in the sufficiently radical resection group (SRR, 3.74 ± 3.278, ELN > 14 and NLN > 9) was significantly more than that in the insufficiently radical resection group (ISRR, 2.72 ± 3.19, ELN < 14 or NLN < 9). The 10-year overall survival (OS) of the SRR was significantly better than that of the ISRR (HR = 1.65, P = 0.001, 95% CI: 1.24-2.19). CONCLUSION: Both ELNs and NLNs can well predict the OS of patients. Systematic removal of more than 14 LNs and more than 9 NLNs can increase the OS of SBNET patients.

Critical prognostic value of the log odds of negative lymph nodes/tumor size in rectal cancer patients.

BACKGROUND: The number of negative lymph nodes (NLNs) and tumor size are associated with prognosis in rectal cancer patients undergoing surgical resection. However, little is known about the prognostic significance of the NLN count after adjusting for tumor size. AIM: To assess the prognostic impact of the log odds of NLN/tumor size (LONS) in rectal cancer patients. METHODS: Data of patients with stage I-III rectal cancer were extracted from the Surveillance, Epidemiology, and End Results Program database. These patients were randomly divided into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of the LONS. The optimal cutoff values of LONS were calculated using the "X-tile" program. Stratified analysis of the effect of LONS on cancer-specific survival (CSS) and overall survival (OS) were performed. The Kaplan-Meier method with the log-rank test was used to plot the survival curve and compare the survival data among the different groups. RESULTS: In all, 41080 patients who met the inclusion criteria were randomly divided into a training cohort (n = 28775, 70%) and a validation cohort (n = 12325, 30%). Univariate and multivariate analyses identified the continuous variable LONS as an independent prognostic factor for CSS [training cohort: Hazard ratio (HR) = 0.47, 95% confidence interval (CI): 0.44-0.51, P < 0.001; validation cohort: HR = 0.46, 95%CI: 0.41-0.52, P < 0.001] and OS (training cohort: HR = 0.53, 95%CI: 0.49-0.56, P < 0.001; validation cohort: HR = 0.52, 95%CI: 0.42-0.52, P < 0.001). The X-tile program indicated that the difference in CSS was the most significant for LONS of -0.8, and the cutoff value of -0.4 can further distinguish patients with a better prognosis in the high LONS group. Stratified analysis of the effect of the categorical variable LONS on CSS and OS revealed that LONS was also an independent predictor, independent of pN stage, pT stage, tumor-node-metastasis stage, site, age, sex, the number of examined lymph nodes, race, preoperative radiotherapy and carcinoembryonic antigen level. CONCLUSION: LONS is associated with improved survival of rectal cancer patients independent of other clinicopathological factors.

Comparison of the bacteriostatic effects of quaternary ammonium compounds and their combinations on a dairy farm environment and the microbial contamination of dairy products.

Disinfection is key for controlling microbial contamination and ensuring the safe production of milk and dairy products. In this study, we developed a new disinfection method using quaternary ammonium surfactant N-dodecyl-2-(pyridin-1-yl) acetamide chloride as the main component to form a bactericidal complex with either chlorhexidine acetate or glutaraldehyde, and we evaluated the bactericidal effects, safety, and clinical application value of the compound disinfectants. An in vivo acute oral toxicity assay in mice showed an LD50 > 5000 mg/kg body weight without abnormality in pathological tissue sections. Comparison with commercially available products also showed that they have outstanding bactericidal effects. Clinical trials proved that the compound disinfectants have excellent bactericidal effects on the air and ground of the dairy farm and on the skin of cattle, especially in a dairy farm environment. Our findings confirm that the new compound disinfectants have excellent bactericidal performance and are safe to use as disinfectants to prevent mastitis and contamination of the cattle farm environment.

La désinfection est essentielle pour maitriser la contamination microbienne et garantir une production sécuritaire de lait et de produits laitiers. Dans cette étude, nous avons développé une nouvelle méthode de désinfection utilisant l'ammonium quaternaire tensioactif d'acétamide de chlorure de N-dodécyl-2-(pyridin-1-yl) comme composant principal pour former un complexe bactéricide avec l'acétate de chlorhexidine ou le glutaraldéhyde, et nous avons évalué les effets bactéricides, la sécurité et la valeur d'application clinique des désinfectants composés. Un test de toxicité orale aiguë in vivo chez la souris a montré une DL50 > 5000 mg/kg de poids corporel sans anomalie pathologique dans les sections de tissus. La comparaison avec les produits disponibles dans le commerce a également montré qu'ils ont des effets bactéricides remarquables. Des essais cliniques ont démontré que les désinfectants composés ont d'excellents effets bactéricides sur l'air et le sol de la ferme laitière et sur la peau des bovins, en particulier dans un environnement de ferme laitière. Nos résultats confirment que les nouveaux désinfectants composés ont d'excellentes performances bactéricides et sont sécuritaires à utiliser comme désinfectants pour prévenir la mammite et la contamination de l'environnement de l'élevage bovin.(Traduit par Docteur Serge Messier).