Radiomics analysis of T1WI and T2WI magnetic resonance images to differentiate between IgG4-related ophthalmic disease and orbital MALT lymphoma.

BACKGROUND: Preoperative differentiation between IgG4-related orbital disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma has a significant impact on clinical decision-making. Our research aims to construct and evaluate a magnetic resonance imaging (MRI)-based radiomics model to assist clinicians to better identify IgG4-ROD and orbital MALT lymphoma and make better preoperative medical decisions. METHODS: MR images and clinical data from 20 IgG4-ROD patients and 30 orbital MALT lymphoma patients were classified into a training (21 MALT; 14 IgG4-ROD) or validation set (nine MALT; six IgG4-ROD). Radiomics features were collected from T1-weighted (T1WI) and T2-weighted images (T2WI). Student's t-test, the least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA) were conducted to screen and select the radiomics features. Support vector machine (SVM) classifiers developed from the selected radiomic features for T1WI, T2WI and combined T1WI and T2WI were trained and tested on the training and validation set via five-fold cross-validation, respectively. Diagnostic performance of the classifiers were evaluated with area under the curve (AUC) readings of the receiver operating characteristic (ROC) curve, and readouts for precision, accuracy, recall and F1 score. RESULTS: Among 12 statistically significant features from T1WI, four were selected for SVM modelling after LASSO analysis. For T2WI, eight of 51 statistically significant features were analyzed by LASSO followed by PCA, with five features finally used for SVM. Combined analysis of T1WI and T2WI features selected two and four, respectively, for SVM. The AUC values for T1WI and T2WI classifiers separately were 0.722 ± 0.037 and 0.744 ± 0.027, respectively, while combined analysis of T1WI and T2WI classifiers further enhanced the classification performances with AUC values ranging from 0.727 to 0.821. CONCLUSION: The radiomics model based on features from both T1WI and T2WI images is effective and promising for the differential diagnosis of IgG4-ROD and MALT lymphoma. More detailed radiomics features and advanced techniques should be considered to further explore the differences between these diseases.

Irisin alleviates LPS-induced liver injury and inflammation through inhibition of NLRP3 inflammasome and NF-κB signaling.

Lipopolysaccharide (LPS) provokes severe inflammation and cell death in sepsis, with liver being the major affected organ. Up-to-date, neither the mechanism of action nor target treatment is readily available for LPS-induced liver injury. This study examined the effect of irisin, an endogenous hormonal peptide, on LPS-induced liver injury using animal and cell models, and the mechanism involved with a special focus on pyroptosis. Irisin is known to regulate glucose metabolism, inflammation, and immune response, while our earlier work denoted the anti-inflammatory and anti-apoptotic properties for irisin. Inflammatory factors and AST/ALT were also detected. Pyroptosis, apoptosis, and reactive oxygen species (ROS) were evaluated using PI staining, TUNEL staining, DCFH-DA fluorescence, and western blot, respectively. Our results indicated that irisin attenuated LPS-induced liver injury and release of inflammatory cytokines. Increased activity of NLRP3 inflammasome was discovered in LPS-challenged Raw264.7 cells, along with elevated levels of inflammation and apoptosis, the effects of which were mediated by activation of ROS and nuclear factor κB (NF-κB) signaling. These changes were reversed following irisin treatment. Our study demonstrated that irisin countered LPS-mediated liver injury via inhibiting apoptosis, NLRP3 inflammasome activation and NF-κB signaling. These findings revealed the role of irisin as a promising new anti-pyroptosis/apoptosis agent to reconcile the onset and progression of septic liver injury.

Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China.

BACKGROUND: Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial. Our study was to investigate risk factors of post-bronchiolitis recurrent wheezing. METHODS: Infants with bronchiolitis were enrolled from November 2016 through March 2017. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed up every 3 months for a duration of 2 years by telephone or at outpatient appointments. RESULTS: We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with history of eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P < 0.05); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P > 0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR] = 5.622; 95% confidence interval [CI], 1.3-24.9; P = 0.023). CONCLUSION: The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.

Deletion of TLR4 attenuates lipopolysaccharide-induced acute liver injury by inhibiting inflammation and apoptosis.

Septic acute liver injury is one of the leading causes of fatalities in patients with sepsis. Toll-like receptor 4 (TLR4) plays a vital role in response to lipopolysaccharide (LPS) challenge, but the mechanisms underlying TLR4 function in septic injury remains unclear. In this study, we investigated the role of TLR4 in LPS-induced acute liver injury (ALI) in mice with a focus on inflammation and apoptosis. Wild-type (WT) and TLR4-knockout (TLR4-/-) mice were challenged with LPS (4 mg/kg) for 6 h. TLR4 signaling cascade markers (TLR4, MyD88, and NF-κB), inflammatory markers (TNFα, IL-1ß, and IL-6), and apoptotic markers (Bax, Bcl-2, and caspase 3) were evaluated. We showed that LPS challenge markedly increased the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and other liver pathological changes in WT mice. In addition, LPS challenge elevated the levels of liver carbonyl proteins and serum inflammatory cytokines, upregulated the expression of TLR4, MyD88, and phosphorylated NF-κB in liver tissues. Moreover, LPS challenge significantly increased hepatocyte apoptosis, caspase 3 activity, and Bax level while suppressing Bcl-2 expression in liver tissues. These pathological changes were greatly attenuated in TLR4-/- mice. Similar pathological responses were provoked in primary hepatic Kupffer cells isolated from WT and TLR4-/- mice following LPS (1 µg/mL, 6 h) challenge. In summary, these results demonstrate that silencing of TLR4 attenuates LPS-induced liver injury through inhibition of inflammation and apoptosis via TLR4/MyD88/NF-κB signaling pathway. TLR4 deletion confers hepatoprotection against ALI induced by LPS, possibly by repressing macrophage inflammation and apoptosis.

Association of cardiotrophin-like cytokine factor 1 levels in peripheral blood mononuclear cells with bone mineral density and osteoporosis in postmenopausal women.

BACKGROUND: Recent research has suggested that cardiotrophin-like cytokine factor 1 (CLCF1) may be an important regulator of bone homeostasis. Furthermore, a whole gene chip analysis suggested that the expression levels of CLCF1 in the peripheral blood mononuclear cells (PBMCs) were downregulated in postmenopausal women with osteoporosis. This study aimed to assess whether the expression levels of CLCF1 in PBMCs can reflect the severity of bone mass loss and the related fracture risk. METHODS: In all, 360 postmenopausal women, aged 50 to 80 years, were included in the study. A survey to evaluate the participants' health status, measurement of bone mineral density (BMD), routine blood test, and CLCF1 expression level test were performed. RESULTS: Based on the participants' bone health, 27 (7.5%), 165 (45.83%), and 168 (46.67%) participants were divided into the normal, osteopenia, and osteoporosis groups, respectively. CLCF1 protein levels in the normal and osteopenia groups were higher than those in the osteoporosis group. While the CLCF1 mRNA level was positively associated with the BMD of total femur (r = 0.169, p = 0.011) and lumbar spine (r = 0.176, p = 0.001), the protein level was positively associated with the BMD of the lumbar spine (r = 0.261, p < 0.001), femoral neck (r = 0.236, p = 0.001), greater trochanter (r = 0.228, p = 0.001), and Ward's triangle (r = 0.149, p = 0.036). Both the mRNA and protein levels were negatively associated with osteoporosis development (r = - 0.085, p = 0.011 and r = - 0.173, p = 0.014, respectively). The association between CLCF1 protein level and fracture risk was not significant after adjusting for BMD. CONCLUSIONS: To our knowledge, this is the first clinical study to show that CLCF1 expression levels in the PBMCs of postmenopausal women can reflect the amount of bone mass or the severity of bone mass loss.

Pathogen analysis of pertussis-like syndrome in children.

BACKGROUND: The aim of the study was to identify the pathogens, in addition to bordetella pertussis (B. pertussis), which cause pertussis-like syndrome in children and to compare clinical presentation between those with B. pertussis and pertussis-like syndrome. METHODS: A cross-sectional analysis was conducted from March 2016 to September 2018. In total, 281 children with suspected pertussis infections were enrolled in this study. Multi-pathogen detection was performed. RESULTS: In total, 281 children were enrolled including 139 males and 142 females. Among them, 149 (53.0%) were B. pertussis positive, and 72 (15.6%) children tested positive for other pathogens. Mycoplasma pneumoniae (MP, 27 cases) was the most common causative pathogen in pertussis-like syndrome, followed by human rhinovirus (HRV, 23 cases), Streptococcus pneumoniae (SP, 13 cases), Haemophilus influenzae (HI, 12 cases) and parainfluenza virus 3 (Pinf-3, 9 cases). Children in the B. pertussis group had a higher rate of vaccination and longer hospital stay (P < 0.05). B. pertussis was more likely to be detected in winter than other pathogens, but this difference was not significant (P = 0.074). The number of white blood cells, neutrophils and blood platelets was significantly higher in children in the B. pertussis than in the pertussis-like group (P < 0.05). In addition, the percentage of CD3-CD19+ cells was significantly higher in the B. pertussis group (P = 0.018). CONCLUSION: About half of the children with pertussis-like syndrome were B. pertussis positive. MP was the second most common causative pathogen followed by HRV, SP, HI and Pinf-3. Children infected with B. pertussis had longer hospital stay and higher numbers of white blood cells, neutrophil and blood platelets compared with other pathogens.

Parkin deficiency accentuates chronic alcohol intake-induced tissue injury and autophagy defects in brain, liver and skeletal muscle.

Alcoholism leads to organ injury including mitochondrial defect and apoptosis with evidence favoring a role for autophagy dysregulation in alcoholic damage. Parkin represents an autosomal recessive inherited gene for Parkinson's disease and an important member of selective autophagy for mitochondria. The association between Parkinson's disease and alcoholic injury remains elusive. This study aimed to examine the effect of parkin deficiency on chronic alcohol intake-induced organ injury in brain, liver and skeletal muscle (rectus femoris muscle). Adult parkin-knockout (PRK-/-) and wild-type mice were placed on Liber-De Carli alcohol liquid diet (4%) for 12 weeks prior to assessment of liver enzymes, intraperitoneal glucose tolerance, protein carbonyl content, apoptosis, hematoxylin and eosin morphological staining, and mitochondrial respiration (cytochrome c oxidase, NADH:cytochrome c reductase and succinate:cytochrome c reductase). Autophagy protein markers were monitored by western blot analysis. Our data revealed that chronic alcohol intake imposed liver injury as evidenced by elevated aspartate aminotransferase and alanine transaminase, glucose intolerance, elevated protein carbonyl formation, apoptosis, focal inflammation, necrosis, microvesiculation, autophagy/mitophagy failure and dampened mitochondrial respiration (complex IV, complexes I and III, and complexes II and III) in the brain, liver and rectus femoris skeletal muscle. Although parkin ablation itself did not generate any notable effects on liver enzymes, insulin sensitivity, tissue carbonyl damage, apoptosis, tissue morphology, autophagy or mitochondrial respiration, it accentuated alcohol intake-induced tissue damage, apoptosis, morphological change, autophagy/mitophagy failure and mitochondrial injury without affecting insulin sensitivity. These data suggest that parkin plays an integral role in the preservation against alcohol-induced organ injury, apoptosis and mitochondrial damage.

Cross-Linked Pectin Nanofibers with Enhanced Cell Adhesion.

Polysaccharides display poor cell adhesion due to the lack of cell binding domains. This severely limits their applications in regenerative medicine. This study reports novel cross-linked pectin nanofibers with dramatically enhanced cell adhesion. The nanofibers are prepared by at first oxidizing pectin with periodate to generate aldehyde groups and then cross-linking the nanofibers with adipic acid dihydrazide to covalently connect pectin macromolecular chains with adipic acid dihydrazone linkers. The linkers may act as cell binding domains. Compared with traditional Ca2+-cross-linked pectin nanofibers, the pectin nanofibers with high oxidation/cross-linking degree exhibit much enhanced cell adhesion capability. Moreover, the cross-linked pectin nanofibers exhibit excellent mechanical strength (with Young's modulus ∼10 MPa) and much enhanced body degradability (degrade completely in 3 weeks or longer time). The combination of excellent cell adhesion capability, mechanical strength, and body degradability suggests that the cross-linked pectin nanofibers are promising candidates for in vivo applications such as tissue engineering and wound healing. This cross-linking strategy may also be used to improve the cell adhesion capability of other polysaccharide materials.

Identification and characterization of proliferative retinopathy-related long noncoding RNAs.

Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery, which can lead to severe vision reduction. Long non-coding RNAs (lncRNAs) play critical roles in many biological processes and disease development. We attempted to determine the role of lncRNAs in the setting of PVR. Microarray analysis revealed that 78 lncRNAs were abnormally expressed in the epiretinal membranes (ERMs) of PVR patients, including 48 up-regulated and 30 down-regulated lncRNA transcripts. We subsequently focus on one lncRNA, MALAT1, and investigated its expression pattern in the biofluid of PVR patients. MALAT1 was significantly up-regulated in the cellular and plasma fraction of peripheral blood in PVR patients. MALAT1 expression was obviously reduced after PVR operation. In vitro experiments revealed the role of MALAT1 in regulating RPE proliferation and migration, which is critical for ERMs formation. This study suggests that lncRNAs are the potential regulators of PVR pathology. MALAT1 is a potential prognostic indicator and a target for the diagnosis and gene therapy for PVR diseases.

Qualitative and Quantitative Analysis of Major Triterpenoids in Alismatis Rhizoma by High Performance Liquid Chromatography/Diode-Array Detector/Quadrupole-Time-of-Flight Mass Spectrometry and Ultra-Performance Liquid Chromatography/Triple Quadrupole Mass Spectrometry.

Alismatis Rhizoma (AMR) is a well-known natural medicine with a long history in Chinese medicine and has been commonly used for treating a wide range of ailments related to dysuria, edema, nephropathy, hyperlipidaemia, diabetes, inflammation as well as tumors in clinical applications. Most beneficial effects of AMR are attributed to the presence of protostane terpenoids, the major active ingredients of Alismatis Rhizoma (AMR). In this study, a systematic high performance liquid chromatography/diode-array detector/quadrupole-time-of-flight mass spectrometry (HPLC-DAD-Q-TOF MS) and ultra-performance liquid chromatography/triple quadrupole mass spectrometry (UPLC-QqQ MS) method was developed for qualitative and quantitative analyses of the major AMR triterpenoids. First, a total of 25 triterpenoid components, including 24 known compounds and one new compound were identified by comparison with UV spectra, molecular ions and fragmentation behaviors of reference standards or the literature. Second, an efficient method was established for the rapid simultaneous determination of 14 representative triterpenoids by UPLC-QqQ MS. Forty-three batches of AMR were analyzed with linearity (r, 0.9980-0.9999), intra-day precision (RSD, 1.18%-3.79%), inter-day precision (RSD, 1.53%-3.96%), stability (RSD, 1.32%-3.97%), repeatability (RSD, 2.21%-4.25%), and recovery (98.11%-103.8%). These results indicated that new approaches combining HPLC-DAD-Q-TOF MS and UPLC-QqQ MS are applicable in the qualitative and quantitative analysis of AMR.

Research status and prospects of pituitary adenomas in conjunction with neurological and psychiatric disorders and the tumor microenvironment.

Patients with pituitary neuroendocrine tumors (PitNETs) often experience neuropsychiatric disorders due to factors such as hormonal imbalances, and inadequate management of medications, surgeries, and radiation therapies. Commonly observed disorders include depression, anxiety, and cognitive dysfunction, which significantly impact patients' quality of life and prognosis. PitNETs have a significant presence of immune cells within the tumor microenvironment (TME), predominantly macrophages and T lymphocytes. These immune cells secrete a variety of cytokines, growth factors, and chemokines, which regulate the biological behaviors of PitNETs, including tumor initiation, proliferation, migration, invasion, and angiogenesis. In addition, this review provides a pioneering summary of the close relationships between the aberrant secretion of proinflammatory cytokines within the TME of PitNETs and the occurrence of neuropsychiatric disorders, along with their potential underlying mechanisms. The cytokines produced as a result of TME dysregulation may affect various aspects of the central nervous system, including neurotransmitter metabolism, neuroendocrine function, and neurovascular plasticity, thereby leading to a higher susceptibility to neurobehavioral disorders in PitNET patients.

Elucidation of the dominant factors influencing N2O emission in water-level fluctuation zones in a karst canyon reservoir, southwest China.

The water-level fluctuations zones (WLFZs) are crucial transitional interfaces within river-reservoir systems, serving as hotspots for N2O emission. However, the comprehension of response patterns and mechanisms governing N2O emission under hydrological fluctuation remains limited, especially in karstic canyon reservoirs, which introduces significant uncertainty to N2O flux assessments. Soil samples were collected from the WLFZs of the Hongjiadu (HJD) Reservoir along the water flow direction from transition zone (T1 and T2) to lacustrine zone (T3, T4 and T5) at three elevations for each site. These soil columns were used to conduct simulation experiments under various water-filled pore space gradients (WFPSs) to investigate the potential N2O flux pattern and elucidate the underlying mechanism. Our results showed that nutrient distribution and N2O flux pattern differed significantly between two zones, with the highest N2O fluxes in the transition zone sites and lacustrine zone sites were found at 75 % and 95 % WFPS, respectively. Soil nutrient loss in lower elevation areas is influenced by prolonged impoundment durations. The higher N2O fluxes in the lacustrine zone can be attributed to increased nutrient levels resulting from anthropogenic activities. Furthermore, correlation analysis revealed that soil bulk density significantly impacted N2O fluxes across all sites, while NO3-and SOC facilitated N2O emissions in T1-T2 and T4-T5, respectively. It was evident that N2O production primarily contributed to nitrification in the transition zone and was constrained by the mineralization process, whereas denitrification dominated in the lacustrine zone. Notably, the annual N2O efflux from WLFZs accounted for 27 % of that from the water-air interface in HJD Reservoir, indicating a considerably lower contribution than anticipated. Nevertheless, this study highlights the significance of WLFZs as a vital potential source of N2O emission, particularly under the influence of anthropogenic activities and high WFPS gradient.

MAGNESIUM SULFATE AMELIORATES HISTONE-INDUCED COAGULATION DYSFUNCTION AND LUNG DAMAGE IN MICE.

ABSTRACT: Introduction: Extracellular histones have been determined as significant mediators of sepsis, which can induce endothelial cell injury and promote coagulation activation, and ultimately contribute to multiorgan failure. Evidence suggests that magnesium sulfate (MgSO 4 ) exerts a potential coagulation-modulating activity; however, whether MgSO 4 ameliorates histone-induced coagulation dysfunction and organ damage remains unclear. Methods: To measure circulating histone levels, blood specimens were collected from septic patients and mice, and the relationship between circulating histone levels, coagulation parameters, and Mg 2+ levels in sepsis was investigated. Furthermore, to explore the possible protective effects of MgSO 4 , we established a histone-induced coagulation model in mice by intravenous histone injection. The survival rate of mice was assessed, and the histopathological damage of the lungs (including endothelial cell injury and coagulation status) was evaluated using various methods, including hematoxylin and eosin staining, immunohistochemistry, immunofluorescence, electron microscopy, and quantitative polymerase chain reaction. Results: The circulating histone levels in septic patients and mice were significantly associated with several coagulation parameters. In septic patients, histone levels correlated negatively with platelet counts and positively with prothrombin time and D-dimer levels. Similarly, in cecal ligation and puncture mice, histones correlated negatively with platelet counts and positively with D-dimer levels. Interestingly, we also observed a positive link between histones and Mg 2+ levels, suggesting that Mg 2+ with anticoagulant activity is involved in histone-mediated coagulation alterations in sepsis. Further animal experiments confirmed that MgSO 4 administration significantly improved survival and attenuated histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage in mice. Conclusion: These results suggest that therapeutic targeting of histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage, for example, with MgSO 4 , may be protective in septic individuals with elevated circulating histone levels.

Chronic increasing nitrogen and endogenous phosphorus release from sediment threaten to the water quality in a semi-humid region reservoir.

The water quality in the drinking water reservoir directly affects people's quality of life and health. When external pollution input is effectively controlled, endogenous release is considered the main cause of water quality deterioration. As the major nitrogen (N) and phosphorus (P) sources in reservoirs, sediment plays a vital role in affecting the water quality. To understand the spatial and temporal variation of N and P in the sediment, this study analyzed the current characteristics and cumulative effects of a semi-humid reservoir, Yuqiao Reservoir, in North China. The N and P concentrations in the reservoir sediment were decreased along the flow direction, while the minimum values were recorded at the central sediment profile. External input and algal deposition were the main factors leading to higher sediment concentrations in the east (Re-E) and west (Re-W) areas of reservoir sediment profiles. According to the long-term datasets, the peaks of both sediment total nitrogen content and deposition rate were observed in the 2010s, which has increased about three times and six times than in the1990s, respectively. Therefore, the increase in phosphorus concentration may be the main reason for eutrophication in water in recent years. The mineralization of organic matter has a significant promoting effect on releasing N and P from sediments, which will intensify eutrophication in water dominated by P and bring huge challenges to water environment management. This study highlights that the current imbalance in N and P inputs into reservoirs and the endogenous P release from sediment will have a significant impact on water quality.

Magnesium alleviates extracellular histone-induced apoptosis and defective bacterial phagocytosis in macrophages by regulating intracellular calcium signal.

Extracellular histones have been determined as important mediators of sepsis, which induce excessive inflammatory responses in macrophages and impair innate immunity. Magnesium (Mg2+), one of the essential nutrients of the human body, contributes to the proper regulation of immune function. However, no reports indicate whether extracellular histones affect survival and bacterial phagocytosis in macrophages and whether Mg2+ is protective against histone-induced macrophage damage. Our clinical data revealed a negative correlation between circulating histone and monocyte levels in septic patients, and in vitro experiments confirmed that histones induced mitochondria-associated apoptosis and defective bacterial phagocytosis in macrophages. Interestingly, our clinical data also indicated an association between lower serum Mg2+ levels and reduced monocyte levels in septic patients. Moreover, in vitro experiments demonstrated that Mg2+ attenuated histone-induced apoptosis and defective bacterial phagocytosis in macrophages through the PLC/IP3R/STIM-mediated calcium signaling pathway. Importantly, further animal experiments proved that Mg2+ significantly improved survival and attenuated histone-mediated lung injury and macrophage damage in histone-stimulated mice. Additionally, in a cecal ligation and puncture (CLP) + histone-induced injury mouse model, Mg2+ inhibited histone-mediated apoptosis and defective phagocytosis in macrophages and further reduced bacterial load. Overall, these results suggest that Mg2+ supplementation may be a promising treatment for extracellular histone-mediated macrophage damage in sepsis.

Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy.

Thyroid associated ophthalmopathy (TAO) is an orbital autoimmune inflammatory disease that is commonly associated with thyroid dysfunction. Although the etiology of TAO is unclear, ROS accumulation and oxidative stress have been closely linked to the pathogenesis of TAO. Ferroptosis is an iron-dependent programmed cell death characterized by intracellular labile iron levels, excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation. Currently, there are few reports regarding the role of ferroptosis in TAO. This article aimed to identify ferroptosis-related genes (FRGs) with diagnostic and therapeutic potential in TAO and explore their relationship with immune cells and lncRNAs. GSE58331 was downloaded from Gene Expression Omnibus (GEO) database. A total of 162 DEGs were identified between 27 TAO samples and 22 health samples from GSE58331, among which six FRGs (CYBB, CTSB, SLC38A1, TLR4, PEX3, and ABCC1) were obtained. The AUC of SLC38A1, TLR4, PEX3 in lacrimal gland tissues was greater than 80 which suggested high diagnostic value in TAO. The result of immune cell infiltrate analysis indicated increased infiltration of monocytes (p < 0.001), macrophages M0(p = 0.039), mast cells activated (p = 0.008), and neutrophils (p = 0.045) in orbital tissues from TAO patients. Meanwhile, mast cells resting (p = 0.043) and macrophages M2 (p = 0.02) showed reduced infiltration in TAO samples. There were no gender differences in immune cell infiltration in the TAO patients. Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs. CYBB-LINC01140-TLR4, CYBB- LINC01140- SLC38A1, TLR4- LINC01140- SLC38A1, and CTSB- ZFHX4-AS1- CYBB may be potential RNA regulatory pathways in TAO. Targeted drugs and transcription factors for differential expressed FRGs were also screened out in our study. In vitro, experiments revealed that CTSB, PEX3, ABCC1 and ZFHX4-AS1(lncRNA) were differentially expressed in orbital fibroblasts (OFs) between TAO groups and healthy controls at the transcriptional level.

Effect of homemade compound microbial inoculum on the reduction of terramycin and antibiotic resistance genes in terramycin mycelial dreg aerobic composting and its mechanism.

In order to tackle the issue of terramycin mycelial dreg (TMD) diagnosis and removal of terramycin and antibiotic resistance genes (ARGs), this study adopted aerobic composting (AC) technology and added homemade compound microbial inoculum (HCMI) to promote the AC of TMD and enhance the removal of terramycin and ARGs. The findings demonstrated that terramycin residue could be basically harmless after AC. Moreover, HCMI not only reduced QacB and tetH but also increased the degradation rates of VanRA, VanT, and dfrA24 by 40.81%, 5.65%, and 54.18%, respectively. The HCMI improved the removal rate of ARG subtypes to a certain extent. According to redundancy analysis, during AC, the succession of the microbial community had a stronger influence on the variance of ARG subtype than the environmental conditions. Differences in the abundance of various bacteria due to changes in temperature may be an intrinsic mechanism for the variation of ARG subtypes.

Research progress and application of artificial intelligence in thyroid associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is a complicated orbitopathy related to dysthyroid, which severely destroys the facial appearance and life quality without medical interference. The diagnosis and management of thyroid-associated ophthalmopathy are extremely intricate, as the number of professional ophthalmologists is limited and inadequate compared with the number of patients. Nowadays, medical applications based on artificial intelligence (AI) algorithms have been developed, which have proved effective in screening many chronic eye diseases. The advanced characteristics of automated artificial intelligence devices, such as rapidity, portability, and multi-platform compatibility, have led to significant progress in the early diagnosis and elaborate evaluation of these diseases in clinic. This study aimed to provide an overview of recent artificial intelligence applications in clinical diagnosis, activity and severity grading, and prediction of therapeutic outcomes in thyroid-associated ophthalmopathy. It also discussed the current challenges and future prospects of the development of artificial intelligence applications in treating thyroid-associated ophthalmopathy.

Constraining the sources and cycling of dissolved inorganic carbon in an alpine river, eastern Qinghai-Tibet Plateau.

It is generally acknowledged that riverine dissolved inorganic carbon (DIC) behaviors play a critical role in global carbon cycling and hence have an impact on climate change. However, little is known about the intricate DIC dynamics under various meteorological conditions in the alpine areas. Here, we investigated DIC biogeochemical processes in the Bailong River catchment, eastern Qinghai-Tibet Plateau (QTP), by combining measurements of major ions, stable and radioactive isotopic compositions of DIC (δ13CDIC and Δ14CDIC), and physiographic parameters in the Bailong River catchment. Statistics and stoichiometry analyses suggest that multiple biogeochemical processes could affect carbon cycling in the Bailong River catchment. The "old" DIC with low Δ14C values (-472.4 ± 127.8 ‰, n = 3) and stoichiometry analysis of dissolved ions showed clear evidence that carbonate weathering is primarily responsible for water chemistry in the upstream (elevation >2000 m). However, upstream samples showed that δ13CDIC increased between 5 ‰ and 11 ‰ from the theoretical mixing line, concomitant with increasing pH and decreasing pCO2, suggesting that isotopic fractionation of DIC due to CO2 outgassing may be the primary cause of the increased δ13CDIC values. Additionally, the higher Δ14C values (-285.4 ± 123.5 ‰, n = 12) in the downstream region below 2000 m suggest that allochthonous modern carbon had a great impact on DIC variations. The presence of younger DIC may have important implications for the interpretation of inorganic carbon age in downstream rivers. Our study demonstrates that physiographic conditions can regulate DIC behaviors, which can improve estimations of carbon yield and comprehension of global carbon cycle.

Are we ready to face the next wave of RSV surge after the COVID-19 Omicron pandemic in China?

Background: China had its first wave of COVID-19 in 2020 and second wave of COVID-19 Omicron in 2022. The number of RSV cases decreased sharply in 2020 and 2022. Investigation of the resurge of RSV infections after the first wave of COVID-19 will guide us to take preventive actions before the resurge of RSV infections after the second wave of COVID-19 Omicron. Methods: We analysed epidemiological and clinical data of 59934 patients with lower respiratory tract infections (LRTI) from a prospective long-term cohort surveillance programme in Suzhou, China, collected from February 2016 to January 2022. The annual incidence of RSV infection in children aged<16 years in 2020 and 2021 was compared with the pre-pandemic years 2016 to 2019. We also compared the clinical characteristics, and RSV-related ICU admissions between pre-pandemic years and 2021. Results: Among children with LRTI, the positive rate of RSV increased by 70.7% in 2021 compared to the average level in the pre-pandemic years. The RSV resurge in 2021 was most prominently in children aged 2-4 years (a significant rise compared with the expected value 149.1%; 95%CI, 67.7% to 378%, P<.01). The percentage of RSV-related ICU admissions decreased in 2021 (3.2% vs 6.7%, P<0.01). The death rate of RSV infections in 2021 was 0.2%, while that in pre-pandemic years was only 0.02%. RSV-associated death in immunocompetent children (complicated by necrotizing encephalitis) was firstly occurred in 2021. Conclusions: Our findings raise concerns for RSV control in Southeast China after the COVID-19 pandemic especially for children aged 2-4 years. Although ICU admissions were significantly reduced in this resurgence, we could not ignore the increase of RSV-associated death.