[Neuroimaging-based study of scalp acupuncture targets for common psychiatric diseases].

Scalp acupuncture is a unique acupuncture method, developed based on the cerebral cortex localization. Neuroimaging technology enables the combination of contemporary brain science findings with the studies of scalp stimulation sites. In this study, based on the neuroimaging literature retrieved from Neurosynth platform, the scalp stimulation targets of common psychiatric diseases are developed, which provides the stimulation target protocol of scalp acupuncture for anxiety, bipolar disorder, major depressive disorder and post-traumatic stress disorder. The paper introduces the functions of the brain areas that are involved in each target and closely related to the diseases, and lists the therapeutic methods of common acupuncture and scalp acupuncture for each disease so as to provide the references for clinical practice. These targets can be used not only for the stimulation of scalp acupuncture, but also for the different neuromodulation techniques to treat related diseases.

Estimated Prevalence of Resident-to-Resident Aggression in Assisted Living.

Importance: Resident-to-resident aggression in assisted living facilities can result in physical and psychological harm, but its prevalence is unknown. Objective: To estimate the prevalence of resident-to-resident aggression, including physical, verbal, and sexual, among residents in assisted living facilities. Design, Setting, and Participants: This study used cross-sectional, observational data from a clinical trial, in which residents of assisted living facilities were monitored for events over a 1-month period. All residents of 14 large facilities randomly selected from 2 geographic locations (N = 1067), except those receiving hospice care (n = 11), were invited to participate; 93 died or moved prior to enrollment. There were 33 family and resident refusals; 930 residents were enrolled. Data were collected between May 30, 2018, and August 11, 2022. Main Outcomes and Measures: The data are from a clinical trial testing the effectiveness of an intervention to reduce resident-to-resident aggression. In addition, the study was designed to assess prevalence using the Time 1 (baseline) data, using a probability sample of facilities to allow for this analysis. Resident-to-resident aggression was identified using a mixed-method, case-finding strategy involving 6 sources: (1) cognitively capable resident reports regarding 22 possible events, (2) direct care staff report, (3) staff member reports collected from event-reporting forms, (4) research assistant observation of events in real time, (5) facility accident or incident reports, and (6) resident records. Results: The prevalence of resident-to-resident aggression among the 930 participants (mean [SD] age, 88.0 [7.2] years; 738 women [79.4%]) during the past month was estimated to be 15.2% (141 of 930 residents; 95% CI, 12.1%-18.8%). The most common forms of aggression included verbal (11.2% [104 of 930 residents; 95% CI, 8.8%-14.2%]), physical (41 of 930 residents; 4.4% [95% CI, 3.1%-6.3%]), sexual (0.8% [7 of 930 residents; 95% CI, 0.4%-1.6%]), and other (70 of 930 residents; 7.5% [95% CI, 5.5%-10.2%]). These categories are not mutually exclusive as residents could be involved with more than 1 type of aggressive behavior. Conclusions and Relevance: In this cross-sectional, observational prevalence study, resident-to-resident aggression in assisted living facilities was highly prevalent. Verbal aggression was the most common form, and physical aggression also occurred frequently. The effects of resident-to-resident aggression can be both morbid and mortal; therefore, intervention research is needed to prevent it and to treat it when it occurs.

Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Optimization of chaotic light output in semiconductor laser systems based on multi-objective optimization algorithm.

Aiming at the weak performance of chaotic light output in semiconductor laser systems, the study designed a power control algorithm for semiconductor laser drive systems based on linear self-disturbance rejection control. Then the optimization parameters and scope were determined, and multi-objective optimization and direction preference algorithms were introduced. A chaotic optical performance optimization model based on improved multi-objective genetic algorithm was constructed using adaptive functions as evaluation indicators. These results confirmed that the larger the bandwidth of the controller, the faster the response speed of the resonant converter, but the stability was poor. When the input voltage underwent a sudden change, the current ripple coefficient of the PID algorithm was 0.55%. The linear active disturbance rejection control algorithm could ensure that the voltage and current maintained at the set values, and the output current of the algorithm was more stable when the load underwent sudden changes. The directional preference algorithm could further provide more valuable solutions on the basis of adaptive genetic algorithms. When the peak value of the autocorrelation function was equal to 0.2, the delay characteristics of chaotic light were effectively suppressed, having strong signal bandwidth and complexity. In summary, the constructed model has good application effects in optimizing chaotic optical performance and has certain positive significance for communication security.

Community Health workers United to Reduce Colorectal cancer and cardiovascular disease among people at Higher risk (CHURCH): study protocol for a randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is the second most lethal cancer in the United States (U.S.) with the highest incidence and mortality rates among African Americans (AAs) compared to other racial groups. Despite these disparities, AAs are the least likely to undergo CRC screening, have precancerous colorectal polyps removed, and have CRC detected at stages early enough for curative excision. In addition, compelling evidence links inflammatory dietary patterns to increased CRC and cardiovascular disease risk. Studies show that AA churches can successfully engage in health promotion activities including those related to cancer control. The current study seeks to leverage church-placed Community Health Workers (CHWs) to increase CRC screening and reduce CRC risk. DESIGN AND METHODS: We aim to (1) increase guideline concordant CRC screening uptake using church-placed CHWs trained in screening with a validated instrument, Brief Intervention using Motivational Interviewing, and Referral to Treatment (SBIRT); and (2) reduce dietary risk factors (inflammatory dietary patterns) linked to CRC. The latter will be addressed by culturally adapting an existing, web-based lifestyle program called Alive!. Using a Hybrid Type 1 Implementation-Effectiveness cluster randomized design, we will randomize 22 AA churches into either the dual intervention arm (CHW-led SBIRT intervention plus Alive!) or a usual care arm comprised of CRC prevention educational pamphlets and a list of CRC screening sites. We will recruit 440 subjects and evaluate the effects of both arms on screening uptake (colonoscopy, fecal DNA) (primary outcome) and dietary inflammation score (secondary outcome) at 6-month follow-up, and Life Simple7 (LS7)-a cardiovascular disease (CVD) risk score-at 6 months and 1 year (secondary outcome). Finally, guided by a racism-conscious adaptation of the Consolidated Framework for Implementation Research (CFIR), we will conduct a mixed-methods process evaluation with key stakeholders to understand multi-level influences on CRC screening and CVD risk behaviors. DISCUSSION: Church-placed CHWs are trusted influential connectors between communities and health systems. Studies have shown that these CHWs can successfully implement health prevention protocols in churches, including those related to cancer control, making them potentially important community mediators of CRC screening uptake and CRC/CVD risk reduction. TRIAL REGISTRATION: NCT05174286; clinicaltrials.gov; August 31st, 2023.

Hybrid Fabrication of Cold Metal Transfer Additive Manufacturing and Laser Metal Deposition for Ti6Al4V: The Microstructure and Dynamic/Static Mechanical Properties.

The titanium alloy components utilized in the aviation field are typically large in size and possess complex structures. By utilizing multiple additive manufacturing processes, the precision and efficiency requirements of production can be met. We investigated the hybrid additive manufacturing of Ti-6Al-4V using a combination of cold metal transfer additive manufacturing (CMTAM) and laser metal deposition (LMD), as well as the feasibility of using the CMT-LMD hybrid additive manufacturing process for fabricating Ti-6Al-4V components. Microstructural examinations, tensile testing coupled with digital image correlation and dynamic compressive experiments (by the split Hopkinson pressure bar (SHPB) system) were employed to assess the parts. The results indicate that the interface of the LMD and CMTAM zone formed a compact metallurgical bonding. In the CMTAM and LMD zone, the prior-ß grains exhibit epitaxial growth, forming columnar prior-ß grains. Due to laser remelting, the CMT-LMD hybrid additive zone experiences grain refinement, resulting in equiaxed prior-ß grains at the interface with an average grain size smaller than that of the CMTAM and LMD regions. The microstructures reveal significant differences in grain orientation and morphology among the zones, with distinct textures forming in each zone. In the CMT-LMD hybrid zone, due to interfacial strengthening, strain concentration occurs in the arc additive zone during tensile testing, leading to fracture on the CMTAM zone. Under high-strain-rate dynamic impact conditions, the LMD region exhibits ductile fracture, while the CMTAM zone demonstrates brittle fracture. The hybrid zone combines ductile and brittle fracture modes, and the CMT-LMD hybrid material exhibits superior dynamic impact performance compared to the single deposition zone.

Community Health workers United to Reduce Colorectal cancer and cardiovascular disease among people at Higher risk (CHURCH): study protocol for a randomized controlled trial.

Background: Colorectal cancer (CRC) is the second most lethal cancer in the United States (U.S.) with the highest incidence and mortality rates among African Americans (AAs) compared to other racial groups. Despite these disparities, AAs are the least likely to undergo CRC screening, have precancerous colorectal polys removed, and have CRC detected at stages early enough for curative excision. In addition, compelling evidence links inflammatory dietary patterns to increased CRC and cardiovascular disease risk. Studies show that AA churches can successfully engage in health promotion activities including those related to cancer control. The current study seeks to leverage church-placed Community Health Workers (CHWs) to increase CRC screening and reduce CRC risk. Design and Methods: We aim to (1) increase guideline concordant CRC screening uptake using church-placed CHWs trained in screening with a validated instrument, Brief Intervention using Motivational Interviewing, and Referral to Treatment (SBIRT); and (2) reduce dietary risk factors (inflammatory dietary patterns) linked to CRC. The latter will be addressed by culturally adapting an existing, web-based lifestyle program called Alive!. Using a Hybrid Type 1 Implementation-Effectiveness cluster randomized design, we will randomize 22 AA churches into either the dual intervention arm (CHW-led SBIRT intervention plus Alive!) or a usual care arm comprised of CRC prevention educational pamphlets and a list of CRC screening sites. We will recruit 440 subjects and evaluate the effects of both arms on screening uptake (colonoscopy, fecal DNA) (primary outcome) and dietary inflammation score (secondary outcome) at 6-months follow up, and Life Simple7 (LS7) - a cardiovascular disease (CVD) risk score - at 6 months and 1-year (secondary outcome). Finally, guided by a racism-conscious adaptation of the Consolidated Framework for Implementation Research (CFIR), we will conduct a mixed-methods process evaluation with key stakeholders to understand multi-level influences on CRC screening and CVD risk behaviors. Discussion: Church-placed CHWs are trusted influential connectors between communities and health systems. Studies have shown that these CHWs can successfully implement health prevention protocols in churches, including those related to cancer control, making them potentially important community mediators of CRC screening uptake and CRC/CVD risk reduction. Trial registration: NCT05174286.

Physical activity may a probably protective factor for postoperative delirium: the PNDABLE study.

Objective: This study aims to explore the relationship between physical activity (PA) and postoperative delirium (POD). Methods: We selected 400 patients from the Perioperative Neurocognitive Disorder and Biomarkers Lifestyle (PNDABLE) database, and the patients in the PNDABLE database were sampled and tested Alzheimer's biomarkers. The diagnosis of POD was made using the Confusion Assessment Scale (CAM) and the severity was assessed using Memorial Delirium Assessment Scale (MDAS). Mini-Mental State Examination (MMSE) scale was used to detect the mental state of the patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of preoperative cerebrospinal fluid (CSF) biomarkers, such as amyloid ß plaque 42 (Aß42), total tau protein (T-tau), and phosphorylated tau protein (P-tau). Logistic regression, sensitivity analysis, and post hoc analysis were used to explore the relationship between risk and protective factors on POD. We used the mediating effect to explore whether PA mediates the occurrence of POD through CSF biomarkers. Results: The incidence of POD was 17.5%. According to our research, the consequence prompted that PA might be the protective factor for POD [odds ratio (OR): 0.336, 95% confidence interval (95 CI) 0.206-0.548, P < 0.001]. The result of logistic regression revealed that CSF biomarker Aß42 (OR: 0.997, 95 CI 0.996-0.999, P < 0.001) might be a protective factor against POD, and the T-tau (OR: 1.006, 95 CI 1.003-1.009, P = 0.001) and P-tau (OR: 1.039, 95 CI 1.018-1.059, P < 0.001) might risk factors for POD. Sensitivity analysis confirmed the correlation between PA and CSF biomarkers in the patients with POD. Mediation effect analysis showed that PA may reduce the occurrence of POD partly through CSF biomarkers, such as Aß42 (proportion: 11%, P < 0.05), T-tau (proportion: 13%, P < 0.05), and P-tau (proportion: 12%, P < 0.05). Conclusion: Physical activity is probably a protective factor for POD and may exert a mediating effect through CSF biomarkers.

Single-incision plus one-port laparoscopy surgery versus conventional multi-port laparoscopy surgery for colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The efficacy of single-incision plus one-port laparoscopic surgery (SILS + 1) versus conventional laparoscopic surgery (CLS) for colorectal cancer treatment remains unclear. This study compares the short-term and long-term outcomes of SILS + 1 and CLS using a high-quality systematic review and meta-analysis. METHOD: Literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, drawing from PubMed, Embase, Web of Science, and the Cochrane Library until December 10, 2023. Statistical analysis was conducted using RevMan and Stata. RESULT: The review and meta-analysis included seven studies with 1740 colorectal cancer patients. Compared to CLS, SILS + 1 showed significant improvements in operation time (WMD = - 18.33, P < 0.00001), blood loss (WMD = - 21.31, P < 0.00001), incision length (WMD = - 2.07, P < 0.00001), time to first defecation (WMD = - 14.91, P = 0.009), time to oral intake (WMD = - 11.46, P = 0.04), and time to ambulation (WMD = - 11.52, P = 0.01). There were no significant differences in lymph node harvest, resection margins, complications, anastomotic leakage, hospital stay, disease-free survival, overall survival, and postoperative recurrence. CONCLUSIONS: Compared to CLS, SILS + 1 demonstrates superiority in shortening the surgical incision and promoting postoperative recovery. SILS + 1 can provide a safe and feasible alternative to CLS.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Development of Zn2+-controlled expression system for lactic acid bacteria and its application in engineered probiotics.

Lactococcus lactis and Streptococcus thermophilus are considered as ideal chassis of engineered probiotics, while food-grade genetic tools are limited in those strains. Here, a Zn2+-controlled gene expression (ZICE) system was identified in the genome of S. thermophilus CGMCC7.179, including a transcriptional regulator sczAst and a promoter region of cation transporter czcD (PczcDst). Specific binding of the SczAst to the palindromic sequences in PczcDst was demonstrated by EMSA analysis, suggesting the regulation role of SczAst on PczcDst. To evaluate their possibility to control gene expression in vivo, the sczAst-PczcDst was employed to drive the expression of green fluorescence protein (GFP) gene in L. lactis NZ9000 and S. thermophilus CGMCC7.179, respectively. Both of the transformants could express GFP under Zn2+ induction, while no fluorescence without Zn2+ addition. For optimal conditions, Zn2+ was used at a final concentration of 0.8 mM in L. lactis and 0.16 mM in S. thermophilus at OD600 close to 0.4, and omitting yeast extract powder in the medium unexpectedly improved GFP expression level by 2.2-fold. With the help of the ZICE system, engineered L. lactis and S. thermophilus strains were constructed to secret cytokine interleukin-10 (IL-10) with immunogenicity, and the IL-10 content in the supernatant of the engineered L. lactis was 59.37 % of that under the nisin controlled expression system. This study provided a tightly controlled expression system by the food-grade inducer Zn2+, having potential in development of engineered probiotics.

Prediction of initial objective response to drug-eluting beads transcatheter arterial chemoembolization for hepatocellular carcinoma using CT radiomics-based machine learning model.

Objective: A prognostic model utilizing CT radiomics, radiological, and clinical features was developed and validated in this study to predict an objective response to initial transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). Methods: Between January 2017 and December 2022, the baseline clinical characteristics and preoperative and postoperative follow-up imaging data of 108 HCC patients who underwent the first time treatment of DEB-TACE were analyzed retrospectively. The training group (n = 86) and the validation group (n = 22) were randomly assigned in an 8:2 ratio. By logistic regression in machine learning, radiomics, and clinical-radiological models were constructed separately. Finally, the integrated model construction involved the integration of both radiomics and clinical-radiological signatures. The study compared the integrated model with radiomics and clinical-radiological models using calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results: The objective response rate observed in a group of 108 HCC patients who received initial DEB-TACE treatment was found to be 51.9%. Among the three models, the integrated model exhibited superior predictive accuracy in both the training and validation groups. The training group resulted in an area under the curve (AUC) of 0.860, along with sensitivity and specificity values of 0.650 and 0.913, respectively. Based on the findings from the validation group, the AUC was estimated to be 0.927. Additionally, it was found that values of sensitivity and specificity were 0.875 and 0.833, respectively. In the validation group, the AUC of the integrated model showed a significant improvement when contrasted to the clinical-radiological model (p = 0.042). Nevertheless, no significant distinction was observed in the AUC when comparing the integrated model with the radiomics model (p = 0.734). The DCA suggested that the integrated model demonstrates advantageous clinical utility. Conclusion: The integrated model, which combines the CT radiomics signature and the clinical-radiological signature, exhibited higher predictive efficacy than either the radiomics or clinical-radiological models alone. This suggests that during the prediction of the objective responsiveness of HCC patients to the first DEB-TACE treatment, the integrated model yields superior outcomes.

Brain stimulation targets for chronic pain: Insights from meta-analysis, functional connectivity and literature review.

Noninvasive brain stimulation (NIBS) techniques have demonstrated their potential for chronic pain management, yet their efficacy exhibits variability across studies. Refining stimulation targets and exploring additional targets offer a possible solution to this challenge. This study aimed to identify potential brain surface targets for NIBS in treating chronic pain disorders by integrating literature review, neuroimaging meta-analysis, and functional connectivity analysis on 90 chronic low back pain patients. Our results showed that the primary motor cortex (M1) (C3/C4, 10-20 EEG system) and prefrontal cortex (F3/F4/Fz) were the most used brain stimulation targets for chronic pain treatment according to the literature review. The bilateral precentral gyrus (M1), supplementary motor area, Rolandic operculum, and temporoparietal junction, were all identified as common potential NIBS targets through both a meta-analysis sourced from Neurosynth and functional connectivity analysis. This study presents a comprehensive summary of the current literature and refines the existing NIBS targets through a combination of imaging meta-analysis and functional connectivity analysis for chronic pain conditions. The derived coordinates (with integration of the international electroencephalography (EEG) 10/20 electrode placement system) within the above brain regions may further facilitate the localization of these targets for NIBS application. Our findings may have the potential to expand NIBS target selection beyond current clinical trials and improve chronic pain treatment.

Protective effect of Bifidobacterium animalis CGMCC25262 on HaCaT keratinocytes.

Bifidobacteria are the most prevalent members of the intestinal microbiota in mammals and other animals, and they play a significant role in promoting gut health through their probiotic effects. Recently, the potential applications of Bifidobacteria have been extended to skin health. However, the beneficial mechanism of Bifidobacteria on the skin barrier remains unclear. In this study, keratinocyte HaCaT cells were used as models to evaluate the protective effects of the cell-free supernatant (CFS), heat-inactivated bacteria, and bacterial lysate of Bifidobacterium animalis CGMCC25262 on the skin barrier and inflammatory cytokines. The results showed that all the tested samples were able to upregulate the transcription levels of biomarker genes associated with the skin barrier, such as hyaluronic acid synthetase (HAS) and aquaporins (AQPs). Notably, the transcription of the hyaluronic acid synthetase gene-2 (HAS-2) is upregulated by 3~4 times, and AQP3 increased by 2.5 times when the keratinocyte HaCaT cells were co-incubated with 0.8 to 1% CFS. In particular, the expression level of Filaggrin (FLG) in HaCaT cells increased by 1.7 to 2.7 times when incubated with Bifidobacterial samples, reaching its peak at a concentration of 0.8% CFS. Moreover, B. animalis CGMCC25262 also decreased the expression of the proinflammatory cytokine RANTES to one-tenth compared to the levels observed in HaCaT cells induced with tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). These results demonstrate the potential of B. animalis CGMCC25262 in protecting the skin barrier and reducing inflammatory response.

Heme-Inducing Endothelial Pyroptosis Plays a Key Role in Radiofrequency Ablation of Hepatic Hemangioma Leading to Systemic Inflammatory Response Syndrome.

Purpose: Systemic inflammatory response syndrome (SIRS) is a common complication of radiofrequency ablation (RFA) for hepatic hemangiomas. RFA can cause hemolytic reactions during hepatic hemangioma ablation. However, the mechanisms underlying RFA-induced SIRS remain unclear. Methods: We established an orthotopic liver hemangioma model and performed radiofrequency ablation. The levels of interleukin (IL)-1ß and IL-18 and the production of ROS were measured. The wet-to-dry lung ratio, inflammation score, and in vivo endothelial cell permeability were examined. GSDMD-/- mice were used to investigate the effect of heme-inducing SIRS. RNA sequencing (RNA-seq) was performed to identify the main pathways underlying heme-induced SIRS. Western blotting and immunoprecipitation were used to determine the changes and interactions of associated proteins. Results: The levels of heme, IL-1ß, and IL-18 were significantly increased after RFA. The wet-to-dry lung ratio increased in hepatic hemangiomas after RFA, indicating that SIRS occurred. Heme induced increased levels of IL-1ß and IL-18, cell death, wet-to-dry lung radio, and inflammation score in vitro and in vivo, indicating that heme induced SIRS and pyroptosis. Furthermore, GSDMD participates in heme-induced SIRS in mice, and GSDMD deletion in mice reverses the effect of heme. Heme regulates NLRP3 activation through the NOX4/ROS/TXNIP-TRX pathway, and an N-acetyl-L-cysteine (NAC) or NOX4 inhibitor (GLX351322) reverses heme-induced SIRS. Conclusion: Our findings suggest that heme induces endothelial cell pyroptosis and SIRS in mice and decreasing heme levels and ROS scavengers may prevent SIRS in hepatic hemangioma after RFA.

Exploring 3-O-glycosylations of 20(R)-dammarane ginsenosides and the catalytic mechanism underlying the stereoselectivity with the combined assistance of AlphaFold 2 and molecular docking.

Glycosylation at C3-OH is the favorable modification for pharmaceutical activities and diversity expansion of 20(R)-dammarane ginsenosides. The 3-O-glycosylation, exclusively occurring in 20(R)-PPD ginsenosides, has never been achieved in 20(R)-PPT ginsenosides. Herein, 3-O-glycosylation of 20(R)-PPT enabled by a glycosyltransferase (GT) OsSGT2 was achieved with the combined assistance of AlphaFold 2 and molecular docking. Firstly, we combined AlphaFold2 algorithm and molecular docking to predict interactions between 20(R)-PPT and candidate GTs. A catalytically favorable binding geometry was thus identified in the OsSGT2-20(R)-PPT complex, suggesting OsSGT2 might act on 20(R)-PPT. The enzymatic assays demonstrated that OsSGT2 reacted with varied sugar donors to form 20(R)-PPT 3-O-glycosides, exhibiting donor promiscuity. Additionally, OsSGT2 displayed acceptor promiscuity, catalyzing 3-O-glucosylation of 20(R/S)-PPT, 20(R/S)-PPD and 20(R/S)-Rh1, respectively. Protein engineering on OsSGT2 was thus performed to probe its catalytic mechanism underlying its stereoselectivity. The W207A mutant preferred 20(S)-dammarane aglycons, while F395Q/A396G(QG) displayed a conversion enhancement towards both 20(R/S)-dammarane aglycons. The QG mutant was then used to synthesize 20(R)-PPT 3-O-glucoside, which displayed a moderate angiotensin-converting enzyme inhibitory effect with an IC50 of 27.5 ± 4.7 µM, superior to that of its 20(S)-epimer, with the combined assistance of target fishing and reverse docking. The water solubility of 20(R)-PPT 3-O-glucoside increased as well.

Morphological changes of the limbic system associated with acute and chronic low-back pain: A UK biobank imaging study.

BACKGROUND: Low back pain (LBP) is a major public health issue that influences physical and emotional factors integral to the limbic system. This study aims to investigate the association between LBP and brain morphometry alterations as the duration of LBP increases (acute vs. chronic). METHODS: We used the UK Biobank data to investigate the morphological features of the limbic system in acute LBP (N = 115), chronic LBP (N = 243) and controls (N = 358), and tried to replicate our findings with an independent dataset composed of 45 acute LBP participants evaluated at different timepoints throughout 1 year from the OpenPain database. RESULTS: We found that in comparison with chronic LBP and pain-free controls, acute LBP was associated with increased volumes of the nucleus accumbens, amygdala, hippocampus, and thalamus, and increased grey matter volumes in the hippocampus and posterior cingulate gyrus. In the replication cohort, we found non-significantly larger hippocampus and thalamus volumes in the 3-month visit (acute LBP) compared to the 1-year visit (chronic LBP), with similar effect sizes as the UK Biobank dataset. CONCLUSIONS: Our results suggest that acute LBP is associated with dramatic morphometric increases in the limbic system and mesolimbic pathway, which may reflect an active brain response and self-regulation in the early stage of LBP. SIGNIFICANCE: Our study suggests that LBP in the acute phase is associated with the brain morphometric changes (increase) in some limbic areas, indicating that the acute phase of LBP may represent a crucial stage of self-regulation and active response to the disease's onset.

Quantifying the Magnetic Interactions Governing Chiral Spin Textures Using Deep Neural Networks.

The interplay of magnetic interactions in chiral multilayer films gives rise to nanoscale topological spin textures that form attractive elements for next-generation computing. Quantifying these interactions requires several specialized, time-consuming, and resource-intensive experimental techniques. Imaging of ambient domain configurations presents a promising avenue for high-throughput extraction of parent magnetic interactions. Here, we present a machine learning (ML)-based approach to simultaneously determine the key magnetic interactions─symmetric exchange, chiral exchange, and anisotropy─governing the chiral domain phenomenology in multilayers, using a single binarized image of domain configurations. Our convolutional neural network model, trained and validated on over 10,000 domain images, achieved R2 > 0.85 in predicting the parameters and independently learned the physical interdependencies between magnetic parameters. When applied to microscopy data acquired across samples, our model-predicted parameter trends are consistent with those of independent experimental measurements. These results establish ML-driven techniques as valuable, high-throughput complements to conventional determination of magnetic interactions and serve to accelerate materials and device development for nanoscale electronics.

The modulation effects of the mind-body and physical exercises on the basolateral amygdala-temporal pole pathway on individuals with knee osteoarthritis.

Background/Objective: To investigate the modulatory effects of different physical exercise modalities on connectivity of amygdala subregions and its association with pain symptoms in patients with knee osteoarthritis (KOA). Methods: 140 patients with KOA were randomly allocated either to the Tai Chi, Baduanjin, Stationary cycling, or health education group and conducted a 12 week-long intervention in one of the four groups. The behavioral, magnetic resonance imaging (MRI), and blood data were collected at baseline and the end of the study. Results: Compared to the control group, all physical exercise modalities lead to significant increases in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score (pain relief) and serum Programmed Death-1 (PD-1) levels. Additionally, all physical exercise modalities resulted in decreased resting state functional connectivity (rsFC) of the basolateral amygdala (BA)-temporal pole and BA-medial prefrontal cortex (mPFC). The overlapping BA-temporal pole rsFC observed in both Tai Chi and Baduanjin groups was significantly associated with pain relief, while the BA-mPFC rsFC was significantly associated with PD-1 levels. In addition, we found increased fractional anisotropy (FA) values, a measurement of water diffusion anisotropy of tissue that responded to changes in brain microstructure, within the mind-body exercise groups' BA-temporal pole pathway. The average FA value of this pathway was positively correlated with KOOS pain score at baseline across all subjects. Conclusions: Our findings suggest that physical exercise has the potential to modulate both functional and anatomical connectivity of the amygdala subregions, indicating a possible shared pathway for various physical exercise modalities.