[Evidence map analysis of randomized controlled trial of commonly used Chinese patent medicines in treatment of type 2 diabetes mellitus in recent five years].

This study systematically combed the randomized controlled trial(RCT) of Chinese patent medicines in treatment of type 2 diabetes mellitus(T2DM) in recent five years by using the method of evidence map. It understood the distribution and quality of evidence in this field and found the existing Chinese patent medicines in treatment of T2DM and the problems in its research. The study collected the commonly used Chinese patent medicines for the treatment of T2DM from three drug catalogs, retrieved Chinese and English databases to obtain RCT literature related to Chinese patent medicines in recent five years, and extracted information such as sample size, study drug, combination medication, course of treatment, and outcome indicators from the literature. It also conducted quality evaluation based on the Cochrane collaborative network bias risk assessment tool and used charts to display the analysis results. A total of 19 kinds of Chinese patent medicines are collected, of which 13 kinds of Chinese patent medicines are mentioned in 131 articles related to RCT. The literature concerning Shenqi Jiangtang Capsules/Granules, Jinlida Granules, and Xiaoke Pills accounts for a large proportion. Outcome indicators include blood glucose, blood lipids, pancreatic islet cell function, and clinical symptoms. In terms of literature quality, 75 articles have correct random methods, and 1 article performs allocation hiding and blind methods. Therefore, the clinical orientation of Chinese patent medicines for the treatment of T2DM is broad, failing to reflect their own characteristics and lacking safety information. Insufficient attention has been paid to TCM syndrome scores, quality of life, and blood lipid outcome indicators that reflect the characteristics of traditional Chinese medicine(TCM). The number of studies on the treatment of T2DM by Chinese patent medicines varies greatly among varieties, and the quality of the studies is low. It is suggested that the holders of the marketing license of T2DM Chinese patent medicines should carry out a post-marketing re-evaluation of the varieties of traditional Chinese patent medicines for treating T2DM according to the relevant requirements of the State Food and Drug Administration, standardize the clinical positioning, and revise and improve the safety information in the instructions. It is recommended that researchers construct a core indicator dataset for Chinese patent medicine treatment of T2DM, improve the efficacy evaluation system, and develop an experimental plan based on CONSORT before conducting RCT.

Neutrophil-Driven M2-Like Macrophages Are Critical for Skin Fibrosis in a Systemic Sclerosis Model.

Systemic sclerosis (SSc) is a challenging autoimmune disease characterized by progressive fibrosis affecting the skin and internal organs. Despite the known infiltration of macrophages and neutrophils, their precise contributions to SSc pathogenesis remain elusive. In this study, we elucidated that CD206hiMHCIIlo M2-like macrophages constitute the predominant pathogenic immune cell population in the fibrotic skin of a bleomycin-induced SSc mouse model. These cells emerged as pivotal contributors to the profibrotic response by orchestrating the production of TGF-ß1 through a MerTK signaling-dependent manner. Notably, we observed that neutrophil infiltration was a prerequisite for accumulation of M2-like macrophages. Strategies such as neutrophil depletion or inhibition of CXCR1/2 were proven effective in reducing M2-like macrophages, subsequently mitigating SSc progression. Detailed investigations revealed that in fibrotic skin, neutrophil-released neutrophil extracellular traps were responsible for the differentiation of M2-like macrophages. Our findings illuminate the significant involvement of the neutrophil-macrophage-fibrosis axis in SSc pathogenesis, offering critical information for the development of potential therapeutic strategies.

Home-based vs center-based exercise on patient-reported and performance-based outcomes for knee osteoarthritis: a systematic review with meta-analysis.

Background: Home-based exercise (HBE) represents an alternative to increase the accessibility of rehabilitation programs and relieve the burden on the health care system for people with knee osteoarthritis. Objectives: To summarize for the first time the effectiveness of HBE as compared to center-based exercise (CBE), both with and without HBE, on patient-reported and performance-based outcomes in people with KOA. Methods: Searches were conducted on PubMed, Cochrane, Embase, Web of Science, and Scopus until March 10, 2023, without date or language restrictions. Randomized controlled trials investigating HBE versus CBE or HBE combined with CBE for people with KOA were eligible. The primary outcomes were patient-reported: pain, physical disability, and quality of life. The secondary outcomes were performance-based: walking ability, lower limb muscle strength, and balance function. Risk of bias was assessed with the Cochrane Risk of Bias tool and quality of evidence according to the GRADE. Results: Eleven trials involving 956 participants were included. There was no difference in short-term pain (SMD, 0.22 [95% CI, -0.04 to 0.47], p = 0.09; I2 = 0%), physical disability (SMD, 0.17 [95% CI, -0.19 to 0.54], p = 0.35; I2 = 0%), walking ability (SMD, -0.21 [95% CI, -0.64 to 0.22], p = 0.33; I2 = 35%) and lower limb muscle strength (SMD, -0.24 [95% CI, -0.88 to 0.41], p = 0.47; I2 = 69%) between HBE and CBE. HBE combined with CBE has better benefits compared with HBE alone in short-term pain (SMD, 0.89 [95% CI, 0.60 to 1.17], p < 0.001; I2 = 11%) and physical disability (SMD, 0.25 [95% CI, 0.00 to 0.50], p = 0.05; I2 = 0%). Conclusion: Based on limited evidence, HBE is as effective as CBE on short-term pain, physical disability, walking ability, and lower limb muscle strength in people with knee osteoarthritis. Furthermore, combining HBE with CBE may enhance the overall efficacy of the intervention. Systematic review registration: PROSPERO, CRD42023416548.

Decoding selectivity: computational insights into AKR1B1 and AKR1B10 inhibition.

Understanding selectivity mechanisms of inhibitors towards highly homologous proteins is of paramount importance in the design of selective candidates. Human aldo-keto reductases (AKRs) pertain to a superfamily of monomeric oxidoreductases, which serve as NADPH-dependent cytosolic enzymes to catalyze the reduction of carbonyl groups to primary and secondary alcohols using electrons from NADPH. Among AKRs, AKR1B1 is emerging as a promising target for cancer treatment and diabetes, despite its high structural similarity with AKR1B10, which leads to severe adverse events. Therefore, it is crucial to understand the selectivity mechanisms of AKR1B1 and AKR1B10 to discover safe anticancer candidates with optimal therapeutic efficacy. In this study, multiple computational strategies, including sequence alignment, structural comparison, Protein Contacts Atlas analysis, molecular docking, molecular dynamics simulation, MM-GBSA calculation, alanine scanning mutagenesis and pharmacophore modeling analysis were employed to comprehensively understand the selectivity mechanisms of AKR1B1/10 inhibition based on selective inhibitor lidorestat and HAHE. This study would provide substantial evidence in the design of potent and highly selective AKR1B1/10 inhibitors in future.

Hydrogen-Bonded Complex of the Parent Phosphinidene.

The diatomic molecule PH is very reactive, and it serves as the parent compound for phosphinidenes featuring a monovalent phosphorus atom. Herein, we report the characterization and reactivity of a rare hydrogen-bonded complex of PH. Specifically, the molecular complex between PH and HCl has been generated by photolysis of chlorophosphine (H2 PCl) at 254 nm in a solid Ar-matrix at 10 K. The IR spectrum of the complex HP⋅⋅⋅HCl and quantum chemical calculations at the UCCSD(T)-F12a/haTZ level consistently prove that the phosphorus atom acts as a hydrogen bond acceptor with a binding energy (D0 ) of -0.6 kcal mol-1 . In line with the observed absorption at 341 nm for the binary complex, the triplet phosphinidene PH undergoes prototype H-Cl bond insertion by reformation of H2 PCl upon photoexcitation at 365 nm. However, this hydrogen-bonded complex is unstable in the presence of N2 and HCl, as both molecules prefers stronger interactions with HCl than PH in the observed complexes HP⋅⋅⋅HCl⋅⋅⋅N2 and HP⋅⋅⋅2HCl.

Polybrominated diphenyl ethers in dust, hair and urine: Exposure, excretion.

Polybrominated diphenyl ethers (PBDEs) have been detected in various environmental media and human tissues. PBDEs concentrations in dust from college buildings and homes and in paired hair and urine samples from students were determined. This is of great significance to explore the accumulation and excretion patterns of PBDEs in the human body. The median PBDEs concentrations in the dust (College: 84.59 ng/g; Home: 170.32 ng/g) and hair (undergraduate: 6.16 ng/g; Home: 3.25 ng/g) samples were generally lower than were found in the majority of previous studies. The PBDEs concentrations in the hair and urine samples were subjected to principal component analysis, and the results combined with the PBDEs detection rates confirmed that hair is a useful non-invasive sampling medium for assessing PBDEs exposure and the risks posed. Body mass indices (BMIs) were used to divide students who had not been exposed to large amounts of PBDEs into groups. Body fat percentage is an important factor affecting the accumulation of PBDE in the human body. Environmental factors were found to affect the PBDEs concentrations in the hair and urine samples less for normal-weight students (BMI≤24) than overweight students (BMI>24). Short-term environmental changes to more readily affect the PBDEs concentrations in the tissues of the normal-weight than overweight students. PBDEs with seven or more bromine substituents were found not to be readily excreted in urine. Performing molecular docking simulations of the binding of isomers BDE-99 and BDE-100 to megalin. The binding energy was higher for BDE-100 and megalin than for BDE-99 and megalin, meaning BDE-99 would be more readily excreted than BDE-100.

Broadband phase noise measurement of single-frequency lasers by the short-fiber recirculating delayed self-heterodyne method.

Characterization of single-frequency lasers (SFLs) requires a precise measurement of their phase noise. However, there exists a contradiction between the frequency range and laser phase noise measurement sensitivity in the delay self-heterodyne method. Achieving a broadband and highly sensitive phase noise measurement often requires overlapping the results obtained from different delay lengths. In this study, we present a precisely designed short-fiber recirculating delayed self-heterodyne (SF-RDSH) method that enables the broadband and highly sensitive laser phase noise measurement in a compact setup. By designing the length of the delay fiber based on a theoretical model, the RDSH technique with a shortest delay length of 200 m enables a highly sensitive laser phase noise measurement from 1 Hz to 1 MHz for the first time, to our knowledge. In the experiment, we demonstrate the broadband phase noise measurement of an SFL by analyzing the 1st and 10th beat notes.

Tripterygium wilfordii Hook.f induced kidney injury through mediating inflammation via PI3K-Akt/HIF-1/TNF signaling pathway: A study of network toxicology and molecular docking.

We intend to explore potential mechanisms of Tripterygium wilfordii Hook.f (TwHF) induced kidney injury (KI) using the methods of network toxicology and molecular docking. We determined TwHF potential compounds with its targets and KI targets, obtained the TwHF induced KI targets after intersecting targets of TwHF and KI. Then we conducted protein-protein interaction (PPI) network, gene expression analysis, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to explore the mechanism of TwHF-induced KI. Finally we conducted molecular docking to verify the core toxic compounds and the targets. We obtained 12 TwHF toxic compounds and 62 TwHF-induced KI targets. PPI network, gene expression analysis and GO function enrichment analysis unveiled the key biological process and suggested the mechanism of TwHF-induced KI might be associated with inflammation, immune response, hypoxia as well as oxidative stress. KEGG pathway enrichment analysis indicated PI3K-Akt signaling pathway, HIF-1 signaling pathway and TNF signaling pathway were key signaling pathways of TwHF induced KI. Molecular docking showed that the binding energy of core targets and toxic compounds was all less than -6.5 kcal/mol that verified the screening ability of network pharmacology and provided evidence for modifying TwHF toxic compounds structure. Through the study, we unveiled the mechanism of TwHF induce KI that TwHF might activate PI3K-Akt signaling pathway as well as TNF signaling pathway to progress renal inflammation, mediate hypoxia via HIF-1 signaling pathway to accelerate inflammatory processes, and also provided a theoretical basis for modifying TwHF toxic compounds structure as well as supported the follow-up research.

New techniques to identify the tissue of origin for cancer of unknown primary in the era of precision medicine: progress and challenges.

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.

In Situ Piezoelectric-Catalytic Anti-Inflammation Promotes the Rehabilitation of Acute Spinal Cord Injury in Synergy.

Relieving inflammation via scavenging toxic reactive oxygen species (ROS) during the acute phase of spinal cord injury (SCI) proves to be an effective strategy to mitigate secondary spinal cord injury and improve recovery of motor function. However, commonly used corticosteroid anti-inflammatory drugs show adverse side effects which may induce increased risk of wound infection. Fortunately, hydrogen (H2), featuring selective antioxidant performance, easy penetrability, and excellent biosafety, is being extensively investigated as a potential anti-inflammatory therapeutic gas for the treatment of SCI. In this work, by a facile in situ growth approach of gold nanoparticles (AuNPs) on the piezoelectric BaTiO3, a particulate nanocomposite with Schottky heterojunction (Au@BT) is synthesized, which can generate H2 continuously by catalyzing H+ reduction through piezoelectric catalysis. Further, theoretical calculations are employed to reveal the piezoelectric catalytic mechanism of Au@BT. Transcriptomics analysis and nontargeted large-scale metabolomic analysis reveal the deeper mechanism of the neuroprotective effect of H2 therapy. The as-prepared Au@BT nanoparticle is first explored as a flexible hydrogen gas generator for efficient SCI therapy. This study highlights a promising prospect of nanocatalytic medicine for disease treatments by catalyzing H2 generation; thus, offering a significant alternative to conventional approaches against refractory spinal cord injury.

Strontium doped Fe-based porous carbon for highly efficient electrocatalytic ORR and MOR reactions.

The catalytic activity improvement of Fe-based active sites derived from metal organic frameworks toward oxygen reduction reaction (ORR) and methanol oxidation reaction (MOR) remains a major challenge. In this study, the growth of strontium decorated 2-methylimidazole zinc salt (Sr/ZIF-8) is prepared as a carrier to vapor deposited iron formation Sr doped Fe-based nitrogen-doped carbon framework (named as Sr/FeNC). After high-temperature pyrolysis and vapor deposition, strontium carbonate nanocrystals are evenly dispersed on the shrunk dodecahedron carbon frame and multitudinous Fe-based active catalytic sites are embedded in carbon skeleton. The optimal Sr/FeNC-2 catalyst demonstrates the outstanding ORR performance in terms of a half-wave potential of 0.851 V and an onset potential of 0.90 V, while Sr/FeNC-2 exhibits a high current density of 18.2 mA cm-2 and a lower Tafel slope of 21 mV dec-1 in MOR. The exceptional catalytic activity could be ascribed to the synergistic coupling effect of strontium compounds with Fe-based catalytic sites (Fe-Nx, Fe, and iron oxide). In particular, the formation of SrCO3 affects the bonding configuration of the iron species sites, leading to an optimization of the electronic structure within the multihole carbon matrix. The synthetic approach presents a prospective strategy for future endeavors in developing innovative and advanced bifunctional catalysts for ORR and MOR.

Structural Design and Analysis of Large-Diameter D30 Conical Polycrystal Diamond Compact (PDC) Teeth under Engineering Rotary Mining Conditions.

In the realm of engineering rotary excavation, the rigid and brittle nature of the Polycrystal Diamond Compact (PDC) layer poses challenges to the impact resistance of conical teeth. This hinders their widespread adoption and utilization. In this paper, the Abaqus simulation is used. By optimizing the parameters of the radius of the cone top arc, we analyzed the changing law of the parameters of large-diameter D30 series conical PDC teeth, such as the equivalent force, impact force, and energy absorption of the conical teeth during the impact process, and optimized the best structure of the conical PDC teeth. After being subjected to a high temperature and high pressure, we synthesized the specimen for impact testing and analyzed the PDC layer crack extension and fracture failure. The findings reveal the emergence of a stress ring below the compacted area of the conical tooth. As the radius of the cone top arc increases, so does the area of the stress ring. When R ≥ 10 mm, the maximum stress change is minimal, and at R = 10 mm, the stress change in its top unit is relatively smooth. Optimal impact resistance is achieved, withstanding a total impact work value of 7500 J. Extrusion cracks appear in the combined layer part of PDC layers I and II, but the crack source is easy to produce in the combined layer of PDC layer II and the alloy matrix and extends to both sides, and the right side extends to the surface of the conical tooth in a "dragon-claw". The failure morphology of the conical teeth includes ring shedding at the top of the PDC layer, the lateral spalling of the PDC layer, and the overall cracking of the conical teeth. Through this study, we aim to promote the popularization and application of large-diameter conical PDC teeth in the field of engineering rotary excavation.

Cell type-specific connectome predicts distributed working memory activity in the mouse brain.

Recent advances in connectomics and neurophysiology make it possible to probe whole-brain mechanisms of cognition and behavior. We developed a large-scale model of the multiregional mouse brain for a cardinal cognitive function called working memory, the brain's ability to internally hold and process information without sensory input. The model is built on mesoscopic connectome data for interareal cortical connections and endowed with a macroscopic gradient of measured parvalbumin-expressing interneuron density. We found that working memory coding is distributed yet exhibits modularity; the spatial pattern of mnemonic representation is determined by long-range cell type-specific targeting and density of cell classes. Cell type-specific graph measures predict the activity patterns and a core subnetwork for memory maintenance. The model shows numerous attractor states, which are self-sustained internal states (each engaging a distinct subset of areas). This work provides a framework to interpret large-scale recordings of brain activity during cognition, while highlighting the need for cell type-specific connectomics.

GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.

Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity.

Neutrophils, accounting for ≈70% of human peripheral leukocytes, are key cells countering bacterial and fungal infections. Neutrophil homeostasis involves a balance between cell maturation, migration, aging, and eventual death. Neutrophils undergo different death pathways depending on their interactions with microbes and external environmental cues. Neutrophil death has significant physiological implications and leads to distinct immunological outcomes. This review discusses the multifarious neutrophil death pathways, including apoptosis, NETosis, pyroptosis, necroptosis, and ferroptosis, and outlines their effects on immune responses and disease progression. Understanding the multifaceted aspects of neutrophil death, the intersections among signaling pathways and ramifications of immunity will help facilitate the development of novel therapeutic methods.

Association of white matter hyperintensities with long-term EGFR-TKI treatment and prediction of progression risk.

PURPOSE: The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and identify clinical risk factors associated with WMH. EXPERIMENTAL DESIGN: This multiple-center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non-small cell lung cancer (NSCLC) who received or did not receive EGFR-TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2-year follow-up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. RESULTS: Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR-TKI and 92 (32%) patients with NSCLC without EGFR-TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR-TKI treatment was independently associated with the WMH progression (EGFR-TKI: aRR 2.72, 95% confidence interval [CI] 1.46-5.06, p = .002). Interleukin (IL)-2, IL-4, and IL-10 were associated with increased WMH in the adjusted model (IL-2: aRR 1.55 [95% CI 1.06-2.25], p = .023; IL-4: aRR 1.66 [95% CI 1.13-2.43], p = .010; IL-10: aRR 1.48 [95% CI 1.06-2.06], p = .020). CONCLUSION: Patients with NSCLC who received EGFR-TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL-2, IL-4, and IL-10 may be used as potential biomarkers to monitor the risk of increased WMH burden.

The Effect of Web-Based Telerehabilitation Programs on Children and Adolescents With Brain Injury: Systematic Review and Meta-Analysis.

BACKGROUND: Acquired brain injury (ABI) in children and adolescents can lead to motor and executive impairments that often require long-term treatment. The implementation of web-based telerehabilitation therapy at home is a method to improve the functional status of patients. Therefore, we performed a systematic review of the effects of web-based telerehabilitation programs on functional outcomes in children and adolescents with brain injury and supplemented the findings with a meta-analysis. OBJECTIVE: This study evaluated the therapeutic effect of web-based telerehabilitation training on children and adolescents with brain injury to determine whether web-based telerehabilitation therapy improved motor function, executive function, physical activity level, lower limb strength, hand and upper limb function, visual processing skills, and occupational functional performance in children and adolescents with brain injury. METHODS: PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched for randomized controlled trials on web-based telerehabilitation programs in children and adolescents with brain injury until December 2022, and the risk of bias was evaluated using the Cochrane Collaboration Tool. Relevant data were extracted, and a meta-analysis was performed using RevMan5.3 software. RESULTS: Overall, 17 studies involving 848 patients were included. Web-based telerehabilitation therapy improved the motor function (standardized mean difference [SMD] 0.29, 95% CI 0.01-0.57; P=.04), physical activity level (SMD 0.42, 95% CI 0.11-0.73; P=.007), lower limb strength (SMD 0.52, 95% CI 0.13-0.90; P=.009), and visual processing skills (SMD 0.26, 95% CI 0.02-0.50; P=.04) of children and adolescents with brain injury. It also improved executive function in letter-number sequencing (SMD 1.26, 95% CI 0.26-2.26; P=.01), attention (SMD 0.38, 95% CI 0.09-0.66; P=.009), and symbol search (SMD 1.18, 95% CI 0.43-1.93, P=.002). CONCLUSIONS: Web-based telerehabilitation therapy improved motor function, physical activity level, lower limb strength, letter-number sequencing, attention, and symbol search, which improved the quality of life in children and adolescents with brain injury. Web-based telerehabilitation programs provide great convenience for children and adolescents with ABI who need long-term treatment and allow them to exercise at home for rehabilitation training. The widespread implementation of remote interventions also provides children and adolescents in remote areas with better access to rehabilitation services. This review provides evidence for the effectiveness of web-based telerehabilitation therapy, but there was heterogeneity in some of the results because of different disease types and intervention programs. Future studies can expand the sample size according to disease type and increase follow-up time according to different exercise prescriptions to further refine the long-term effects of this intervention on various functions of children and adolescents with ABI. TRIAL REGISTRATION: PROSPERO CRD42023421917; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=421917.

Frequency dependent whole-brain coactivation patterns analysis in Alzheimer's disease.

Background: The brain in resting state has complex dynamic properties and shows frequency dependent characteristics. The frequency-dependent whole-brain dynamic changes of resting state across the scans have been ignored in Alzheimer's disease (AD). Objective: Coactivation pattern (CAP) analysis can identify different brain states. This paper aimed to investigate the dynamic characteristics of frequency dependent whole-brain CAPs in AD. Methods: We utilized a multiband CAP approach to model the state space and study brain dynamics in both AD and NC. The correlation between the dynamic characteristics and the subjects' clinical index was further analyzed. Results: The results showed similar CAP patterns at different frequency bands, but the occurrence of patterns was different. In addition, CAPs associated with the default mode network (DMN) and the ventral/dorsal visual network (dorsal/ventral VN) were altered significantly between the AD and NC groups. This study also found the correlation between the altered dynamic characteristics of frequency dependent CAPs and the patients' clinical Mini-Mental State Examination assessment scale scores. Conclusion: This study revealed that while similar CAP spatial patterns appear in different frequency bands, their dynamic characteristics in subbands vary. In addition, delineating subbands was more helpful in distinguishing AD from NC in terms of CAP.

Knowledge mapping and emerging trends of ferroptosis in ischemia reperfusion injury research: A bibliometric analysis (2013-2022).

Objective: Ischemia/reperfusion (I/R) injury is an inevitable dilemma when previously ischemic multiple organs and tissues are returned to a state of blood flow, with confirming a critical role of ferroptosis in molecular, pathway mechanisms, subcellular structure. Discovering the potential relationship may provide useful approaches for the clinical treatment and prognosis of the pathophysiological status of IRI. Therefore, a comprehensive visualization and scientometric analysis were conducted to systematically summarize and discuss the "ferroptosis in ischemia reperfusion injury" research to demonstrate directions for scholars in this field. Methods: We retrieved all publications focusing on I/R injury and ferroptosis from the Web of Science Core Collection (WoSCC), published from 2013 to October 2022. Next, scientometric analysis of different items was performed using various bibliometrics softwares to explore the annual trends, countries/regions, institutions, journals, authors and their multi-dimensional relationship pointing to current hotspots and future advancement in this field. Results: We included a total of 421 English articles in set timespan. The number of publications increased steadily annually. China produced the highest number of publications, followed by the United States. Most publications were from Central South University, followed by Sichuan University and Wuhan University. The most authoritative academic journal was Oxidative Medicine and Cellular Longevity. Cell occupied the first rank of co-cited journal list. Andreas Linkermann and Scott J Dixon may have the highest influence in this intersected field with the highest number of citations and co-cited references respectively. The essential biological reactions such as oxidative stress response, lipid peroxidation metabolism, anti-inflammmatory and pro-inflammatory procedure, and related molecular pathways were knowledge base and current hotspots. Molecules pathways exploration, effective inhibition of I/R injury and promising strategy of improving allografts may become future trends and focuses. Conclusions: Research on ferroptosis in I/R injury had aroused great interest recently. This first bibliometric study comprehensively analyzed the research landscape of ferroptosis and I/R injury, and also provided a reliable reference for related scholars to facilitate further advancement in this field.

TXNIP activates NLRP3/IL-1ß and participate in inflammatory response and oxidative stress to promote deep venous thrombosis.

Increasing evidence indicates that deep venous thrombosis (DVT) is a common peripheral vascular disease. This study aims to investigate the mechanisms of thioredoxin-interacting protein (TXNIP) and nod-like receptor protein 3 (NLRP3) inflammasome in deep venous thrombosis (DVT). A total of 66 Sprague-Dawley (SD) rats were employed to conduct DVT model. DVT rat was treated with silenced TXNIP (si-TXNIP) lentivirus and MCC950 (a NLRP3 inhibitor). The thrombosis weight and weight/length ratio, tissue factor, inflammatory factors, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were measured. Hematoxylin-eosin (H&E) staining was used to investigate the pathological change. Western blotting was used to determine the protein expression level. The expression level of thioredoxin (TRx) was suppressed, whereas TXNIP and NLRP3 were elevated in DVT rat. Si-TXNIP or MCC950 could reduce the thrombosis weight and weight/length ratio, ameliorate the pathological change, and decrease inflammatory reaction. Mechanistically, si-TXNIP or MCC950 inhibited the expression levels of TXNIP, NLRP3, and interleukin (IL)-1ß while elevating the TRx level, thereby suppressing the DVT. Our study indicated that si-TXNIP or MCC950 injection rescued the injury of vein induced by DVT. The possible mechanisms connected with the inhibition of TXNIP and NLRP3. TXNIP is a possible therapeutic target for DVT.