Gibberellic acid targeting ZBTB16 reduces NF-κB dependent inflammatory stress in sepsis-induced neuroinflammation.

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.

Roles Played by DOCK11, a Guanine Nucleotide Exchange Factor, in HBV Entry and Persistence in Hepatocytes.

HBV infection is challenging to cure due to the persistence of viral covalently closed circular viral DNA (cccDNA). The dedicator of cytokinesis 11 (DOCK11) is recognized as a guanine nucleotide exchange factor (GEF) for CDC42 that has been reported to be required for HBV persistence. DOCK11 is expressed in both the cytoplasm and nucleus of human hepatocytes and is functionally associated with retrograde trafficking proteins Arf-GAP with GTPase domain, ankyrin repeat, and pleckstrin homology domain-containing protein 2 (AGAP2), and ADP-ribosylation factor 1 (ARF1), together with the HBV capsid, in the trans-Golgi network (TGN). This opens an alternative retrograde trafficking route for HBV from early endosomes (EEs) to the TGN and then to the endoplasmic reticulum (ER), thereby avoiding lysosomal degradation. DOCK11 also facilitates the association of cccDNA with H3K4me3 and RNA Pol II for activating cccDNA transcription. In addition, DOCK11 plays a crucial role in the host DNA repair system, being essential for cccDNA synthesis. This function can be inhibited by 10M-D42AN, a novel DOCK11-binding peptide, leading to the suppression of HBV replication both in vitro and in vivo. Treatment with a combination of 10M-D42AN and entecavir may represent a promising therapeutic strategy for patients with chronic hepatitis B (CHB). Consequently, DOCK11 may be seen as a potential candidate molecule in the development of molecularly targeted drugs against CHB.

Effects of motor and cognitive complex training on obstacle walking and brain activity in people with Parkinson's disease: a randomized controlled trial.

BACKGROUND: The difficulties in obstacle walking are significant in people with Parkinson's disease (PD) leading to an increased fall risk. Effective interventions to improve obstacle walking with possible training-related neuroplasticity changes are needed. We developed two different exercise programs, complex walking training and motor-cognitive training, both challenging motor and cognitive function for people with PD to improve obstacle walking. AIM: To investigate the effects of these two novel training programs on obstacle walking and brain activities in PD. DESIGN: A single-center randomized, single-blind controlled study. SETTING: University laboratory; outpatient. POPULATION: Individuals with idiopathic PD. METHODS: Thirty-two participants were randomly assigned to the complex walking training group (N.=11), motor-cognitive training group (N.=11) or control group (N.=10). Participants in training groups received exercises for 40 minutes/session, with a total of 12-session over 6 weeks. Control group did not receive additional training. Primary outcomes included obstacle walking, and brain activities (prefrontal cortex (PFC), premotor cortex (PMC), and supplementary motor area (SMA)) during obstacle walking by using functional near-infrared spectroscopy. Secondary outcomes included obstacle crossing, timed up and go test (TUG), cognitive function in different domains, and fall efficacy scale (FES-I). RESULTS: The motor-cognitive training group demonstrated greater improvements in obstacle walking speed and stride length, SMA activity, obstacle crossing velocity and stride length, digit span test, and TUG than the control group. The complex walking training did not show significant improvement in obstacle walking or change in brain activation compared with control group. However, the complex walking training resulted in greater improvements in Rey-Osterrieth Complex Figure test, TUG and FES-I compared with the control group. CONCLUSIONS: Our 12-session of the cognitive-motor training improved obstacle walking performance with increased SMA activities in people with PD. However, the complex walking training did not lead such beneficial effects as the cognitive-motor training. CLINICAL REHABILITATION IMPACT: The cognitive-motor training is suggested as an effective rehabilitation program to improve obstacle walking ability in individuals with PD.

NOD2 contributes to Parvimonas micra-induced bone resorption in diabetic rats with experimental periodontitis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide-binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. METHODS: We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high-throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro-computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin-12 (IL-6) were detected by western blot. RESULTS: The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL-6. CONCLUSIONS: The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas.

Abundances of Neutron-capture Elements in 62 Stars in the Globular Cluster Messier 15.

M15 is a globular cluster with a known spread in neutron-capture elements. This paper presents abundances of neutron-capture elements for 62 stars in M15. Spectra were obtained with the Michigan/Magellan Fiber System spectrograph, covering a wavelength range from ∼4430 to 4630 Å. Spectral lines from Fe i, Fe ii, Sr i, Zr ii, Ba ii, La ii, Ce ii, Nd ii, Sm ii, Eu ii, and Dy ii were measured, enabling classifications and neutron-capture abundance patterns for the stars. Of the 62 targets, 44 are found to be highly Eu-enhanced r-II stars, another 17 are moderately Eu-enhanced r-I stars, and one star is found to have an s-process signature. The neutron-capture patterns indicate that the majority of the stars are consistent with enrichment by the r-process. The 62 target stars are found to show significant star-to-star spreads in Sr, Zr, Ba, La, Ce, Nd, Sm, Eu, and Dy, but no significant spread in Fe. The neutron-capture abundances are further found to have slight correlations with sodium abundances from the literature, unlike what has been previously found; follow-up studies are needed to verify this result. The findings in this paper suggest that the Eu-enhanced stars in M15 were enhanced by the same process, that the nucleosynthetic source of this Eu pollution was the r-process, and that the r-process source occurred as the first generation of cluster stars was forming.

Electrical acupoint stimulation for the treatment of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

Background: Chemotherapy-induced nausea and vomiting (CINV) is the most common adverse effect of chemotherapy and affects the continuation of chemotherapy in cancer patients. Electrical acupoint stimulation (EAS), which includes electroacupuncture and transcutaneous electrical stimulation (TES), has been used to treat CINV. This meta-analysis aimed to evaluate the efficacy of EAS in the treatment of CINV. Methods: Randomized controlled trials (RCTs) of EAS for CINV retrieved form five key databases. Two researchers independently performed article screening, data extraction and data integration. The Cochrane Collaboration's tool for assessing risk of bias was used to assesse the methodological quality according to Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.4 was used to perform analyses. Results: 10 RCTs with a total of 950 participants were included. The results showed that there was no significant difference between EAS compared to sham EAS in terms of increasing the rate of complete control of CINV and decreasing the overall incidence of CINV [RR = 1.26, 95 % CI (0.96, 1.66), P = 0.95; RR = 1.16, 95 % CI (0.97, 1.40), p = 0.71]. In terms of CINV severity, EAS reduced the occurrence of moderate-to-severe CINV [RR = 0.60, 95 % CI (0.38, 0.94), P = 0.03; RR = 0.50, 95 % CI (0.33, 0.76), P = 0.001]. Conclusion: EAS could improve moderate-to-severe CINV. However, EAS did not show a significant difference in reducing overall incidence and improving complete control rates compared with sham EAS. Due to limitations in the quality of the included articles, the available studies are insufficient to have sufficient evidence to confirm the efficacy of EAS for CINV. Validation with rigorously designed, large-sample, high-quality clinical trial studies may also be needed.

[Advances in the Effects of Microplastics on Soil N2O Emissions and Nitrogen Transformation].

Research on microplastics (MPs) is gaining more attention in the soil environment, but their impact on soil microbiota and related nitrogen processes remains poorly understood. Nitrous oxide (N2O) is one of the important greenhouse gases of the nitrogen cycle in agricultural soil, which mainly originates from microbial-mediated nitrogen (N) transformation processes. Microplastics can influence soil nitrogen transformation, as well as nitrogen-related functional enzymes and genes, and its enrichment may profoundly affect the N2O emissions in soil. However, because of the complexity of the properties of MPs, variations in experimental conditions, and spatial-temporal scales, the results on the effects of MPs on soil N2O emissions, nitrogen content, enzymes activities, and nitrogen functional genes remain inconsistent. Additionally, there is a lack of research conducted at broader experimental scales (e.g., pot scale), from diverse perspectives (e.g., denitrification or DNRA), and using advanced techniques (e.g., stable isotope approaches) to elucidate the underlying mechanisms. Therefore, to comprehend the environmental risk of MPs on soil from multiple perspectives, this review summarized the impact of MPs on soil N cycling from previous published research to provide a knowledge basis and gain holistic insights into the potential impact of soil microplastic enrichment on N2O emission patterns in agricultural soils under climate change conditions.

Genomic characterization and outbreak investigations of methicillin-resistant Staphylococcus aureus in a county-level hospital in China.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen contributing to healthcare-associated infections, which can result in multiple sites infections. The epidemiological characteristics of MRSA exhibit variability among distinct regions and healthcare facilities. The aim of this study was to investigate the molecular epidemiology and nosocomial outbreak characteristics of MRSA in a county-level hospital in China. A total of 130 non-repetitive MRSA strains were collected from December 2020 to November 2021. Whole-genome sequencing (WGS) was performed to identify antimicrobial resistance and virulence factors. Phylogenetic analysis was conducted to ascertain genetic diversity and phylogenetic relationships. Independent transmission scenarios were determined by the phylogeny derived from single nucleotide polymorphisms (SNPs) within the core genome. All the MRSA isolates were collected from the intensive care unit (30.00%, 39/130), the department of otorhinolaryngology (10.00%, 13/130) and the department of burn unit (9.23%, 12/130). The clinical samples mainly included phlegm (53.85%, 70/130), purulent fluid (24.62%, 32/130), and secretions (8.46%, 11/130). The resistance rates to erythromycin, clindamycin and ciprofloxacin were 75.38, 40.00, and 39.23%, respectively. All the isolates belonged to 11 clonal complexes (CCs), with the major prevalent types were CC5, CC59, and CC398, accounting for 30.00% (39/130), 29.23% (38/130), and 16.92% (22/130), respectively. Twenty sequence types (STs) were identified, and ST59 (25.38%, 33/130) was the dominant lineage, followed by ST5 (23.84%, 31/130) and ST398 (16.92%, 22/130). Three different SCCmec types were investigated, most of isolates were type IV (33.85%, 44/130), followed by type II (27.69%, 36/130) and type III (0.77%, 1/130). The common clonal structures included CC5-ST5-t2460-SCCmec IIa, CC59-ST59-t437-SCCmec IV and CC398-ST398-t034-SCCmec (-), with rates of 16.92% (22/130), 14.62% (19/130), and 13.84% (18/130), respectively. Only 12 panton-valentine leucocidin (PVL) positive strains were identified. Two independent clonal outbreaks were detected, one consisting of 22 PVL-negative strains belongs to CC5-ST5-t2460-SCCmec IIa and the other consisting of 8 PVL-negative strains belongs to CC5-ST5-t311-SCCmec IIa. Overall, our study indicated that the CC5 lineage emerged as the predominant epidemic clone of MRSA, responsible for nosocomial outbreaks and transmission within a county-level hospital in China, highlighting the necessity to strengthen infection control measures for MRSA in such healthcare facilities.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Clinical efficacy of tumor organoid-guided cancer therapy for locally advanced unresectable or metastatic breast cancer.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

The application of electrical impedance tomography and surgical outcomes of thoracoscope-assisted surgical stabilization of rib fractures in severe chest trauma.

Serious blunt chest trauma usually induces hemothorax, pneumothorax, and rib fractures. More studies have claimed that early video-assisted thoracoscopic surgery with surgical stabilization of rib fractures (SSRF) results in a good prognosis in patients with major trauma. This study aimed to verify the outcomes in patients with chest trauma whether SSRF was performed. Consecutive patients who were treated in a medical center in Taiwan, for traumatic events between January 2015 and June 2020, were retrospectively reviewed. This study focused on patients with major trauma and thoracic injuries, and they were divided into groups based on whether they received SSRF. We used electrical impedance tomography (EIT) to evaluate the change of ventilation conditions. Different scores used for the evaluation of trauma severity were also compared in this study. Among the 8396 patients who were included, 1529 (18.21%) had major trauma with injury severity score > 16 and were admitted to the intensive care unit initially. A total of 596 patients with chest trauma were admitted, of whom 519 (87%) survived. Younger age and a lower trauma score (including injury severity scale, new injury severity score, trauma and injury severity score, and revised trauma score) account for better survival rates. Moreover, 74 patients received SSRF. They had a shorter intensive care unit (ICU) stay (5.24, p = 0.045) and better performance in electrical impedance tomography (23.46, p < 0.001). In patients with major thoracic injury, older age and higher injury survival scale account for higher mortality rate. Effective surgical stabilization of rib fractures shortened the ICU stay and helped achieve better performance in EIT. Thoracoscope-assisted rib fixation is suggested in severe trauma cases.

HFM-Tracker: a cell tracking algorithm based on hybrid feature matching.

Cell migration is known to be a fundamental biological process, playing an essential role in development, homeostasis, and diseases. This paper introduces a cell tracking algorithm named HFM-Tracker (Hybrid Feature Matching Tracker) that automatically identifies cell migration behaviours in consecutive images. It combines Contour Attention (CA) and Adaptive Confusion Matrix (ACM) modules to accurately capture cell contours in each image and track the dynamic behaviors of migrating cells in the field of view. Cells are firstly located and identified via the CA module-based cell detection network, and then associated and tracked via a cell tracking algorithm employing a hybrid feature-matching strategy. This proposed HFM-Tracker exhibits superiorities in cell detection and tracking, achieving 75% in MOTA (Multiple Object Tracking Accuracy) and 65% in IDF1 (ID F1 score). It provides quantitative analysis of the cell morphology and migration features, which could further help in understanding the complicated and diverse cell migration processes.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

SGMS1 facilitates osteogenic differentiation of MSCs and strengthens osteogenesis-angiogenesis coupling by modulating Cer/PP2A/Akt pathway.

Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo. In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.

Baicalein improves the symptoms of polycystic ovary syndrome by mitigating oxidative stress and ferroptosis in the ovary and gravid placenta.

BACKGROUND: Polycystic ovary syndrome is a metabolic and hormonal disorder that is closely linked to oxidative stress. Within individuals diagnosed with PCOS, changes occur in the ovaries, resulting in an excessive buildup of iron and peroxidation of lipids, both of which may be associated with the occurrence of ferroptosis. Baicalein, a flavonoid found in the roots of Scutellaria baicalensis and widely known as Chinese skullcap, is known for its anti-inflammatory and anti-ferroptotic properties, which protect against various diseases. Nevertheless, there has been no investigation into the impact of baicalein on polycystic ovary syndrome. PURPOSE: This study aimed to correlate ferroptosis with polycystic ovary syndrome and to assess the effects of baicalein on ovarian dysfunction and placental development in pregnant patients. STUDY DESIGN AND METHODS: Polycystic ovary syndrome was induced in a rat model through the administration of dehydroepiandrosterone, and these rats were treated with baicalein. Oxidative stress and inflammation levels were assessed in serum and ovaries, and tissue samples were collected for histological and protein analyses. Furthermore, different groups of female rats were mated with male rats to observe pregnancy outcomes and tissue samples were obtained for histological, protein, and RNA sequencing. Then, RNA sequencing of the placenta was performed to determine the key genes involved in ferroptosis negative regulation (FNR) signatures. RESULTS: Baicalein was shown to reduce ovarian oxidative stress and pathology. Baicalein also ameliorated polycystic ovary syndrome by decreasing lipid peroxidation and chronic inflammation and modulating mitochondrial functions and ferroptosis in the ovaries. Specifically, glutathione peroxidase and ferritin heavy chain 1 were considerably downregulated in polycystic ovary syndrome gravid rats compared to their expression in the control group, and most of these differences were reversed after baicalein intervention. CONCLUSIONS: Our findings, initially, indicated that baicalein could potentially enhance the prognosis of individuals suffering from polycystic ovary syndrome by reducing oxidative stress and ferroptosis, thus potentially influencing the formulation of a therapeutic approach to address this condition.

Interactive boxing-cycling on frailty and activity limitations in frail and prefrail older adults: A randomized controlled trial.

BACKGROUND: Frailty is common among older adults, often associated with activity limitations during physical and walking tasks. The interactive boxing-cycling combination has the potential to be an innovative and efficient training method, and our hypothesis was that interactive boxing-cycling would be superior to stationary cycling in improving frailty and activity limitations in frail and prefrail older adults. OBJECTIVE: To examine the impact of interactive boxing-cycling on frailty and activity limitations in frail and prefrail older adults compared to stationary cycling. MATERIALS AND METHODS: A single-blinded randomized controlled trial. Forty-five participants who met at least one frailty phenotype criteria were randomly assigned to receive either interactive boxing-cycling (n = 23) or stationary-cycling (n = 22) for 36 sessions over 12 weeks. The interactive boxing-cycling was performed on a cycle boxer bike with an interactive boxing panel fixed in front of the bike. The primary outcomes were frailty status, including score and phenotypes. Secondary outcomes included activity limitations during physical and walking tasks. The pre- and post-intervention data of both groups were analyzed using a repeated measures two-way ANOVA. RESULTS: Both types of cycling significantly improved frailty scores (p<0.001). Interactive boxing-cycling was more effective than stationary cycling in reversing the frailty phenotype of muscle weakness (p = 0.03, odds ratio 9.19) and demonstrated greater improvements than stationary cycling in arm curl (p = 0.002, η2=0.20), functional reach (p = 0.001, η2=0.22), and grip strength (p = 0.02, η2=0.12) tests. Additionally, interactive boxing-cycling exhibited a greater effect on gait speed (p = 0.02, η2=0.13) and gait variability (p = 0.01, η2=0.14) during dual-task walking. CONCLUSION: In frail and prefrail older adults, interactive boxing-cycling effectively improves frailty but is not superior to stationary cycling. However, it is more effective at improving certain activity limitations. REGISTRATION NUMBER: TCTR20220328001.

CDDO regulates central and peripheral sensitization to attenuate post-herpetic neuralgia by targeting TRPV1/PKC-δ/p-Akt signals.

Postherpetic neuralgia (PHN) is a notorious neuropathic pain featuring persistent profound mechanical hyperalgesia with significant negative impact on patients' life quality. CDDO can regulate inflammatory response and programmed cell death. Its derivative also protects neurons from damages by modulating microglia activities. As a consequence of central and peripheral sensitization, applying neural blocks may benefit to minimize the risk of PHN. This study aimed to explore whether CDDO could generate analgesic action in a PHN-rats' model. The behavioural test was determined by calibrated forceps testing. The number of apoptotic neurons and degree of glial cell reaction were assessed by immunofluorescence assay. Activation of PKC-δ and the phosphorylation of Akt were measured by western blots. CDDO improved PHN by decreasing TRPV1-positive nociceptive neurons, the apoptotic neurons, and reversed glial cell reaction in adult rats. It also suppressed the enhanced PKC-δ and p-Akt signalling in the sciatic nerve, dorsal root ganglia (DRG) and spinal dorsal horn. Our research is the promising report demonstrating the analgesic and neuroprotective action of CDDO in a PHN-rat's model by regulating central and peripheral sensitization targeting TRPV1, PKC-δ and p-Akt. It also is the first study to elucidate the role of oligodendrocyte in PHN.

Emerging Data Processing Methods for Single-Entity Electrochemistry.

Single-entity electrochemistry is a powerful tool that enables the study of electrochemical processes at interfaces and provides insights into the intrinsic chemical and structural heterogeneities of individual entities. Signal processing is a critical aspect of single-entity electrochemical measurements and can be used for data recognition, classification, and interpretation. In this review, we summarize the recent five-year advances in signal processing techniques for single-entity electrochemistry and highlight their importance in obtaining high-quality data and extracting effective features from electrochemical signals, which are generally applicable in single-entity electrochemistry. Moreover, we shed light on electrochemical noise analysis to obtain single-molecule frequency fingerprint spectra that can provide rich information about the ion networks at the interface. By incorporating advanced data analysis tools and artificial intelligence algorithms, single-entity electrochemical measurements would revolutionize the field of single-entity analysis, leading to new fundamental discoveries.

Can transcranial direct current stimulation combined with interactive computerized cognitive training boost cognition and gait performance in older adults with mild cognitive impairment? a randomized controlled trial.

BACKGROUND: Older adults with Mild Cognitive Impairment (MCI) are often subject to cognitive and gait deficits. Interactive Computerized Cognitive Training (ICCT) may improve cognitive function; however, the effect of such training on gait performance is limited. Transcranial Direct Current Stimulation (tDCS) improves cognition and gait performance. It remains unclear whether combining tDCS with ICCT produces an enhanced synergistic effect on cognition and complex gait performance relative to ICCT alone. This study aimed to compare the effects of tDCS combined with ICCT on cognition and gait performance in older adults with MCI. METHOD: Twenty-one older adults with MCI were randomly assigned to groups receiving either anodal tDCS and ICCT ( tDCS + ICCT ) or sham tDCS and ICCT ( sham + ICCT ). Participants played Nintendo Switch cognitive games for 40 min per session, simultaneously receiving either anodal or sham tDCS over the left dorsolateral prefrontal cortex for the first 20 min. Cognitive and gait assessments were performed before and after 15 training sessions. RESULTS: The global cognition, executive function, and working-memory scores improved in both groups, but there were no significant interaction effects on cognitive outcomes. Additionally, the group × time interactions indicated that tDCS + ICCT significantly enhanced dual-task gait performance in terms of gait speed (p = 0.045), variability (p = 0.016), and dual-task cost (p = 0.039) compared to sham + ICCT. CONCLUSION: The combined effect of tDCS and ICCT on cognition was not superior to that of ICCT alone; however, it had a significant impact on dual-task gait performance. Administering tDCS as an adjunct to ICCT may thus provide additional benefits for older adults with MCI. TRIAL REGISTRATION: This trial was registered at http://www. CLINICALTRIALS: in.th/ (TCTR 20,220,328,009).