Artemisia argyi polyphenols Attenuates DSS-induced colitis in mice by regulating the structural composition of gut microbiota.

BACKGROUND: Intestinal health is affected by heredity, lifestyle, and structure of gut microbiota. The imbalance of symbiotic and harmful bacteria in gut microbiota may increase the occurrence of colonic inflammation. Supplementary A. muciniphila can improve the survival rate of colitis mice, reduce colon tissue injury, and the expression of anti-inflammatory factors was upregulated. Artemisia argyi has been reported to have anti-inflammatory, antioxidant, bactericidal, and immunomodulatory effects. However, its anti-inflammatory effect and mechanism, and its influence on gut microbiota and metabolites are still unclear yet. PURPOSE: To explore whether Artemisia argyi Polyphenols(AAPs) can alleviate ulcerative colitis (UC) by changing gut microbiota. METHODS: The therapeutic effect of AAPs on colitis was investigated by inducing ulcerative colitis in mice using dextran sodium sulfate (DSS) and administering different doses of AAPs orally to mice. Exploring the levels of inflammatory proteins, oxidative stress proteins, and barrier proteins using western blotting and immunofluorescence, and explored the structural changes of gut microbiota and its metabolites. Meanwhile, in order to explore whether the role of AAPs in alleviating colitis is based on the regulation of gut microbiota structure, we conducted fecal microbiota transplantation (FMT). RESULTS: It showed that AAPs and FMT trial alleviated DSS-induced colonic injury, including clinical parameters and pathological injury of colon tissue, reduction in the expression of inflammatory proteins: IL-6, TNF-α, p-p65, p-IκBα, and increase in the expression of antioxidant proteins: Nrf2, NQO-1 and HO-1 and barrier proteins: Claudin-1, Occludin, ZO-1 and MUC2. AAPs and FMT promoted the content of beneficial bacteria, such as Butyricimonas and Lactobacillus, and the content of beneficial metabolites for instance acetic acid, butyric acid, and valeric acid has also increased. CONCLUSION: These results suggested that AAPs might improve DSS-induced colonic injury by changing the structural of gut microbiota while promoting the synthesis of fatty acids in the intestine, thereby providing a theoretical basis for using AAPs to treat ulcerative colitis.

Aberrant individual structure covariance network in patients with mesial temporal lobe epilepsy.

Objective: Mesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural covariance network (SCN) could reveal the structural connectivity disruption of the mTLE but could not reflect the heterogeneity at the individual level. Methods: This study adopted a recently proposed individual structural covariance network (IDSCN) method to clarify the alternated structural covariance connection mode in mTLE and to associate IDSCN features with the clinical manifestations and regional brain atrophy. Results: We found significant IDSCN abnormalities in the ipsilesional hippocampus, ipsilesional precentral gyrus, bilateral caudate, and putamen in mTLE patients than in healthy controls. Moreover, the IDSCNs of these areas were positively correlated with the gray matter atrophy rate. Finally, we identified several connectivities with weak associations with disease duration, frequency, and surgery outcome. Significance: Our research highlights the role of hippo-thalamic-basal-cortical circuits in the pathophysiologic process of disrupted whole-brain morphological covariance networks in mTLE, and builds a bridge between brain-wide covariance network changes and regional brain atrophy.

Forsythiaside A attenuates lipopolysaccharide-induced mouse mastitis by activating autophagy and regulating gut microbiota and metabolism.

Mastitis is an inflammatory disease of the mammary gland with a high incidence in lactating animals, significantly impacting their health and breastfeeding. Moreover, mastitis adversely affects milk quality and yield, resulting in substantial economic losses for the dairy farming industry. Forsythiaside A (FTA), a phenylethanol glycoside analog extracted from Forsythia, exhibits notable anti-inflammatory and antioxidant properties. However, its protective effects and specific mechanisms against mastitis remain unclear. In this study, a lipopolysaccharide (LPS)-induced mouse mastitis model was used to investigate the protective effect of FTA on LPS-induced mastitis and its potential mechanism using histological assays, Western blot, qRT-PCR, FITC-albumin permeability test, 16s rRNA gene sequencing analysis and non-targeted metabolomics assays to investigate the protective effect of FTA on LPS-induced mastitis model and its potential mechanism. The results demonstrated that FTA significantly mitigated LPS-induced mouse mastitis by reducing inflammation and apoptosis levels, modulating the PI3K/AKT/mTOR signaling pathways, inducing autophagy, and enhancing antioxidant capacity and the expression of tight junction proteins. Furthermore, FTA increased the abundance of beneficial microbiota while decreasing the levels of harmful microbiota in mice, thus counteracting the gut microbiota disruption induced by LPS stimulation. Intestinal metabolomics analysis revealed that FTA primarily regulated LPS-induced metabolite alterations through key metabolic pathways, such as tryptophan metabolism. This study confirms the anti-inflammatory and antioxidant effects of FTA on mouse mastitis, which are associated with key metabolic pathways, including the restoration of gut microbiota balance and the regulation of tryptophan metabolism. These findings provide a novel foundation for the treatment and prevention of mammalian mastitis using FTA.

Transcriptome sequencing analysis of bovine mammary epithelial cells induced by lipopolysaccharide.

Mastitis in cows is caused by the inflammation of the mammary glands due to an infection by external pathogenic bacteria. Mammary gland epithelial cells, which are in direct contact with the external environment, are responsible for the first line of defense of the mammary gland against pathogenic bacteria, playing an essential role in immune defense. To investigate the mechanism of bovine mammary epithelial cells in the inflammatory process, we treated the cells with LPS for 12 hours and analyzed the changes in mRNA by transcriptome sequencing. The results showed that compared to the control group, the LPS treatment group had 121 up-regulated genes and 18 down-regulated genes. GO and KEGG enrichment analysis revealed that these differential genes were mainly enriched in the IL-17 signaling pathway, Legionellosis, Cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and other signaling pathways. Furthermore, the expression of GRO1 and CXCL3 mRNAs increased significantly after LPS treatment. These findings provide new insights for the treatment of mastitis in cows in the future.

Esculetin improves murine mastitis induced by streptococcus isolated from bovine mammary glands by inhibiting NF-κB and MAPK signaling pathways.

Cow mastitis, caused by Streptococcus infection of the mammary glands, is a common clinical disease that can lead to decreased milk quality and threaten animal welfare and performance. Esculetin (ESC) is a coumarin with anti-inflammatory and anti-asthmatic effects. However, whether ESC has therapeutic effects on mastitis remains unexplored. This study was conducted to investigate the protective effect of ESC against murine mastitis caused by Streptococcus isolated from bovine mammary glands and elucidate the underlying mechanisms. Streptococcus uberis was used to construct a mouse model of mastitis. The results showed that the mice exhibited edema and thickening of the acinar wall with inflammatory infiltration after S. uberis treatment. Intraperitoneal injection of ESC significantly reduced inflammatory cell infiltration, restored normal physiological function, and inhibited the production of the inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analysis revealed that ESC reduced P38 phosphorylation, further inhibited the influence of mammary Streptococcus on cytoplasmic translocation of nuclear factor-κB (P65), and inhibited the transcriptional activation of P65, thus inhibiting the generation of inflammatory cells. Collectively, ESC may inhibit mitogen-activated protein kinase and nuclear factor-κB, thereby highlighting its potential for the treatment and prevention of mastitis.

Transcriptomic profiling of lipopolysaccharide-challenged bovine mammary epithelial cells treated with forsythoside A.

Mastitis is usually caused by a variety of pathogenic bacteria that seriously impact the health and milk-production ability of dairy cows, with consequent, economically detrimental effects on the dairy industry. Forsythoside A (FTA), isolated from the fruit and leaves of Forsythia suspensa (Thunb.) Vahl (Oleaceae), has been reported to have significant antioxidant, anti-inflammatory, and antibacterial effects. However, it is not clear whether FTA exerts a protective effect against lipopolysaccharide (LPS)-induced bovine mastitis and its potential gene signature. In this study, high-throughput sequencing technology was performed to analyze the differences between the mRNA and enrichment pathway of bovine mammary epithelial cells of the control, LPS, and LPS + FTA groups. The results showed that there were 139 differentially expressed genes (DEGs) (p-value < 0.05, |log2FoldChange| > 1, FPKM > 1) in the LPS group compared with the control group, including 121 up-regulated genes and 18 down-regulated genes, which were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity, protein binding, and IL-17 signaling pathway based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, respectively. Compared with the control group and LPS + FTA group, there were 349 DEGs, including 322 up-regulated genes and 27 down-regulated genes. They were mainly enriched in protein localization to organelles, centrosomes, binding, and the IL-17 signaling pathway, based on GO and KEGG analysis. Compared to the LPS group, the LPS + FTA group had 272 DEGs, including 259 up-regulated genes and 13 down-regulated genes, which were mainly enriched in RNA processing, IL-6 receptor binding, and the lysosome pathway, based on GO and KEGG analyses. It can be seen that LPS stimulation induced the expression of inflammation-related genes, IL-17 and IL-6, whereas FTA treatment promoted the expression of the spliceosome-, lysosome-, and oxidative stress-related genes HSP70, HSPA8, and PARP2. The study utilized RNA-sequencing analysis of FTA against LPS-challenged bovine mammary epithelial cells to explore key mRNA findings that may be strongly associated with inflammation and oxidative stress, and provides a theoretical reference for further elucidation of molecular mechanisms of bovine mastitis and therapeutic effects of FTA against bovine mastitis.

Optimized SEEG-guided three-dimensional radiofrequency thermocoagulation for insular epilepsy.

PURPOSE: The high risk of resection surgery for drug-resistant insular epilepsy has driven interest in new treatment techniques. Stereo-electroencephalography-guided three-dimensional radiofrequency thermocoagulation (SEEG-3D RFTC) offers an alternative option. Herein, we present the detailed protocol and investigation of the efficacy and safety of a preliminary observational study. METHODS: From February 2017 to April 2021, ten patients diagnosed with insular epilepsy were enrolled in the study. They underwent implantation of a combination of SEEG electrodes to form a high-density focal stereo-array in insula, including oblique electrodes through the long axis of insula and orthogonal electrodes to widely cover the medial and lateral insula. SEEG-3D RFTC was performed between two contiguous contacts of the same electrode, or between two adjacent contacts of different electrodes. RESULTS: Surgical procedures were well tolerated, with no related long-term complications. Seizure-free outcome was achieved in seven patients (70%), including ILAE I in four and ILAE II in three. Two other (20%) patients had rare seizures (ILAE III). One (10%) patient experienced an ILAE IV outcome (follow-up = 12--63 months). The responder rate (including ILAE I-IV) was 100%. CONCLUSION: The optimized SEEG-3D RFTC is an effective and safe option for the treatment of drug-resistant insular epilepsy.

The role of the orbitofrontal cortex and insula for prognosis of mesial temporal lobe epilepsy.

OBJECTIVE: We investigated the network between the medial temporal lobe (MTL) and extratemporal structures in patients with mesial temporal lobe epilepsy (MTLE) in order to explain the recurrence of MTLE after surgery. This study contributes to our current understanding of MTLE with stereotactic electroencephalography (SEEG). METHODS: We conducted a retrospective study of SEEG in 20 patients with MTLE in order to observe and analyze the intensity of interictal high-frequency oscillations (HFOs), as well as the dynamic course of coherence connectivity values of the MTL and extratemporal structures during the initial phase of the seizure. The results correlated with the patient prognosis. RESULTS: First, the presence of HFOs was observed during the interictal period in all 20 patients; these were localized to the MTL in 17 patients and the orbitofrontal cortex in seven patients and the insula in six patients. The better the prognosis, the greater the localization of the HFOs concentration in the MTL structures (p < 0.05). Second, significantly enhanced connectivity of MTL structures with the orbitofrontal cortex and insula was observed in most patients with MTLE, before and after the seizure onset (p < 0.05). Finally, the connectivity between extratemporal structures, such as the orbitofrontal cortex and insula, and MTL structures was significantly stronger in patients who had a worse prognosis than in other patients, before and after seizure onset (p < 0.05). INTERPRETATION: The epileptogenic network in recurrent MTLE is not limited to MTL structures but is also associated with the orbitofrontal cortex and insula. This can be used as a potential indicator for predicting the prognosis of patients after surgery, providing an important avenue for future clinical evaluation.

Correction: In-chain functionalized syndiotactic 1,2-polybutadiene by a Ziegler-Natta iron(iii) catalytic system.

[This corrects the article DOI: 10.1039/C9RA06499K.].

Mapping Intellectual Structures and Research Hotspots of Triple Negative Breast Cancer: A Bibliometric Analysis.

BACKGROUND: Triple negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with a poor prognosis due to its extremely aggressive nature and lack of effective treatment options. This study aims to summarize the current hotspots of TNBC research and evaluate the TNBC research trends, both qualitatively and quantitatively. METHODS: Scientific publications of TNBC-related studies from January 1, 2010 to October 17, 2020 were obtained from the Web of Science database. The BICOMB software was used to obtain the high-frequency keywords layout. The gCLUTO was used to produce a biclustering analysis on the binary matrix of word-paper. The co-occurrence and collaboration analysis between authors, countries, institutions, and keywords were performed by VOSviewer software. Keyword burst detection was performed by CiteSpace. RESULTS: A total of 12,429 articles related to TNBC were identified. During 2010-2020, the most productive country/region and institution in TNBC field was the USA and The University of Texas MD Anderson Cancer Center, respectively. Cancer Research, Journal of Clinical Oncology, and Annals of Oncology were the first three periodicals with maximum publications in TNBC research. Eight research hotspots of TNBC were identified by co-word analysis. In the core hotspots, research on neoadjuvant chemotherapy, paclitaxel therapy, and molecular typing of TNBC is relatively mature. Research on immunotherapy and PARP inhibitor for TNBC is not yet mature but is the current focus of this field. Burst detection of keywords showed that studies on TNBC proteins and receptors, immunotherapy, target, and tumor cell migration showed bursts in recent three years. CONCLUSION: The current study revealed that TNBC studies are growing. Attention should be paid to the latest hotspots, such as immunotherapy, PARP inhibitors, target, and TNBC proteins and receptors.

Novel Double Endobutton Technique Combined with Three-Dimensional Printing: A Biomechanical Study of Reconstruction in Acromioclavicular Joint Dislocation.

OBJECTIVE: To reconstruct the acromioclavicular (AC) joint using an adjusted closed-loop double Endobutton technique via a guiding locator that was applied using three-dimensional (3D) printing technology. At the same time, the reliability and safety of the novel double Endobutton (NDE) were tested by comparing the biomechanics of this technique with the TightRope (TR) approach. METHODS: This retrospective study was conducted between January 2017 and January 2019. The Department of Anatomy at Southern Medical University obtained 18 fresh-frozen specimens (8 left and 10 right; 12 men and 6 women). First, the guiding locators were applied using 3D printing technology. After preparation of materials, specimens were divided into an NDE group, a TR group, and a normal group. In the NDE and TR groups, the navigation module was used to locate and establish the bone tunnels; after that, the NDE or TR was implanted. However, the Endobuttons were fixed while pressing the distal clavicle downwards and the length of the loop could be adjusted by changing the upper Endobutton in the NDE group while the suture button construct was tensioned and knotted after pressing down the distal clavicle in the TR. Finally, load testing in anterior-posterior (AP), superior-inferior (SI), and medial-lateral (ML) directions as well as load-to-failure testing in the SI direction were undertaken to verify whether the NDE or TR had better biomechanics. RESULTS: In the load testing, the displacements of the NDE and TR groups in the AP, SI, and ML direction were significantly shorter than those of the normal group (P < 0.05). In the load-to-failure testing, the ultimate load of the NDE and TR groups had significantly higher increases than the normal group (722.16 ± 92.04 vs 564.63 ± 63.05, P < 0.05; 680.20 ± 110.29 vs 564.63 ± 63.05, P < 0.05). However, there was no statistically significant difference between the two techniques for these two tests (P > 0.05). In the NDE group, four of six failures were a result of tunnel fractures of the coracoid, while two of six were due to suture breakage. In the TR, three failures were due to coracoid tunnel fractures, one was a result of a clavicle tunnel fracture, and the rest were due to suture breakage. In the normal group, half of the failures were a result of avulsion fractures of the conical ligament at the point of the coracoid process, and the other three were due to rupture of the conical ligament, fracture of the distal clavicle, and fracture of the scapular body. CONCLUSION: As for the TR technique, the stability and strength of the AC joint were better in patients who underwent reconstruction using the NDE technique than in the intact state.

Electrophysiological properties and seizure networks in hypothalamic hamartoma.

OBJECTIVE: Little is known about the intrinsic electrophysiological properties of hypothalamic hamartoma (HH) in vivo and seizure network since only few cases using stereoelectroencephalography (SEEG) electrodes exploring both cortex and HH have been published. To elucidate these issues, we analyzed simultaneous SEEG recordings in HH and cortex systematically. METHODS: We retrospectively investigated data from 15 consecutive patients with SEEG electrodes into the HH for the treatment purpose of radiofrequency thermocoagulation treatment. Additional SEEG electrodes were placed into the cortex in 11 patients to assess extra-HH involvement. Interictal discharges within the HH and anatomo-electroclinical correlations during seizures of each patient were qualitatively and quantitatively analyzed. RESULTS: Overall, 77 electrodes with 719 contacts were implanted, and 33 spontaneous seizures were recorded during long-term SEEG monitoring. Interictally, distinct electrophysiological patterns, including isolated intermittent spikes/sharp waves, burst spike and wave trains, paroxysmal fast discharges, periodic discharges, and high-frequency oscillations, were identified within the HH. Notably, synchronized or independent interictal discharges in the cortex were observed. Regarding the ictal discharges, the electrical onset pattern within the HH always started with abrupt giant shifts superimposed on low-voltage fast activity across patients. The gelastic seizure network mainly involved the HH, orbitofrontal areas, and cingulate gyrus. Seizures with automatisms and impaired awareness primarily propagated to mesial temporal lobes. Moreover, independent ictal discharges arising from the mesial temporal lobe were detected in three out of nine patients. INTERPRETATION: This study comprehensively reveals intrinsic electrophysiological patterns and epileptogenic networks in vivo, providing new insights into the mechanisms underlying cortical and subcortical epileptogenesis.

Automatic labeling of the fanning and curving shape of Meyer's loop for epilepsy surgery: an atlas extracted from high-definition fiber tractography.

BACKGROUND: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time. METHODS: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients). RESULTS: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively. CONCLUSION: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.

Cutting Performance Evaluation of the Coated Tools in High-Speed Milling of AISI 4340 Steel.

The cutting performance of cutting tools in high-speed machining (HSM) is an important factor restricting the machined surface integrity of the workpiece. The HSM of AISI 4340 is carried out by using coated tools with TiN/TiCN/TiAlN multi-coating, TiAlN + TiN coating, TiCN + NbC coating, and AlTiN coating, respectively. The cutting performance evaluation of the coated tools is revealed by the chip morphology, cutting force, cutting temperature, and tool wear. The results show that the serration and shear slip of the chips become more clear with the cutting speed. The lower cutting force and cutting temperature are achieved by the TiN/TiCN/TiAlN multi-coated tool. The flank wear was the dominant wear form in the milling process of AISI 4340. The dominant wear mechanisms of the coated tools include the crater wear, coating chipping, adhesion, abrasion, and diffusion. In general, a TiN/TiCN/TiAlN multi-coated tool is the most suitable tool for high-speed milling of AISI 4340, due to the lower cutting force, the lower cutting temperature, and the high resistance of the element diffusion.

In-chain functionalized syndiotactic 1,2-polybutadiene by a Ziegler-Natta iron(iii) catalytic system.

Copolymerization of 1,3-butadiene with four 1-substituted 1,3-diene comonomers bearing amino and alkyoxy groups by a Ziegler-Natta iron(iii) catalytic system to access in-chain functionalized syndiotactic 1,2-polybutadiene is reported herein. The polar comonomer content can be easily regulated by varying the comonomer loadings or polymerization conditions, affording functionalized syndiotactic 1,2-polybutadiene with different amounts of functionalities. The incorporation of a polar comonomer showed little influence on the 1,2-content and stereoregularity of the resulting polymers, giving a 1,2-structure as high as ∼85% and an rrrr pentad of 81.0%. Significantly improved surface properties of the polymers was obtained after incorporation of polar comonomer, as revealed from the remarkably decreased water contact angles.

Health effects of manganese exposures for welders in Qingdao City, China.

OBJECTIVES: To document if manganese from welding causes health effects including neurological symptoms associated with manganese exposure. MATERIAL AND METHODS: An anonymous questionnaire survey for a total of 505 welders at 3 welding facilities in Qingdao City, China was administered and analyzed. RESULTS: Numerous symptoms were reported by the welders including difficulty with eyes for 43% of them, sore throat for 30% of them, and tremors were reported by over 18% of them. Tremors were associated with longer periods of work as a welder and correlated with the relative cleanliness at the 3 different facilities. Tremors did not correlate with smoking. CONCLUSIONS: Manganese-exposed welders reported a variety of symptoms related to work and showed neurological disturbances that correlated with amount of exposure. Int J Occup Med Environ Health 2017;30(2):241-247.