Dual elastography to discriminate adjacent stages of fibrosis and inflammation in chronic hepatitis B: A prospective multicenter study.

BACKGROUND AND AIMS: To evaluate the diagnostic performance of dual elastography (dual-elasto) in continuous differentiation of liver fibrosis and inflammation in a large prospective cohort of patients with chronic HBV. APPROACH AND RESULTS: Adults with positive HBsAg for at least 6 months were recruited from 12 medical centers. Participants underwent dual-elasto evaluations. Biopsy was performed 3 days after dual-elasto examination. Four logistic regression models were trained and strung together into series models. Decision trees based on the series models were performed to achieve continuous differentiation of liver fibrosis and inflammation. The influence of inflammation on the fibrosis stage was also evaluated. A total of 560 patients were included in the training set and 240 in the validation set. Areas under the receiver operating characteristic curve of the series model were 0.82, 0.86, 0.93, and 0.96 to predict ≥F1, ≥F2, ≥F3, and F4 in the validation set, which were significantly higher than those of serum markers and shear wave elastography (all p < 0.05), except for the ≥ F1 levels ( p = 0.09). The AUCs of the series model were 0.93, 0.86, 0.95, and 0.84 to predict inflammation stages ≥G1, ≥G2, ≥G3, and G4, respectively. Decision trees realized 5 continuous classifications of fibrosis and inflammation. Inflammation could enhance the mild fibrosis stage classification while showing limited influences on severe fibrosis or cirrhosis diagnosis. CONCLUSIONS: Dual-elasto demonstrated high performance in the continuous discrimination of fibrosis and inflammation in patients with HBV and could be used to diagnose mild fibrosis without the influence of inflammation.

A Prognostic Model for Survival in Patients with Gastric Signet Ring Cell Carcinoma.

INTRODUCTION: The objective of our study was to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRCC). METHODS: A total of 3,408 GSRCC patients between 1975 and 2017 were screened from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors for the construction of a nomogram. The performance of the model was then assessed by the concordance index (C-index), calibration plot, and area under the receiver operating characteristic curve (AUC). Then, the novel nomogram was further assessed by 64 GSRCC patients from our hospital as the external cohort. RESULTS: We identified age, tumor lymph node metastasis (TNM) staging system, surgery, and chemotherapy as significant independent elements of prognosis. On this basis, a nomogram was constructed, with a C-index of OS in the training and validation cohorts of 0.763 (95% CI: 0.751-0.774) and 0.766 (95% CI: 0.748-0.784) and a C-index of CSS of 0.765 (95% CI: 0.753-0.777) and 0.773 (95% CI: 0.755-0.791), respectively. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.848 and 0.885, respectively, and those for predicting CSS were 0.854 and 0.899, respectively, demonstrating the excellent predictive value of the constructed nomogram compared to the traditional AJCC staging system. Similar results were also observed in both the internal and external validation sets. CONCLUSION: The nomogram provided an accurate tool to predict OS and CSS in patients with GSRCC, which can assist clinicians in making predictions about individual patient survival.

Comprehensive mRNA and microRNA analysis revealed the effect and response strategy of freshwater fish, grass carp (Ctenopharyngodon idella) under geosmin exposure.

Geosmin is an environmental pollutant that causes off-flavor in water and aquatic products. The high occurrence of geosmin contamination in aquatic systems and aquaculture raises public awareness, however, few studies have investigated the response pathways of geosmin stress on freshwater fish. In this research, grass carp were exposed to 50 µg/L geosmin for 96 h, liver tissue was sequenced and validated using real-time qPCR. In total of 528 up-regulated genes and 488 down-regulated genes were observed, includes cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase related genes. KEGG analysis showed that chemical carcinogenesis-DNA adducts, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 pathway was enriched. Common genes from the target genes of microRNAs and differential expression genes are enriched in metabolism of xenobiotics cytochrome P450 pathway. Two miRNAs (dre-miR-146a and miR-212-3p) down regulated their target genes (LOC127510138 and adh5, respectively) which are enriched cytochrome P450 related pathway. The results present that geosmin is genetoxic to grass carp and indicate that cytochrome P450 system and UDP-glucuronosyltransferase play essential roles in biotransformation of geosmin. MicroRNAs regulate the biotransformation of geosmin by targeting specific genes, which contributes to the development of strategies to manage its negative impacts in both natural and artificial environments.

Microstructure characterization of different types of chlamydospores in Arthrobotrys flagrans.

The morphological and structural differences of different types of chlamydospore of Arthrobotrys flagrans, a nematophagous fungus, were studied under light microscope and electron microscope to provide a reference for the biological control of parasitic nematodiasis. In this study, A. flagrans isolate F088 dormant chlamydospore and nondormant chlamydospore were selected as the research objects. The structural differences of these spores were observed by optical microscopy through lactol cotton blue, Trypan blue, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining. FunXite -1, 4',6-diamidino-2-phenylindole, and calcofluor white staining were used to observe the metabolic activity, cell wall, and nucleus differences of the two types of spores under fluorescence microscope. Ultrastructure of the two kinds of spores was observed using scanning electron microscope (SEM) and transmission electron microscope (TEM). Since lacto phenol cotton blue, trypan blue staining cannot distinguish dormant spores from dead spores, MTT assay was performed. Fluorescence microscopy observation showed that the cytoplasmic metabolic activity of nondormant spores was stronger than that of dormant spores. The nucleus of dormant spores was bright blue, and their fluorescence was stronger than that of nondormant spores. The cell wall of nondormant spores produced stronger yellow-green fluorescence than that of dormant spores. Ultrastructural observation showed that there were globular protuberances on the surface of the two types of spores but with no significant difference between them. The inner wall of dormant spore possesses a thick zona pellucida with high electron density which was significantly thicker than that of nondormant spores, and their cytoplasm is also changed. In this study, the microstructure characteristics of dormant and nondormant chlamydospores of A. flagrans fungi were preliminarily clarified, suggesting that the state of cell wall and intracellular materials were changed after spores entered to dormancy.

Determination of cyclic adenosine phosphate and protein content in dormant chlamydospore and nondormant chlamydospore of Arthrobotrys flagrans.

Arthrobotrys flagrans, a nematode-eating fungus, is an effective component of animal parasitic nematode biocontrol agents. In the dried formulation, the majority of spores are in an endogenous dormant state. This study focuses on dormant chlamydospore and nondormant chlamydospore of A. flagrans to investigate the differences in cyclic adenosine monophosphate (cAMP) and protein content between the two types of spores. cAMP and soluble proteins were extracted from the nondormant chlamydospore and dormant chlamydospore of two isolates of A. flagrans. The cAMP Direct Immunoassay Kit and Bradford protein concentration assay kit (Coomassie brilliant blue method) were used to detect the cAMP and protein content in two types of spores. Results showed that the content of cAMP in dormant spores of both isolates was significantly higher than that in nondormant spores (p < 0.05). The protein content of dormant spores in DH055 bacteria was significantly higher than that of nondormant spores (p < 0.05). In addition, the protein content of dormant spores of the SDH035 strain was slightly higher than that of nondormant spores, but the difference was not significant (p > 0.05). The results obtained in this study provide evidence for the biochemical mechanism of chlamydospore dormancy or the germination of the nematophagous fungus A. flagrans.

Local and systemic effects of IDH mutations on primary glioma patients.

Adult gliomas are divided into isocitrate dehydrogenase (IDH) wild-type and IDH mutant subtypes according to the new 2021 World Health Organization classification system. However, the local and systemic effects of IDH mutations on primary glioma patients are not well illustrated. Retrospective analysis, immune-cell infiltration analysis, meta-analysis, and immunohistochemistry assay were applied in the present study. The results from our cohort showed that IDH mutant gliomas own a lower proliferating rate compared to that in wild-type gliomas. Patients with mutant IDH exhibited a higher frequency of seizures in both our cohort and the cohort from the meta-analysis. Mutations in IDH result in lower levels of intra-tumour but higher levels of circulating CD4+ and CD8+ T lymphocytes. Levels of neutrophils in both intra-tumour and circulating blood were lower in IDH mutant gliomas. Moreover, IDH mutant glioma patients receiving radiotherapy in combination with chemotherapy exhibited better overall survival with respect to radiotherapy alone. Mutations in IDH alters the local and circulating immune microenvironment, and increases the sensitivity of tumour cell to chemotherapy.

Transcranial Alternating Current Stimulation in a Patient with Ataxia-Ocular Apraxia 2: a Case Report.

Ataxia-ocular apraxia 2 (AOA2) is a rare neurodegenerative autosomal recessive disorder with no effective treatment. In this study, we present the case of a patient diagnosed with AOA2, who experienced walking instability and uncoordinated movement. The patient underwent transcranial alternating current stimulation (tACS) treatment for 4 weeks with follow-up after 1 month. The effectiveness of the treatment was evaluated using the International Cooperative Ataxia Rating Scale (ICARS), the Scale for the Assessment and Rating of Ataxia (SARA), the 9-Hole Peg Test (9HPT), and functional near-infrared spectroscopy (fNIRS). Following treatment, the patient's ataxia symptoms showed significant improvement and continued to be alleviated during the follow-up period, suggesting a lasting effect of tACS treatment. Our findings from this case study provide compelling evidence for the potential of tACS as a treatment option for AOA2.

Short-Term Efficacy of Cerebello-spinal tDCS and Body Weight-Supported Treadmill Training in the Hypertrophic Olivary Degeneration: a Rare Case Report.

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

Analysis of complement system and its related factors in Alzheimer's disease.

Alzheimer's disease (AD) is a primary cause of dementia. The complement system is closely related to AD pathology and may be a potential target for the prevention and treatment of AD. In our study, we conducted a bioinformatics analysis to analyze the role of the complement system and its related factors in AD using Gene Expression Omnibus (GEO) data. We also conducted a functional analysis. Our study verified that 23 genes were closely related to differentially expressed complement system genes in diseases after intersecting the disease-related complement system module genes and differentially expressed genes. The STRING database was used to predict the interactions between the modular gene proteins of the differential complement system. A total of 21 gene proteins and 44 interaction pairs showed close interactions. We screened key genes and created a diagnostic model. The predictive effect of the model was constructed using GSE5281 and our study indicated that the predictive effect of the model was good. Our study also showed enriched negative regulation of Notch signaling, cytokine secretion involved in the immune response pathway, and cytokine secretion involved in immune response hormone-mediated apoptotic signaling pathway. We hope that our study provides a promising target to prevent and delay the onset, diagnosis, and treatment of AD.

Nano drug delivery systems: a promising approach to scar prevention and treatment.

Scar formation is a common physiological process that occurs after injury, but in some cases, pathological scars can develop, leading to serious physiological and psychological effects. Unfortunately, there are currently no effective means to intervene in scar formation, and the structural features of scars and their unclear mechanisms make prevention and treatment even more challenging. However, the emergence of nanotechnology in drug delivery systems offers a promising avenue for the prevention and treatment of scars. Nanomaterials possess unique properties that make them well suited for addressing issues related to transdermal drug delivery, drug solubility, and controlled release. Herein, we summarize the recent progress made in the use of nanotechnology for the prevention and treatment of scars. We examine the mechanisms involved and the advantages offered by various types of nanomaterials. We also highlight the outstanding challenges and questions that need to be addressed to maximize the potential of nanotechnology in scar intervention. Overall, with further development, nanotechnology could significantly improve the prevention and treatment of pathological scars, providing a brighter outlook for those affected by this condition.

Pituitary adenoma with oculomotor cistern extension: membranous anatomy and clinical application.

BACKGROUND: The anatomical basis of pituitary adenomas (PAs) with oculomotor cistern (OC) extension as a growth corridor is overlooked in the literature. In this paper, the authors use the technique of epoxy sheet plastination to study the membranous structure of the OC and validate the results by retrospective analysis of patients with OC extension. METHODS: Eighteen specimens were used to study the membranous anatomy surrounding the OC using the epoxy sheet plastination technique. Thirty-four patients with OC extension were retrospectively reviewed. RESULTS: The OC consisted of two thin membranous layers. The inner layer was extended by the arachnoid layer from the posterior fossa, and the lateral layer consisted of the dura mater sinking from the roof of the cavernous sinus. The oculomotor nerve is more likely to displace with a superolateral trajectory due to the weakness of the posterior dura and the relatively large space in the medial and posterior trajectories, which is consistent with the intraoperative observations. Among the anatomical factors that affect the PA by OC extension, we found that the relative position of the internal carotid artery (ICA) and posterior clinoid process may lead to the narrowing of the OC. Of 34 cases, 28 patients achieved total resection. Among 24 preoperative patients with oculomotor nerve palsy, 16 cases were relieved to varying degrees postoperatively. There was no ICA injury or severe intracranial infection found in any of the patients. CONCLUSIONS: Extension into the OC is influenced by two anatomical factors: a weak point in the dura in the posterior OC and a potential space beyond this region of the dura. Meticulous knowledge of the membranous anatomy in endoscopic endonasal surgery is required to safely and effectively resect PA with OC extension.

How can infectious medical waste be forecasted and transported during the COVID-19 pandemic? A hybrid two-stage method.

The COVID-19 pandemic has caused an unforeseen collapse of infectious medical waste (IMW) and an abrupt smite of the conveying chain. Hospitals and related treatment centers face great challenges during the pandemic because mismanagement may lead to more severe life threats and enlarge environmental pollution. Opportune forecasting and transportation route optimization, therefore, are crucial to coping with social stress meritoriously. All related hospitals and medical waste treatment centers (MWTCs) should make decisions in perspective to reduce the economic pressure and infection risk immensely. This study proposes a hybrid dynamic method, as follows: first to forecast confirmed cases via infectious disease modeling and analyze the association between IMW outflows and cases; next to construct a model through time-varying factors and the lagging factor to predict the waste quantity; and then to optimize the transportation network route from hospitals to MWTCs. For demonstration intentions, the established methodology is employed to an illustrative example. Based on the obtained results, in finding the process of decision making, cost becomes the common concern of decision-makers. Actually, the infection risk among publics has to be considered simultaneously. Therefore, realizing early warning and safe waste management has an immensely positive effect on epidemic stabilization and lifetime health.

A review of autophagy mechanism of statins in the potential therapy of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegeneration csharacterized by amyloid-ß (Aß) deposition and abnormally phosphorylated Tau protein aggregation. Autophagy, as an important cellular metabolic activity, is closely related to the production, secretion and clearance of Aß peptide and Tau phosphorylation level. Therefore, autophagy may become a potential target for AD treatment. A large number of molecules are involved in the mammalian target of rapamycin (mTOR)-dependent or mTOR-independent pathway of autophagy. More and more evidences show that statins can intervene autophagy by regulating the activity or expression level of autophagy-related proteins and genes. On the one hand, statins can induce autophagy through Sirtuin1 (SIRT1), P21, nuclear P53 and adenylate activated protein kinase (AMPK). On the other hand, statins inhibit the mevalonate metabolism pathway, thereby interfering with the prenylation of small GTPases, leading to autophagy dysfunction. Statins can also reduce the levels of LAMP2 and dynein, destroying autophagy. In this review, we focused on the role of autophagy in AD and the autophagy mechanism of statins in the potential treatment of AD.

Long distance signal transduction in response to environmental changes in plants.

The vascular system is responsible for the communication of information between different organs and the environment as a whole, so that it can coordinate the development of plants and respond to the changes of the environment. The signal substances moving in the vascular system are called long-distance signals. In recent years, it has been found that some long-distance molecular signals, such as microRNA, mRNA, small peptides, hormones, second messengers and proteins, can transmit extracellular stimuli from sensing tissues to target organs, so as to systematically regulate plant development process and environmental response. In this review, we summarize the molecular mechanisms of long-distance moving RNA, small peptides and proteins in plants to regulate plant organ development, nutrient uptake and stress resistance. The application potential of this field in crop breeding was discussed and prospected, in order to provide a theoretical basis for the application of genetics and breeding in crops.

High linear polarization, narrow linewidth hybrid semiconductor laser with an external birefringence waveguide Bragg grating.

We demonstrate a high linear polarization, narrow linewidth hybrid laser composed of a semiconductor gain chip and a high birefringence waveguide Bragg grating (WBG). The laser operates in the C-band, and a maximum output power of 8.07 mW is obtained in the fiber waveguide. With careful temperature tuning, the hybrid laser can operate in a single longitudinal mode state from above the threshold current to 410 mA. The side mode suppression ratio (SMSR) reaches a value of 50.2 dB, and the polarization extinction ratio exceeds 39.6 dB. We numerically analyze the linewidth suppression for the Bragg grating based on adiabatic chirp theory. The hybrid laser shows a narrow linewidth of 4.15 kHz and a low relative intensity noise (RIN) of <-155 dBc/Hz, providing a high-performance light source for coherent light communication.

Thickness, vessel density of retina and choroid on OCTA in young adults (18-24 years old).

PURPOSE: The purpose of this study was to quantify thickness, vessel density (VD) of retina and choroid in young adults (18-24 years old) using OCTA. METHODS: This observational, cross-sectional study included 154 eyes from 77 young myopic adults. En-face angiogram OCTA was performed on a 3.00 × 3.00 mm region centered on the macula. Automated thickness calculations and macular maps were measured. Spherical equivalent refraction (SER) and AL were examined to determine associations with thickness, vessel density (VD) of retina and choroid. RESULTS: A total of 148 healthy eyes from 77 young myopic adults (29 males and 48 females) with a mean age of 21.80 ± 1.32 years (range: 18-24 years) were included. The mean SER and AL were - 4.06 ± 2.26D and 25.25 ± 1.28 mm, respectively. The mean retinal thickness (RT, ILM-RPE layer) was 240.91 ± 13.36 µm, the retinal superficial (SVD) and deep vessel density (DVD) in fovea region were 18.35 ± 4.77% and 32.99 ± 6.01%, respectively. The foveal avascular zone (FAZ) area was 0.31 ± 0.10 mm2. The mean subfoveal choroidal thickness (SFCT) and choriocapillaris (CC) perfusion area were 232.16 ± 56.65 µm and 2.17 ± 0.10 mm2, respectively. By Pearson's correlation analysis, SER was revealed to be negatively correlated with RT (r = -0.180, p = 0.028) and DVD (r = -0.185, p = 0.025) in fovea region. SER was revealed to be positively correlated with RT in nasal (r = 0.224, p = 0.006) and inferior (r = 0.217, p = 0.008) regions. AL was revealed to be positively correlated with RT (r = 0.250, p = 0.002) and DVD (r = 0.284, p < 0.001) in fovea region. SER was revealed to be positively correlated with SFCT (r = 0.486, p < 0.001). AL was revealed to be negatively correlated with FAZ area (r = -0.232, p = 0.005) and SFCT (r = -0.407). RT was revealed to be negatively correlated with FAZ area (r = -0.645, p < 0.001). SER (r = -0.079), AL (r = 0.071) and SFCT (r = 0.089) did not correlate significantly with the CC perfusion area (all p > 0.05). CONCLUSION: Myopic eyes present increased RT, DVD and thinned SFCT in fovea, while no significant correlation could be found between SER, AL, SFCT and CC perfusion area. It may indicate that the SFCT thinning may be secondary to ocular elongation, while the CC perfusion area may be a factor independent of AL growth.

Impacts of CR1 genetic variants on cerebrospinal fluid and neuroimaging biomarkers in alzheimer's disease.

BACKGROUND: The complement component (3b/4b) receptor 1 gene (CR1) gene has been proved to affect the susceptibility of Alzheimer's disease (AD) in different ethnic and districts groups. However, the effect of CR1 genetic variants on amyloid ß (Aß) metabolism of AD human is still unclear. Hence, the aim of this study was to investigate genetic influences of CR1 gene on Aß metabolism. METHODS: All data of AD patients and normal controls (NC) were obtained from alzheimer's disease neuroimaging initiative database (ADNI) database. In order to assess the effect of each single nucleotide polymorphism (SNP) of CR1 on Aß metabolism, the PLINK software was used to conduct the quality control procedures to enroll appropriate SNPs. Moreover, the correlation between CR1 genotypes and Aß metabolism in all participants were estimated with multiple linear regression models. RESULTS: After quality control procedures, a total of 329 samples and 83 SNPs were enrolled in our study. Moreover, our results identified five SNPs (rs10494884, rs11118322, rs1323721, rs17259045 and rs41308433), which were linked to Aß accumulation in brain. In further analyses, rs17259045 was found to decrease Aß accumulation among AD patients. Additionally, our study revealed the genetic variants in rs12567945 could increase CSF Aß42 in NC population. CONCLUSIONS: Our study had revealed several novel SNPs in CR1 genes which might be involved in the progression of AD via regulating Aß accumulation. These findings will provide a new basis for the diagnosis and treatment AD.

Synovial and pulmonary dysfunctions are induced by crosstalk of Smad and Erk pathways in an arthritis model.

In the current experiment, the effects of transforming growth factor (TGF)-ß1/Smad and ERK pathway crosstalk on synovial and pulmonary systems during rheumatoid arthritis have been investigated. For this purpose, rats were divided into normal control (NC) and model control (MC) groups. In the MC group, 0.1 ml Freund's complete adjuvant was injected intradermally into the right hind paw, and the resulting inflammation represented a rheumatoid arthritis model. Joint swelling and changes in lung functions were observed in arthritic rats. Synovial and lung were observed by light and electron microscopies. Enzyme-linked immunosorbent assays were used to detect TGF-ß1, interleukin (IL)-1ß, IL-4, IL-10, interferon-γ (IFN-γ), connective tissue growth factor (CTGF), and fibroblast growth factor (FGF). PCR, immunohistochemistry, and immunoblotting were used to detect changes in Smad and ERK pathways of synovial and lung tissues. Compared with the NC group, toe swelling was elevated in the MC group. Pulmonary functions FEV1, FEF50, FEF75, MMF, and PEF were decreased (P< 0.01). Serum cytokines IL-1ß, IL-4, TGF-ß1, and CTGF were increased, while IFN-γ, IL-10, Th1/Th2 cell ratio, and FGF were decreased (P< 0.01 or P< 0.05). Expression of TGF-ß1 and Smad2/3/4 mRNAs and TGF-ß1, TßRI, TßRII, Smad2/3, p-Smad2/3, and Smad4 proteins in the synovial membrane and lung tissue were increased, and expression of Smad7 mRNA and protein was decreased (P<0.01) or P<0.05). Expression of ERK2 mRNA and p-ERK1/2 protein was increased in the synovial membrane and lung tissue, and expression of ERK1/2 mRNAs and ERK1/2 and p-ERK1/2 proteins was increased in lung tissue (P< 0.01 or P< 0.05). Correlation analysis showed that FEV1 was negatively correlated with TGF-ß1 mRNA and protein in arthritic rats, FEF25 was negatively correlated with Smad4 protein, and FEF50 was negatively correlated with the TßRII protein, and FEF75, TGF-ß1 and Smad3 mRNAs. There was a negative correlation between Smad2/3 protein and a negative correlation between PEF and TGF-ß1 protein (P< 0.05). FEF50 and MMF were positively correlated with Smad7 mRNA (P< 0.05). FEV1 was negatively correlated with ERK2 mRNA, and FEF25 was negatively correlated with p-ERK1/2 protein. FEF75 and MMF were negatively correlated with ERK1/2 and p-ERK1/2, respectively (P< 0.05). ERK1 mRNA was positively correlated with Smad3 mRNA and TßRII protein, ERK2 mRNA was positively correlated with p-Smad2/3, and ERK1/2 protein was positively correlated with Smad2 mRNA, Smad4 protein, p-ERK1/2 protein, Smad4 mRNA, and p-Smad2/3 protein (P< 0.05). p-ERK1/2 protein was negatively correlated with Smad7 protein (P< 0.05). It is concluded that arthritic rats have synovial and systemic pulmonary damage. Smad and ERK pathway crosstalk leads to systemic lesions. Smad and ERK pathways are gradually activated by phosphorylation under the induction of the TGF-ß1 promoter, and then participate in transcriptional activities, leading to the increase in synovial inflammation of arthritis, pulmonary lesions, and decreases in lung functions.

A Theoretical Study of the Recently Suggested MnVII Mechanism for O-O Bond Formation in Photosystem II.

The mechanism for water oxidation in photosystem II has been a major topic for several decades. The active catalyst has four manganese atoms connected by bridging oxo bonds, in a complex termed the oxygen-evolving complex (OEC), which also includes a calcium atom. The O-O bond of oxygen is formed after absorption of four photons in a state of the OEC termed S4. There has been essential consensus that in the S4 state, all manganese atoms are in the Mn(IV) oxidation state. However, recently there has been a suggestion that one of the atoms is in the Mn(VII) state. In the present computational study, the feasibility of that proposal has been investigated. It is here shown that the mechanism involving Mn(VII) has a much higher barrier for forming O2 than the previous proposal with four Mn(IV) atoms.

Newly excysted juveniles of Fasciola gigantica trigger the release of water buffalo neutrophil extracellular traps in vitro.

Polymorphonuclear neutrophils (PMNs) are the most abundant leukocytes and are among the first line of immune system defense. PMNs can form neutrophil extracellular traps (NETs) in response to some pathogens. The release of NETs plays an important role in trapping and killing invading parasites. However, the effects of NETs on parasitic trematode infections remain unclear. In the present study, water buffalo NET formation, triggered by the newly excysted juveniles (NEJs) of Fasciola gigantica, was visualized by scanning electron microscopy. The major components of the structure of NETs were characterized by immunofluorescence. Viability of flukes incubated with water buffalo PMNs were examined under light microscopy. The results revealed that F. gigantic juveniles triggered PMN-mediated NETs. These NETs were confirmed to comprise the classic characteristics of NETs: DNA, histones, myeloperoxidase and neutrophil elastase. Although NETs were formed in response to viable larvae, the larvae were not killed in vitro. These results suggest that NET formation may serve as a mechanism to hamper the migration of large larvae to facilitate immune cells to kill them. This study demonstrates, for the first time, that parasitic trematode juveniles can trigger NET formation.