The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study.

Hepatic encephalopathy (HE) is a central nervous system dysfunction syndrome caused by acute and chronic liver failure or various portal systemic shunt disorders. HE arises from metabolic disorder and excludes other known types of encephalopathy. HE is a major cause of death in people with liver disease. Early diagnosis and timely treatment are key to improving HE prognosis. Herein, we established a model of HE and performed metabolomics to identify 50 significantly differential metabolites between the HE group and control group. The main metabolic pathways associated with these differential metabolites were the purine metabolism, pyrimidine metabolism, aminoacyl tRNA biosynthesis, and glucose metabolism. Through proteomics analysis, we identified 226 significantly differential proteins (52 up-regulated and 174 down-regulated). The main (Kyoto Encyclopedia of Genes and Genomes) enrichment pathways were the Staphylococcus aureus infection, vitamin digestion and absorption, and complement and coagulation cascades. Through the conjoint analysis of proteomics and metabolomics, the differentially present proteins and metabolites were found to be involved in vitamin digestion and absorption, and ferroptosis pathways. In HE, malondialdehyde was significantly elevated, but glutathione was significantly diminished, and the redox balance was destroyed, thus leading to changes in proteins' levels associated with the ferroptosis pathway. In conclusion, this study preliminarily explored the molecular and metabolic mechanisms underlying HE.

Clinical and prognosis value of the number of metastatic lymph nodes in patients with papillary thyroid carcinoma.

OBJECTIVE: It has been reported that papillary thyroid carcinoma (PTC) patients with lymph node metastasis (LNM) are largely associated with adverse outcomes. The present study aimed to assess the correlation between the number of metastatic lymph nodes (NMLNs) and clinical prognosis in patients with PTC. METHODS: We retrospectively reviewed the medical records of patients with PTC who underwent initial thyroid cancer surgery in Renmin Hospital of Wuhan University between 2017 and 2019. A total of 694 patients with PTC and cervical lymph node dissection as well as a total checked number of lymph nodes ≥ 5 were involved in this study. The clinicopathological characteristics of patients were compared according to NMLNs, the number of central cervical lymph nodes (CLNs) and the number of lateral lymph nodes (LLNs). RESULTS: NMLNs > 5, CLNs > 5 and LLNs > 5 were 222 (32.0%), 159 (24.3%) and 70 (10.1%) seen in the analyzed samples, respectively. Young patients, patients with larger tumor diameter, bilaterality, multifocality and gross extrathyroidal extension (ETE) were more inclined to NMLNs > 5, CLNs > 5 and LLNs > 5 (P < 0.05). It was found that the recurrence-free survival among pN1 patients was significantly discrepant between different groups (NMLNs ≤ 5/5: P = 0.001; LLNs ≤ 5/5: P < 0.001). In multivariate logistic regression analysis, patients aged < 55 years (OR = 1.917), primary tumor size > 10 mm (OR = 2.131), bilaterality (OR = 1.889) and tumor gross ETE (OR = 2.759) were independent predictors for high prevalence of total NMLNs > 5 (P < 0.05). Specially, patients aged < 55 years (OR = 2.864), primary tumor size > 10 mm (OR = 2.006), and tumor gross ETE (OR = 2.520) were independent predictors for high prevalence of CLNs > 5 (P < 0.01); Bilaterality (OR = 2.119), CLNs > 5 (OR = 6.733) and tumor gross ETE (OR = 4.737) were independent predictors for high prevalence of LLNs > 5 (P < 0.05). CONCLUSIONS: In conclusion, it is evident that NMLNs is related to the invasive clinicopathological features and adverse outcome of patients with PTC which should be correctly evaluated to provide an appropriate guidance for reasonable treatment and careful follow-up.

The role of C/EBP homologous protein (CHOP) in regulating macrophage polarization in RAW264.7 cells.

Schistosomiasis is a zoonotic parasitic disease that is endemic in Asia. Macrophages are mainly involved in the inflammatory response of late schistosoma infection. Our previous study found that C/EBP homologous protein (CHOP) expression is significantly increased, and M2 macrophages are activated in schistosome-induced liver fibrosis mice. However, the role of CHOP in the regulation of macrophage polarization remains to be further studied. Western blotting or quantitative PCR revealed that IL-4 increased the expression of arginase-1, macrophage mannose receptor 1, phosphorylation signal transducer and activator of transcription 6 (p-STAT6), Krüppel-like factor 4 (KLF4), CHOP, and IL-13 receptor alpha (IL-13Rα) and induced M2 polarization in RAW264.7 as measured by flow cytometry. Inhibiting STAT6 phosphorylation (AS1517499) reduced the IL-4-induced expression of KLF4, CHOP, and IL-13Rα and also the number of M2 macrophages. The overexpression of CHOP stimulated M2 polarization, but AS1517499 inhibited this effect. CHOP increased the protein expression of KLF4 but did not change the expression of p-STAT6. Soluble egg antigen (SEA) could promote the IL-4-induced protein expression of p-STAT6, CHOP, and KLF4. Overall, the findings show that SEA can promote the activation of M2 macrophages by causing increased CHOP-induced KLF4 levels and activation of STAT6 phosphorylation.

Citrobacter freundii causing Ginger (Zingiber officinale Rosc.) Rot in Tangshan, China.

Ginger (Zingiber officinale Rosc.) is an important economic crop and its rhizome can be used as seasoning agent and traditional medicine in China. During July 2018 and 2019, decay symptoms occurred in the ginger planting area of Tangshan City, Hebei Province, with incidence rates of 15%～20%. The pathogen infected the rhizomes and leaves. The symptoms included leaves chlorosis and gradually wilting, even the whole plant wilted, the rhizome became soft and presented light brown maceration. In serious cases, the interior of rhizome was completely eroded, gray-white juice overflowing the epidermis, and with foul smell. The rhizome surfaces of ginger plants were disinfected with 1% NaOCl, and colonies were isolated and purified on nutrient agar (NA) solid medium by streaking. Eight isolates were obtained from 15 diseased tissue samples. Further morphological, physiological and biochemical identification of the pure cultured bacteria were carried out. Three strains of bacteria were picked for further analysis. All of the three strains were gram-negative, short rod-shaped，nonmotile bacillus. Colonies were round and milky yellow, smooth raised, and moist after incubation at 28°C for 24h on NA. Physiological and biochemical test results showed that strains were facultatively anaerobic, negative for indole, methyl red, the Voges-Prauskauer test (V-P) and urease; positive for glucose, sucrose, sorbitol, inositol, mannitol, citrate utilization and hydrogen sulfide production; gelatin liquefaction. A typical hypersensitive reaction was induced on 12-week-old tobacco (Nicotiana benthamiana) leaves, which were inoculated by injecting suspensions of the isolated strain (108 CFU/mL) at 25 ℃ after 24h. These characteristics were consistent with Citrobacter freundii (Werkman and Gillen 1932). To further assess the identity of the strains, the genomic DNA was extracted from one bacterium（JXJ4）. The partial 16S rRNA region (Lane 1991) and specific rpoB and gyrB genes (Mollet et al. 1997, Brady et al. 2013) were amplified and sequenced with primers 27F/1492R, CM7/CM31b and UP1f/UP2r, respectively. The obtained 16S, rpoB and gyrB sequences (GenBank accession MN148645, MN158728 and MW199734) of the isolate showed 99.93%, 99.51% and 99.82% identity to the corresponding sequences of C. freundii in GenBank (CP024679.1, CP024677.1 and KM509081.1). Maximum likelihood analysis was performed, and the phylogenetic tree clustered with C. freundii (MEGAX, Bootstrap n=1000). The pathogenicity of the isolates was tested on ginger plants and rhizomes tissue. The bacterial suspensions (108 CFU/mL) of three isolates were injected into the basal stem and rhizomes center of 9 healthy ginger seedlings respectively, and Control groups were treated with sterile water. The inoculated plants were kept in a moist chamber (28°C, 16-h light and 8-h dark period) and ginger rhizomes were placed in the incubator (30°C, 16-h light and 8-h dark period). Seven days after inoculation, the ginger tubers showed symptoms of decay, and 20 to 25 days later, the ginger plant leaves browned and died. The pathogenicity test was repeated 4 times and all controls were healthy. Pathogens were reisolated from symptomatic plants and rhizomes and identified as C. freundii based on the morphological, biochemical and molecular methods described previously, fulfilling Koch's hypothesis. To our knowledge, this is the first report of ginger rot caused by C. freundii in China.

First Report of Colletotrichum cereale Causing Anthracnose on Avena nuda in China.

Naked oats (Avena nuda L.) is rich in protein, fat, vitamin, mineral elements and so on, and is one of the world's recognized cereal crops with the highest nutritional and healthcare value. In July 2019, leaf spot was detected on A. nuda in Zhangbei experimental station of Hebei Agricultural University. The incidence of disease is 10% to 20%. The symptoms were similar to anthracnose disease, the infected leaves had fusiform or nearly fusiform yellowish-brown spots, yellow halo around the spots. Numerous acervuli with black setae diagnostic of fungi in the genus Colletotrichum were present on necrotic lesions. To identify the pathogen, ten symptomatic leaves were collected, and only one disease spot was isolated from each leaf. Small square leaf pieces (3 to 5 mm) were excised from the junction of diseased and healthy tissues with a sterile scalpel and surface disinfested with 75% alcohol for 30s, 0.1% corrosive sublimate for 1 min, rinsed three times in sterile water. Plant tissues were then transferred on potato dextrose agar (PDA), and incubated at 25°C for 7 days. Two fungal isolates were obtained and purified by single-spore isolation method. All fungi have the same morphology and no other fungi were isolated. The aerial mycelium was gray black. The conidia were colorless and transparent, falcate, slightly curved, tapered toward the tips, and produced in acervuli with brown setae. The length and width of 100 conidia were measured and size ranged from 1.86 to 3.84 × 8.62 to 29.81 µm. These morphological characteristics were consistent with the description of Colletotrichum cereale (Crouch et al. 2006). To further assess the identity of the species, the genomic DNA of two fungal isolates (LYM19-4 and LYM19-10) was extracted by a CTAB protocol. The ribosomal DNA internal transcribed spacer (ITS) region as well as, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), and the beta-tubulin 2 (Tub2) partial genes were amplified and sequenced with primers ITS4/5, GDF/GDR, ACT-512F/ACT-783R, and T1/Bt2b, respectively (Carbone et al. 1999; Templeton et al. 1992; O'Donnell et al. 1997; Glass et al. 1995). The sequences of the ITS-rDNA region (MW040121, MW040122), the GAPDH sequences (MW052554, MW052555), the ACT sequences (MW052556, MW052551) and the Tub2 sequences (MW052552, MW052553) of the two single-spore isolates were more than 99% identical to C. cereale isolate CGMCC3.15110 (JX625159, KC843517, KC843534 and JX625186). Maximum likelihood tree based on concatenated sequences of the four genes were constructed using MEGA7. The results showed the strains isolated from A. nuda were closely related to C. cereale, as supported by high bootstrap values. A pathogenicity test of the C. cereale isolates was performed on first unfolding leaves of A. nuda. Koch's postulates were carried out with isolates by spraying a conidial suspension of 106 conidia/mL on leaves of healthy A. nuda. Four replicated pots were inoculated at a time, 10 leaves each pot, while sterile distilled water was used as the control. All treated plants were placed in a moist chamber (25°C, 16-h light and 8-h dark period). Anthracnose symptoms developed on the inoculated plants 7 days post inoculation while all control plants remained healthy. Microscopic examination showed the surface of infected leaves had the same acervuli, setae, and conidia as the original isolate. The pathogenicity test was repeated three times. C. cereale was previously reported as the causal agent of anthracnose on feather reed grass in US (Crouch et al. 2009). To our knowledge, this is the first report of C. cereale as the causal agent of A. nuda anthracnose in China.

First Report of Alternaria alternata Causing Leaf Spot on Avena nuda in Zhangbei, China.

Naked oats (Avena nuda L.) is an independent species of Avena, which can be used as both food and forage for rich nutritional value. In August 2019, leaf spot was observed at a naked oats planting base in Zhangbei County, Zhangjiakou City, Hebei Province. The incidence of disease was 40% to 50%. The symptoms of the lesions were chlorosis and gradually developing light brown spots with light yellow halos. The spots were irregular, enlarged and even coalesced to form large areas of necrosis on leaves. To identify the pathogen, twenty symptomatic leaves were collected, and one disease spot was isolated from each samples. Small square leaf pieces (3 to 5 mm) were excised from the junction of diseased and healthy tissues with a sterile scalpel and were sterilized with 75% alcohol for 30s, 0.1% mercuric chloride solution for 1 min, and then rinsed three times with sterile water, then transferred cultured on potato dextrose agar (PDA) at 25°C for 7 days. Four fungal isolates were obtained and purified by single-spore isolation method. All fungi have the same morphology and no other fungi were isolated. Colonies of the isolates had round margins, and thick fluffy aerial mycelia with brown coloration after 7 days on PDA. Conidiophores were brown, straight or flexuous, septate, single or in clusters. Conidia were obclavate or oval, dark brown, and size ranging from 4.61 to 15.68 × 6.61 to 35.49µm (n=100), with longitudinal and transverse septa varying from 1 to 3 and 1 to 7, respectively. The transverse median septum of the central section was especially thick. On the basis of morphological characteristics, the isolates were identified as Alternaria spp. (Simmons 2007). To further assess the identity of the species, the genomic DNA of pathogenic isolate (YM3) was extracted by CTAB protocol. The ribosomal DNA internal transcribed spacer (ITS) region, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the RNA polymerase II second largest subunit (RPB2), and the plasma membrane ATPase genes were amplified and sequenced with primers ITS1/4, gpd1/2, RPB2-6F/7cR and ATPDF1/ATPDR1 respectively (Nishikawa and Nakashima 2015; Woudenberg et al. 2015). Sequences of ITS, GAPDH, RPB2 and ATPase (MN646900, MT233043, MT233042, MN640794) of the isolate was 99.82%, 99.68%, 100% and 99.51% similar to the fungus A. alternata (MK461082.1, MK451978, KP124770.1, MK804115). A neighbor-joining phylogenetic tree was constructed by combining all sequenced loci in MEGA7. The isolate YM3 clustered in the A. alternata clade with 100% bootstrap support. Therefore, the pathogen was identified as A. alternata based on the morphological characteristics and molecular identification. A pathogenicity test of the A. alternata isolates was performed by placing mycelial disks (5 mm) with conidia on the surface of the first unfolding leaves of naked oats. Each leaf was inoculated with three disks. The pathogenicity test was repeated four times, and 10 leaves were inoculated in each repetition, while sterile PDA was used as the control. All treated plants were placed in a moist chamber (25°C, 16-h light and 8-h dark period). Leaf spot symptoms developed on the inoculated plants about 10 days post inoculation while all control plants remained healthy. The similar isolates were re-isolated from the inoculated and infected leaves and identified as A. alternata by DNA sequencing, fulfilling Koch's postulates. It has been reported that A. alternata can cause leaf spots on A. Sativa(Chen et al. 2020). However, to our knowledge, this is the first report of A. alternata causing leaf spots on A. nuda in China. It can be concluded that A. alternata can cause leaf spot disease of oats (A. Sativa and A. nuda). The spots disease is worthy of our attention for its harm to the production of oats.

Race and Virulence Analysis of Puccinia triticina in China in 2014 and 2015.

Wheat leaf rust, caused by Puccinia triticina, is an important fungal disease of wheat in China. To study races of the pathogen in China, leaf rust samples were collected from 14 provinces in 2014 and 15 provinces in 2015. From the samples, 494 single-uredinial isolates were derived from the 2014 collection and 649 from the 2015 collection. These isolates were tested on 40 near-isogenic lines of Thatcher carrying single leaf rust resistance genes. From the isolates, 84 races were identified in 2014 and 65 races in 2015. Races THTT (22.1%), THTS (19.6%), THJT (8.7%), PHTT (4.9%), and PHJT (3.6%) were the most common races in 2014, and THTT (28.4%), THTS (12.8%), THJT (11.6%), THJS (9.9%), and PHTT (9.7%) were the most frequent in 2015. All of these races were avirulent to resistance genes Lr9 and Lr24. THTT and THTS, the most frequent races in both years, were widely distributed throughout the country. The frequencies of isolates with virulence to Lr1, Lr2a, Lr2c, Lr3, Lr16, Lr26, Lr11, Lr17, LrB, Lr10, Lr14a, Lr2b, Lr3bg, Lr14b, Lr32, Lr33, and Lr50 were over 80%, whereas the frequencies of virulence to Lr9, Lr19, Lr25, Lr28, Lr29, and Lr47 were less than 3.5%. In the present study, all isolates were avirulent to Lr24 and Lr38. The race analysis and individual virulence frequencies provide guidance to breeders in choosing leaf rust resistance genes for use in breeding programs.

A new diterpenoid from the leaves of Platycladus orientalis.

A new diterpenoid, 17-methyl-8, 13-labdadien-15, 16-olid-19-oic acid methyl ester (1), along with two known compounds 2 and 3, were isolated from the leaves of Platycladus orientalis (L.) Franco. The structures were confirmed based on the analysis of HR-MS, 1D-NMR, and 2D-NMR spectra and the configuration of 1 was confirmed by the single-crystal X-ray diffraction.

Polychlorinated Biphenyl Quinone Metabolite Promotes p53-Dependent DNA Damage Checkpoint Activation, S-Phase Cycle Arrest and Extrinsic Apoptosis in Human Liver Hepatocellular Carcinoma HepG2 Cells.

Polychlorinated biphenyls (PCBs) are a group of persistent organic pollutants. The toxic behavior and mechanism of PCBs individuals and congeners have been extensively investigated. However, there is only limited information on their metabolites. Our previous studies have shown that a synthetic PCB metabolite, PCB29-pQ, causes oxidative damage with the evidence of cytotoxicity, genotoxicity, and mitochondrial-derived intrinsic apoptosis. Here, we investigate the effects of PCB29-pQ on DNA damage checkpoint activation, cell cycle arrest, and death receptor-related extrinsic apoptosis in human liver hepatocellular carcinoma HepG2 cells. Our results illustrate that PCB29-pQ increases the S-phase cell population by down-regulating cyclins A/D1/E, cyclin-dependent kinases (CDK 2/4/6), and cell division cycle 25A (CDC25A) and up-regulating p21/p27 protein expressions. PCB29-pQ also induces apoptosis via the up-regulation of Fas/FasL and the activation of caspase 8/3. Moreover, p53 plays a pivotal role in PCB29-pQ-induced cell cycle arrest and apoptosis via the activation of ATM/Chk2 and ATR/Chk1 checkpoints. Cell cycle arrest and apoptotic cell death were attenuated by the pretreatment with antioxidant N-acetyl-cysteine (NAC). Taken together, these results demonstrate that PCB29-pQ induces oxidative stress and promotes p53-dependent DNA damage checkpoint activation, S-phase cycle arrest, and extrinsic apoptosis in HepG2 cells.

Polychlorinated biphenyl quinone induces mitochondrial-mediated and caspase-dependent apoptosis in HepG2 cells.

Polychlorinated biphenyl (PCB) quinones are known to cause toxic effects, but their mechanisms are quite unclear. In this study, we examined whether 2,3,5-trichloro-6-phenyl-[1,4]benzoquinone, PCB29-pQ, induces cell death via apoptosis pathway. Our result showed PCB29-pQ exposure decreased HepG2 cell viability in a time-dependent manner. Lactate dehydrogenase leakage assay also implied the cytotoxicity of PCB29-pQ. 4',6-Diamidino-2-phenylindole dihydrochloride staining and flow cytometry assays both confirmed PCB29-pQ caused dose-dependent apoptotic cell death in HepG2 cells. Furthermore, we found that PCB29-pQ exposure increased cellular reactive oxygen species (ROS) level, decreased mitochondrial membrane potential and induced the translocation of cytochrome c from mitochondria into cytosol in HepG2 cells. Moreover, PCB29-pQ exposure induced B-cell lymphoma 2 (Bcl-2) downregulation and Bcl-2-associated X (Bax) upregulation, poly(ADP-ribose) polymerase cleavage, accompanied with the increased caspase-3/9 and p53 expressions. Taking together, these results suggested PCB29-pQ induced HepG2 cells apoptosis through a ROS-driven, mitochondrial-mediated and caspase-dependent pathway.

Protective effects of lipoic acid and mesna on cyclophosphamide-induced haemorrhagic cystitis in mice.

The protective roles of lipoic acid (LA)/vitamin C (VC) and mesna on preventing cyclophosphamide (CYP)-induced haemorrhagic cystitis (HC) were investigated. Swiss mice were divided into five groups randomly. HC was induced by a single dose of CYP injection (150-mg kg(-1) bodyweight). Group I was injected with saline (four times in total) throughout as control group. Group II received CYP and three equal doses of saline. Group III received CYP and three doses of mesna, whereas Group IV (or Group V) received CYP, mesna + two doses of VC (or LA). All injections were performed intraperitoneally. After 24 h of cystitis induction, the bladders were collected for all the experiments. Histological characterization showed that CYP injection resulted in severe HC. Reactive oxygen species (ROS) and thiobarbituric acid reactive substances' levels were increased in CYP group. The activities of antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase, were inhibited significantly in CYP groups, respectively. In addition, activation of c-jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in the mechanism of CYP-induced HC but not extracellular signal regulated kinases (ERK). Significant suppression of p38 phosphorylation on Group V suggests that LA and mesna may have synergistic beneficial effect. In Groups III-V, all the parameters of HC and oxidative stress were inhibited significantly. Taking together, we found that these results illustrated that ROS play an important role on CYP-induced HC and the administration of LA/VC with mesna may have therapeutic potential against CYP-induced bladder HC.

Application of fused graphical lasso to statistical inference for multiple sparse precision matrices.

In this paper, the fused graphical lasso (FGL) method is used to estimate multiple precision matrices from multiple populations simultaneously. The lasso penalty in the FGL model is a restraint on sparsity of precision matrices, and a moderate penalty on the two precision matrices from distinct groups restrains the similar structure across multiple groups. In high-dimensional settings, an oracle inequality is provided for FGL estimators, which is necessary to establish the central limit law. We not only focus on point estimation of a precision matrix, but also work on hypothesis testing for a linear combination of the entries of multiple precision matrices. We apply a de-biasing technology, which is used to obtain a new consistent estimator with known distribution for implementing the statistical inference, and extend the statistical inference problem to multiple populations. The corresponding de-biasing FGL estimator and its asymptotic theory are provided. A simulation study and an application of the diffuse large B-cell lymphoma data show that the proposed test works well in high-dimensional situation.

Association of thyroid autoimmunity with extra-thyroid diseases and the risk of mortality among adults: evidence from the NHANES.

Background: Thyroid autoimmunity is one of the most prevalent autoimmune diseases. However, its association with extra-thyroid diseases and mortality risk in the general population remains uncertain. Our study aims to evaluate the association of thyroid autoimmunity with extra-thyroid disease and the risk of mortality. Methods: A prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) with participants from 2007-2008, 2009-2010, and 2011-2012, tracking their mortality until 2019. Associations between thyroid autoimmunity, which was defined as having positive thyroid peroxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb), and extra-thyroid disease including diabetes, hypertension, cardiovascular disease, chronic lung disease, arthritis, cancer and chronic renal disease and the risk of mortality were investigated. Results: A total of 7431 participants were included in this study. Positive The prevalence of positive TgAb was 7.54%, and positive TPOAb prevalence was 11.48%. TgAb was significantly associated with diabetes (Model 1: OR=1.64, 95% CI:1.08-2.50; Model 2: OR=1.93, 95% CI: 1.21-3.08) and hypertension (Model 1: OR=0.67, 95% CI: 0.49-0.91; Model 2: OR=0.62, 95% CI: 0.44-0.88). TPOAb was associated with a lower prevalence of chronic lung disease (model 1: OR=0.71, 95% CI: 0.54-0.95; model 2: OR=0.71, 95% CI: 0.53-0.95). No associations were observed between TgAb, TPOAb and other extra-thyroid diseases. Neither TgAb nor TPOAb were associated with all-cause mortality or heart disease mortality. Conclusion: TgAb was linked to a higher prevalence of diabetes and a lower prevalence of hypertension, while TPOAb was associated with a decreased prevalence of chronic lung disease. However, neither TgAb nor TPOAb posed a risk for all-cause mortality or heart disease mortality.

Metabolic syndrome and thyroid Cancer: risk, prognosis, and mechanism.

The increasing incidence of thyroid cancer (TC) cannot be fully explained by overdiagnosis. Metabolic syndrome (Met S) is highly prevalent due to the modern lifestyle, which can lead to the development of tumors. This review expounds on the relationship between Met S and TC risk, prognosis and its possible biological mechanism. Met S and its components were associated with an increased risk and aggressiveness of TC, and there were gender differences in most studies. Abnormal metabolism places the body in a state of chronic inflammation for a long time, and thyroid-stimulating hormones may initiate tumorigenesis. Insulin resistance has a central role assisted by adipokines, angiotensin II, and estrogen. Together, these factors contribute to the progression of TC. Therefore, direct predictors of metabolic disorders (e.g., central obesity, insulin resistance and apolipoprotein levels) are expected to become new markers for diagnosis and prognosis. cAMP, insulin-like growth factor axis, angiotensin II, and AMPK-related signaling pathways could provide new targets for TC treatment.

Tri-element nanozyme PtCuSe as an ingenious cascade catalytic machine for the amelioration of Parkinson's disease-like symptoms.

Parkinson's disease (PD), as the second most common neurodegenerative disease after Alzheimer's, has become intractable with the increasing aging global population. The exploration of nanomedicine has broadened the opportunities for developing novel neuroprotective therapies. In particular, polymetallic functional nanomaterials have been widely used in the biomedicine field in recent years, exhibiting flexible and diversified functions and controllable properties. In this study, a tri-element nanozyme (PtCuSe nanozyme) has been developed with desirable CAT- and SOD-like activities for the cascade scavenging of reactive oxygen species (ROS). In particular, the nanozyme is suitable for relieving nerve cell damage by removing reactive oxygen species in cells and mitigating the behavioral and pathological symptoms in animal models of Parkinson's disease. Therefore, this ingenious tri-element nanozyme may have potential in the treatment of Parkinson's disease and other neurodegenerative diseases.

High-Quality Development of Science and Technology Finance and Logistics Industry in the Yangtze River Economic Belt: Coupling Analysis Based on Deep Learning Model.

Using the entropy method, the coupling coordination model, and the Tobit model, the coupling coordination degree of the high-quality development of science and technology finance and the logistics industry in the Yangtze River Economic Belt in China from 2009 to 2020 is measured, and its influencing factors are found. The study found that the overall coupling coordination degree of the Yangtze River Economic Belt has shown a rapid upward trend; the development gap of the interprovincial coupling coordination degree has a narrowing trend. Except for Sichuan Province, the average coupling coordination degree decreases from the downstream to the upstream; the mechanism analysis shows that the coupling effect of the two. There are scale effect, innovation effect, talent effect, and structure effect; the analysis of influencing factors shows that innovation effect and talent effect have the most obvious promoting effect on the coupled and coordinated development of the two. In addition, the upgrading of the industrial structure, the effective driving of science and technology, the improvement of the logistics foundation, and the further development of finance also have a positive effect on it. Finally, according to the conclusions, suggestions are put forward from five aspects: insisting on innovation, talent training, risk prevention, policy orientation, and industrial structure upgrading, so as to realize the further coupling of high-quality development of technology finance and logistics industry.

Hypertension Was Associated with Higher Tumor Stages in Papillary Thyroid Cancer: A Large Sample Single-Center Study.

Background: Hypertension (HTN) is known to increase the risk of thyroid cancer. However, few studies have explored the association between HTN and the prognostic factors of papillary thyroid cancer (PTC). Methods: We retrospectively evaluated 2838 PTC patients treated with surgery at our center between January 2017 and September 2020. The association between both HTN and antihypertensive drug use and the clinicopathological features of the PTC patients was analyzed. The odds ratios (ORs) were estimated using both univariate and multivariate logistic regression models, which were adjusted for the patients' age, sex, and thyroid-stimulating hormone level. Results: A total of 2838 patients were enrolled in this study, including 409 patients with HTN. In the multivariate analysis, HTN was associated with larger tumor size [OR = 1.51, 95% confidence interval (CI): 1.10-2.07], lymph node metastasis (OR = 1.43, 95% CI: 1.02-1.99), and higher tumor stages (OR = 1.79, 95% CI: 1.12-2.86). There was no statistical difference between females >40 years of age and any pathological features, while a positive association was observed between older males and larger tumors (OR = 1.87, 95% CI: 1.01-3.45), and lymph node metastasis (OR = 2.01, 95% CI: 1.08-3.73). No statistical difference was found in the effects of taking alone calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers, and their combination on the pathological features of PTC. Conclusion: PTC patients with HTN, particularly males of age >40, tend to have invasive features. Common antihypertension therapy appears to exert no effect on the pathological characteristics of these patients.

Application of Metal-Based Nanozymes in Inflammatory Disease: A Review.

Reactive oxygen species (ROS) are metabolites of normal cells in organisms, and normal levels of ROS in cells are essential for maintaining cell signaling and other intracellular functions. However, excessive inflammation and ischemia-reperfusion can cause an imbalance of tissue redox balance, and oxidative stress occurs in a tissue, resulting in a large amount of ROS, causing direct tissue damage. The production of many diseases is associated with excess ROS, such as stroke, sepsis, Alzheimer's disease, and Parkinson's disease. With the rapid development of nanomedicine, nanomaterials have been widely used to effectively treat various inflammatory diseases due to their superior physical and chemical properties. In this review, we summarize the application of some representative metal-based nanozymes in inflammatory diseases. In addition, we discuss the application of various novel nanomaterials for different therapies and the prospects of using nanoparticles (NPs) as biomedical materials.

Injectable agarose hydrogels and doxorubicin-encapsulated iron-gallic acid nanoparticles for chemodynamic-photothermal synergistic therapy against osteosarcoma.

Osteosarcoma is a malignant bone cancer that usually occurs in children and adolescents. Although chemotherapy, radiotherapy and other methods have been used to treat osteosarcoma, these therapeutic regimens fail to cure this disease completely. Herein, doxorubicin-encapsulated iron-gallic acid (FeGA-DOX) nanoparticles (NPs) were fused with agarose hydrogels (AG) for synergistic therapy of osteosarcoma. Under near-infrared laser irradiation, the local temperature of FeGA-DOX NPs was increased. Therefore, tumour cells were killed using photothermal therapy, and AG dissolved to release FeGA-DOX into the cells. Doxorubicin generates hydrogen peroxide, which is then converted to reactive oxygen species (ROS) via FeGA-DOX by the Fenton reaction, inducing tumour cell apoptosis. ROS induced by chemodynamic therapy compensates for the incomplete cure of osteosarcoma cells. The AG-encapsulated NPs could mediate synergistic chemodynamic and photothermal therapy with self-sufficient H2O2, providing a novel therapeutic strategy for osteosarcoma.