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Kathleen E Squires,1 Benjamin Young,2,3 Lizette Santiago,4 Robin H Dretler,5 Sharon L Walmsley,6 Henry H Zhao,7 Gary E Pakes,8 Lisa L Ross,8 Mark S Shaefer8 On behalf of the ARIES Study Team 1Thomas Jefferson University, Philadelphia, PA, 2Apex Family Medicine and Research, Denver, CO, 3International Association of Physicians in AIDS Care, Washington DC, USA; 4HOPE Clinic and Wellness Center, San Juan, Puerto Rico; 5ID Specialists of Atlanta, Decatur, GA, USA; 6University Health Network, Toronto, ON, Canada; 7GlaxoSmithKline, 8ViiV Healthcare, Research Triangle Park, NC, USA Purpose: The 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES) were stratified by gender to compare treatment responses.Methods: A total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r) whose HIV-1 RNA was

Objectives HIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy-experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long-term adverse events ( AEs). This open-label, multicentre, noninferiority study enrolled HIV-1-infected, treatment-experienced adults with confirmed HIV-1 RNA ≤ 75 HIV-1 RNA copies/mL currently receiving tenofovir/emtricitabine + atazanavir/ritonavir ( TDF/ FTC + ATV/r) for ≥ 6 months with no reported history of virological failure. Methods Participants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir ( ABC/3TC + ATV). Endpoints included the proportion of participants with HIV-1 RNA < 50 copies/mL by time to loss of virological response ( TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers. Results After 48 weeks, 76% (152 of 199) of ABC/3TC + ATV-treated and 79% (77 of 97) of TDF/ FTC + ATV/r-treated participants had HIV-1 RNA < 50 copies/mL ( TLOVR; P = 0.564). Other efficacy analyses yielded similar results. Rates of new grade 2-4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment-emergent grade 3-4 laboratory abnormalities higher with TDF/ FTC + ATV/r (36%) compared with ABC/3TC + ATV (19%). Most fasting lipid levels remained stable over time; high-density lipoprotein ( HDL) cholesterol increased modestly in ABC/3TC + ATV-treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC + ATV and were stable in participants taking TDF/ FTC + ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups. Conclusions The ABC/3TC + ATV treatment-switch group had similar viral suppression rates up to 48 weeks to the TDF/ FTC + ATV/r comparator group, with lower rates of moderate- to high-grade hyperbilirubinaemia and improvements in bone and renal biomarkers. [ABSTRACT FROM AUTHOR]

Neuroinflammation is crucial for the pathogenesis of major depression. Preclinical studies have shown the potential of anti-inflammatory agents, specifically costunolide (COS), correlate with antidepressant effects. In this study, we investigated the molecular mechanisms underlying the antidepressant actions of COS. Chronic restraint stress (CRS) was induced in male mice. The mice were treated with either intra-DG injection of COS (5 μM, 1 μL per side) or COS (20 mg/kg, i.p.) for 1 week. We showed that administration of COS through the both routes significantly ameliorated the depressive-like behavior in CRS-exposed mice. Furthermore, administration of COS significantly improved chronic stress-induced adult hippocampal neurogenesis deficits in the mice through attenuating microglia-derived neuroinflammation. We demonstrated that COS (5 μM) exerted anti-neuroinflammatory effects in LPS-treated BV2 cells via inhibiting microglial Akt/mTOR/NF-κB pathway; inactivation of mTOR/NF-κB/IL-1β pathway was required for the pro-neurogenic action of COS in CRS-exposed mice. Our results reveal the antidepressant mechanism of COS that is normalizing neuroinflammation to improve neurogenesis deficits, supporting anti-inflammatory agents as a potential therapeutic strategy for depression., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

To investigate the pollution of microplastics and heavy metals from farmland soils in the upper Han River, the pollution status and distribution characteristics of pollutants were systematically analyzed. The risk level of pollutants was evaluated using methods such as the potential ecological risk index （RI）. Source apportionment was identified using correlation analysis and cluster analysis. The results showed that ① The abundance of microplastics in farmland soils in the upper Hanjiang River ranged from 360 to 6 300 n·kg -1 , with an average abundance of 2 300.73 n·kg -1 ； the shapes were mainly films （50.00%）； and the majority of the particle sizes were less than 0.5 mm （64.31%）. Polymers of microplastics were PP, PE, PA, PET, and PS. SEM analysis revealed that the surface of microplastics was characterized as rough, porous, cracked, and torn. ② Within the ten heavy metals （V, Cr, Mn, Co, Ni, Cu, Zn, As, Cd, and Pb） that were measured, the average concentrations of heavy metals Cu, Zn, Cd, and Pb were higher than the background values by 1.28, 1.15, 1.91, and 1.34 times, respectively, while the other metals were lower than the background values, and none of the heavy metals exceeded the screening values for pollution risks in the soil environmental quality standard. ③ The study area had moderate microplastic pollution, with a risk level of Ⅱ, and low ecological risk from heavy metal pollution. The compound effect of microplastics and heavy metals needs to be assessed. ④ A significant correlation was observed between microplastics and the content of heavy metals Cr, Ni, As, Cd, and Pb in farmland soils. The sources of pollutants were agricultural-traffic sources, natural-agricultural sources, and natural-industrial sources.

Background: Well-differentiated thyroid cancer includes papillary thyroid, follicular thyroid, and Hurthle cell cancers, comprising approximately 95% of all thyroid cancers in the United States. This study aims to understand well-differentiated thyroid cancer in the Asian population., Methods: We analyzed the National Cancer Database from 2004 to 2019, categorizing the Asian population based on the available ethnicities. Multivariable logistic regression assessed the associations between ethnic groups and disease stage/nodal positivity. Survival outcomes were evaluated using the Kaplan-Meier and Cox regression analyses., Results: A total of 364,604 adult patients were analyzed. The Asian ethnic groups included were Chinese (n = 3,851), Japanese (n = 740), Filipino (n = 3,466), Korean (n = 1,567), Vietnamese (n = 1,517), Laotian (n = 101), Hmong (n = 50), Kampuchean (n = 166), Thai (n = 160), Asian Indian (n = 1,526), Pakistani (n = 167), and Pacific Islander (n = 446). Japanese, Korean, and Laotian had higher percentages of stage III disease, whereas Japanese, Filipino, and Laotian had higher proportions of stage IV disease than the White population. Most Asian ethnicities had more patients with metastasis than the White population. Korean patients exhibited a 15% increased likelihood of metastasis (odds ratio: 1.15, confidence interval: 1.03-1.28, P < .05), whereas Pakistani patients were at 40% higher odds (odds ratio: 1.40, confidence interval: 1.03-1.91, P < .05), compared with White patients. Japanese, Laotian, and Kampuchean patients experienced worse 5- and 10-year overall survival than the White population., Conclusion: Our study revealed substantial variation in well-differentiated thyroid cancer characteristics and outcomes among diverse Asian ethnicities. This challenges the notion of Asians as a homogeneous population, emphasizing tailored disease management for this heterogeneous group of patients., Competing Interests: Conflict of Interest/Disclosure The authors have indicated that they have no conflicts of interest regarding the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Parathyroidectomy has been shown to be superior to medical management in treating hypercalcemia and preserving renal allograft function in patients with tertiary hyperparathyroidism after kidney transplant. Despite this evidence, parathyroidectomy remains underused. We aimed to evaluate outcomes in patients with tertiary hyperparathyroidism after kidney transplant based on management strategy (cinacalcet or parathyroidectomy) and optimal timing of parathyroidectomy., Methods: Data from TriNetX Dataworks included adult kidney transplant patients diagnosed with tertiary hyperparathyroidism between 1998 and 2021. Patients who underwent parathyroidectomy were compared with those receiving cinacalcet. Subgroups based on parathyroidectomy timing after transplant were analyzed (within 6 months, 6 months to 1 year, and between 1 and 3 years). Descriptive statistics and relative risks were calculated using TriNetX Live., Results: Patients receiving cinacalcet (n = 162) had a 77% higher risk of persistent hypercalcemia and a 73% higher risk of elevated parathyroid hormone levels than those who underwent parathyroidectomy (n = 338) within 3-10 years after the index event (start of cinacalcet or surgery). Parathyroidectomy performed 1 year after transplant (n = 132) was associated with a 57% lower risk of kidney stone formation and patients were 2 times more likely to maintain normal glomerular filtration rate than parathyroidectomy performed 1-3 years after transplant (n = 57). Even earlier parathyroidectomy (within 6 months of kidney transplant, n = 55) showed a 62% lower risk of persistent hypercalcemia, hyperphosphatemia, and kidney stone formation than surgery between 6 months and 1 year after transplant (n = 77)., Conclusion: Parathyroidectomy is more effective than cinacalcet in managing tertiary hyperparathyroidism after kidney transplant. In addition, opting for early parathyroidectomy (within 6 months after transplant) could enhance long-term outcomes., Competing Interests: Conflict of Interest/Disclosure The authors have indicated that they have no conflicts of interest regarding the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recreational drug use has been identified as a significant risk factor for the transmission of human immunodeficiency virus (HIV). This behavior is particularly prevalent among young men who have sex with men (YMSM). However, limited research has been conducted to investigate the correlation between recreational drug use and HIV incidence within this population., Objective: To examine HIV incidence and explore the association between recreational drug use and HIV incidence among YMSM., Methods: A retrospective cohort study was conducted by a local non-governmental organization (NGO) among MSM aged 18-24 years from October 2017 to December 2023 in Tianjin, China. Participants were included if they had at least two HIV test records during this period. HIV incidence density and its 95% confidence interval (CI) were calculated using person-years (PYs) with a Poisson distribution. Risk factors for HIV incidence were identified using univariable and multivariable Cox proportional hazards regression models., Results: A total of 56 HIV seroconversions were reported with 2901.9 PYs, resulting in an overall incidence density of 1.9/100 PYs (95% CI: 1.4-2.4). Among YMSM who do not use recreational drugs (YMSM-URD), the incidence density was 1.1/100 PYs (95% CI: 0.5-1.6), while it was 2.8/100 PYs (95% CI: 1.9-3.7) among those who do use recreational drugs (YMSM-RD). Adjusted for confounders, factors associated with HIV infection included recreational drug use (adjusted hazard ratio = 2.6, 95% CI = 1.4-4.7) and unprotected anal intercourse in the past six months (adjusted hazard ratio = 2.3, 95% CI = 1.2-4.4)., Conclusions: Recreational drug use and unprotected anal intercourse significantly increase the risk of HIV infection. To effectively mitigate the spread of HIV, interventions should focus on these risk factors by employing HIV counseling and testing clinics, collaborating with NGOs focused on MSM, and establishing peer education programs aimed at YMSM., Competing Interests: Declarations Ethics approval and consent to participate The study was reviewed and approved by the Ethics Committee of the Center for AIDS Prevention of the Chinese Center for Disease Control and Prevention (No.X231018769) and written informed consent was obtained from all individuals before participation. The study was performed in accordance with the ethical guidelines of the Declaration of Helsinki (7th revision). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study explored the mechanism by which the m6A demethylase ALKBH5 mediates epithelial-mesenchymal transition (EMT) in sepsis-associated acute kidney injury (SA-AKI) and AKI-chronic kidney disease (CKD) transition. HK-2 cells were stimulated with lipopolysaccharide (LPS) to establish an in vitro model of SA-AKI. ALKBH5 expression was reduced through the transfection of si-ALKBH5. Cell viability, apoptosis, and migration were detected by CCK-8 assay, TUNEL staining, and Transwell. The levels of TNF-α, IL-1β, and IL-6 were measured by enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction or Western blotting was performed to determine the expressions of ALKBH5, miR-205-5p, DDX5, E-cadherin, and α-SMA. The m6A level was quantitatively analyzed. The expression of pri-miR-205 bound to DGCR8 and m6A-modified pri-miR-205 after intervention with ALKBH5 expression was detected by RNA immunoprecipitation. A dual-luciferase assay confirmed the binding between miR-205-5p and DDX5. ALKBH5 was highly expressed in LPS-induced HK-2 cells. Inhibition of ALKBH5 increased cell viability, repressed apoptosis, and reduced EMT. Inhibition of ALKBH5 increased the m6A modification level, thereby promoting DGCR8 binding to pri-miR-205 to increase miR-205-5p expression and eventually targeting DDX5 expression. Low expression of miR-205-5p or overexpression of DDX5 partially abolished the inhibitory effect of ALKBH5 silencing on EMT. In conclusion, ALKBH5 represses miR-205-5p expression by removing m6A modification to upregulate DDX5 expression, thereby promoting EMT and AKI-CKD transition after SA-AKI., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Intracranial aneurysm (IA) is a common cerebrovascular disease. Immune system disorders and endothelial dysfunction are essential mechanisms of its pathogenesis. This study aims to explore the therapeutic effect and mechanism of Geniposide (Gen) on IA, which has a protective impact on endothelial cells and cardiovascular and cerebrovascular diseases. IA mouse models were administered intraperitoneal injections of geniposide for 2 weeks following elastase injection into the right basal ganglia of the brain for intervention. The efficacy of Gen in treating IA was evaluated through pathological testing and transcriptome sequencing analysis of Willis ring vascular tissue. The primary mechanism of action was linked to the expression of GSK3β in Th17 cells. The percentage of splenic Th17 cell differentiation in IA mice was significantly inhibited by Gen. GSK3β/STAT3, and other pathway protein expression levels were also significantly inhibited by Gen. Additionally, TNF-α and IL-23 cytokine contents were significantly downregulated after Gen treatment. These results indicated that Gen significantly inhibited the percentage of Th17 cell differentiation, an effect that was reversed upon overexpression of the GSK3B gene. Furthermore, Gen-treated, Th17 differentiation-inducing cell-conditioned medium significantly up-regulated the expression of tight junction proteins ZO-1, Occludin, and Claudin-5 in murine aortic endothelial cells. Administering the GSK3β inhibitor Tideglusib to IA mice alleviated the severity of IA disease pathology and up-regulated aortic tight junction protein expression. In conclusion, Gen inhibits Th17 cell differentiation through GSK3β, which reduces endothelial cell injury and up-regulates tight junction protein expression., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Precision mapping of site-specific glycans using mass spectrometry is vital in glycoproteomics. However, the diversity of glycan compositions across species often exceeds database capacity, hindering the identification of rare glycans. Here, we introduce pGlycoNovo, a software within the pGlyco3 software environment, which employs a glycan first-based full-range Y-ion dynamic searching strategy. pGlycoNovo enables de novo identification of intact glycopeptides with rare glycans by considering all possible monosaccharide combinations, expanding the glycan search space to 16~1000 times compared to non-open search methods, while maintaining accuracy, sensitivity and speed. Reanalysis of SARS Covid-2 spike protein glycosylation data revealed 230 additional site-specific N-glycans and 30 previously unreported O-glycans. pGlycoNovo demonstrated high complementarity to six other tools and superior search speed. It enables characterization of site-specific N-glycosylation across five evolutionarily distant species, contributing to a dataset of 32,549 site-specific glycans on 4602 proteins, including 2409 site-specific rare glycans, and uncovering unexpected glycan fragments., (© 2024. The Author(s).)

Objectives: Recent studies have suggested that neuroinflammation may play a role in the progression of spinal muscular atrophy (SMA), and this may influence the efficacy of antisense oligonucleotide treatment. This study explored the biomarkers associated with SMA and the efficacy of nusinersen therapy., Methods: Fifteen patients with SMA were enrolled and their motor function (World Health Organization motor milestone, Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb Module [RULM] scores, and 6-minute walking test) was evaluated before, during (63 days), and after (6 months) nusinersen treatment. The concentrations of monocyte chemoactive protein 1 (MCP1), tumour necrosis factor-alpha (TNF-α), and interleukin (IL)-10 in the cerebrospinal fluid were measured at the indicated time points, and their correlations with motor function were analysed., Results: A significant increase in MCP1 was observed after 6 month's treatment compared with that before treatment, while TNF-α gradually decreased over the course of treatment. IL-10 levels were negatively correlated with HFMSE scores before treatment, and reductions in IL-10 levels were correlated with improvements in RULM scores., Conclusions: This study suggests that neuroinflammation may be associated with the severity of SMA and with the therapeutic effects of nusinersen, which could have clinical implications in the treatment of SMA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Fast and high-fidelity qubit initialization is crucial for low-frequency qubits such as fluxonium, and in applications of many quantum algorithms and quantum error correction codes. In a circuit quantum electrodynamics system, the initialization is typically achieved by transferring the state between the qubit and a short-lived cavity through microwave driving, also known as the sideband cooling process in atomic system. Constrained by the selection rules from the parity symmetry of the wave functions, the sideband transitions are only enabled by multiphoton processes which require multitone or strong driving. Leveraging the flux tunability of fluxonium, we circumvent this limitation by breaking flux symmetry to enable an interaction between a noncomputational qubit transition and the cavity excitation. With single-tone sideband driving, we realize qubit initialization with a fidelity exceeding 99% within a duration of 300 ns, robust against the variation of control parameters. Furthermore, we show that our initialization scheme has a built-in benefit in simultaneously removing the second-excited state population of the qubit, and can be easily incorporated into a large-scale fluxonium processor.

The unique 4f orbitals and abundant electronic energy levels of rare earth elements enable effective doping and modification to enhance hydrogen storage performance, making it an increasingly prominent focus of research. The structures of neutral and cationic CeH n 0/+ ( n = 2-20) clusters have been determined using the Crystal Structure AnaLYsis by Particle Swarm Optimization (CALYPSO) method in conjunction with density functional theory (DFT). Interestingly, the CeH 13 and CeH 14 + exhibit remarkable stability in the doublet state with C s and C 2v symmetry, respectively. The adsorption energy of CeH n 0/+ ( n = 2-20) suggests a preference for H atoms to chemically adsorb on Ce atoms. The analysis of molecular orbital composition reveals that the stability of both CeH 13 and CeH 14 + is attributed to the significant hybridization between the H 1s and Ce 4f orbitals. Both CeH 13 and CeH 14 + demonstrate significant hydrogen storage capacities, with values reaching 8.5 wt% and 9.1 wt%, respectively.

Stem cell-derived organoid technology is a powerful tool that revolutionizes the field of biomedical research and extends the scope of our understanding of human biology and diseases. Brain organoids especially open an opportunity for human brain research and modeling many human neurological diseases, which have lagged due to the inaccessibility of human brain samples and lack of similarity with other animal models. Brain organoids can be generated through various protocols and mimic whole brain or region-specific. To provide an overview of brain organoid technology, we summarize currently available protocols and list several factors to consider before choosing protocols. We also outline the limitations of current protocols and challenges that need to be solved in future investigation of brain development and pathobiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao and Haddad.)

Background: Despite being one of the most prevalent sleep disorders, obstructive sleep apnea hypoventilation syndrome (OSAHS) has limited information on its immunologic foundation. The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies (GWAS) and genotyping techniques using high-density genetic markers ( e.g. , SNP or CNVs). But this tactic hasn't yet been applied to OSAHS. Using a Mendelian randomization analysis, we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS., Aim: To investigate the immune cells' association with OSAHS via genetic methods, guiding future clinical research., Methods: A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS. Summary statistics for each immune cell feature were obtained from the GWAS catalog. Information on 731 immune cell properties, such as morphologic parameters, median fluorescence intensity, absolute cellular, and relative cellular, was compiled using publicly available genetic databases. The results' robustness, heterogeneity, and horizontal pleiotropy were confirmed using extensive sensitivity examination., Results: Following false discovery rate (FDR) correction, no statistically significant effect of OSAHS on immunophenotypes was observed. However, two lymphocyte subsets were found to have a significant association with the risk of OSAHS: Basophil %CD33dim HLA DR- CD66b- (OR = 1.03, 95%CI = 1.01-1.03, P < 0.001); CD38 on IgD+ CD24- B cell (OR = 1.04, 95%CI = 1.02-1.04, P = 0.019)., Conclusion: This study shows a strong link between immune cells and OSAHS through a gene approach, thus offering direction for potential future medical research., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Few studies have examined the disparities in access to care for pediatric thyroid cancers. We sought to clarify socioeconomic and patient factors that affect access to care for pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer., Methods: Using the National Cancer Database, we performed a retrospective study on pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer (2004-2019). Patients were divided into three periods (2004-2008, 2009-2013, 2014-2019) to assess for trends. The χ 2 analysis and Kruskal-Wallis test were used to test for independence of groupings for each socioeconomic and disease-related factor., Results: In all, 6,275 patients with pediatric differentiated thyroid cancer and 182 with aggressive variants of papillary thyroid cancer were analyzed. Differentiated thyroid cancer patients with Medicaid (median 18.0 miles) and those from lower-income households (median 21-30 miles) had to travel greater distances for care in recent years (2014-2019). Racial/ethnic disparities were evident; Black and Hispanic patients have higher odds of waiting >30 days for surgery (odds ratio 1.39, 1.49, P < .05, respectively) than White patients. Black patients with differentiated thyroid cancer had a higher risk of mortality compared with White and Hispanic patients (hazard ratio 4.31, 95% confidence interval: 1.95-9.51, P < .05). Nodal positivity was higher in Hispanic patients with differentiated thyroid cancer (60%, P < .05, White patients 51% and Black patients 36%). Socioeconomic factors did not significantly affect survival or nodal positivity in aggressive variants of papillary thyroid cancer., Conclusion: This study highlights disparities in access to care and survival outcomes in pediatric differentiated thyroid cancer and aggressive variants of papillary thyroid cancer. Race, income status, and type of insurance all play a role in these disparities. Understanding the complex etiologies and developing interventions to improve access and patient outcomes are crucial., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The fluxonium qubits have emerged as a promising platform for gate-based quantum information processing. However, their extraordinary protection against charge fluctuations comes at a cost: when coupled capacitively, the qubit-qubit interactions are restricted to XX interactions. Consequently, effective ZZ or XZ interactions are only constructed either by temporarily populating higher-energy states, or by exploiting perturbative effects under microwave driving. Instead, we propose and demonstrate an inductive coupling scheme, which offers a wide selection of native qubit-qubit interactions for fluxonium. In particular, we leverage a built-in, flux-controlled ZZ interaction to perform qubit entanglement. To combat the increased flux-noise-induced dephasing away from the flux-insensitive position, we use a continuous version of the dynamical decoupling scheme to perform noise filtering. Combining these, we demonstrate a 20 ns controlled-z gate with a mean fidelity of 99.53%. More than confirming the efficacy of our gate scheme, this high-fidelity result also reveals a promising but rarely explored parameter space uniquely suitable for gate operations between fluxonium qubits.

Study Design: A retrospective study., Objective: The aim of this study was to compare clinical and radiological outcomes of the anterior cervical discectomy and fusion (ACDF) with a novel zero-profile variable-angle (Zero-P VA) spacer and a traditional poly-ether-ether-ketone (PEEK) cage and plate system in cases pertaining to cervical radiculopathy/myelopathy. There are two conventional types of ACDF procedures aimed at treating symptomatic cervical spondylosis. The first one involves an uninstrumented "stand-alone" approach utilizing bone graft/cage, while the second incorporates bone graft/cage in conjunction with a front plate positioned before the vertebral bodies. Both procedures have their own inherent advantages and disadvantages. The Zero-P VA spacer, however, represents a unique synthesis by amalgamating the advantages of both traditionally typical procedures. Notably, this spacer can potentially circumvent the issue related to prevertebral soft-tissue disturbance and reduce the occurrence of dysphagia., Methods: Using our surgical database, the authors systematically conducted a retrospective analysis encompassing all patients who underwent single-level ACDF between January 2018 and January 2019, with a minimum two-year follow-up. Patients either received a Zero-P VA implant or PEEK cage coupled with plating. The Japanese Orthopedic Association (JOA) score and Visual Analogue Scale (VAS) for arm and neck pain were documented. Dysphagia was evaluated using the Eating Assessment Tool-10 (ETA-10). Additional parameters such as cervical alignment, fusion rate and the incidence of postoperative complications were assessed., Results: According to the outcomes of the statistical analysis, there was no substantial disparity that emerged in the advancements observed in the JOA and VAS metrics between the two study cohorts. Noteworthy, however, the ETA-10 scores were statistically significantly reduced in the Zero-P VA group compared to the cage and plating group (p < 0.05). At the final follow-up, there were no statistically significant differences in the height of the operated segment, Cobb angle of the fused segment, C2-C7 Cobb angle and fusion rate between the two groups (p > 0.05). However, postoperative complications were slightly lower in patients with the Zero-P VA group (7.69%) as compared to the cage and plating group (16.67%)., Conclusion: The clinical outcomes observed with the Zero-P VA spacer used for single-level ACDF were found to be satisfactory. The performance of this device is comparable or even superior to the traditional cage and plating method in preventing postoperative dysphagia and mitigating potential complications associated with the use of a plate., (© 2024. The Author(s).)

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

Buprenorphine (BUP) and methadone (MTD) are used for medication-assisted treatment (MAT) in opioid use disorder. Although both medications show improved maternal and neonatal outcomes compared with illicit opioid use during pregnancy, BUP has exhibited more favorable outcomes to newborns than MTD. The underlying cellular and molecular mechanisms for the difference between BUP and MTD are largely unknown. Here, we examined the growth and neuronal activity in human cortical organoids (hCOs) exposed to BUP or MTD. We found that the growth of hCOs was significantly restricted in the MTD-treated but not in the BUP-treated hCOs and BUP attenuated the growth-restriction effect of MTD in hCOs. Furthermore, a κ-receptor agonist restricted while an antagonist alleviated the growth-restriction effect of MTD in hCOs. Since BUP is not only a μ-agonist but a κ-antagonist, the prevention of this growth-restriction by BUP is likely due to its κ-receptor-antagonism. In addition, using multielectrode array (MEA) technique, we discovered that both BUP and MTD inhibited neuronal activity in hCOs but BUP showed suppressive effects only at higher concentrations. Furthermore, κ-receptor antagonist nBNI did not prevent the MTD-induced suppression of neuronal activity in hCOs but the NMDA-antagonism of MTD (that BUP lacks) plays a role in the inhibition of neuronal activity. We conclude that, although both MTD and BUP are μ-opioid agonists, a) the additional κ-receptor antagonism of BUP mitigates the MTD-induced growth restriction during neurodevelopment and b) the lack of NMDA antagonism of BUP (in contrast to MTD) induces much less suppressive effect on neural network communications., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Root-knot nematodes (RKNs) are highly specialized parasites that cause significant yield losses worldwide. In this study, we isolated Bacillus pumilus strain S1-10 from the rhizosphere soil of Zingiber officinale Rosc. plants and evaluated its fumigant activity against Meloidogyne incognita . S1-10 exhibited a strong repellent effect on second-stage juveniles (J2s) of M. incognita , and in vitro assays indicated that S1-10 volatile organic compounds (VOCs) suppressed J2 activity and egg hatching. Under greenhouse conditions, 71 and 79% reductions of nematodes and eggs were detected on plants treated with S-10 VOCs compared with controls. Ten VOCs were identified through gas chromatography and mass spectrometry (GC-MS), of which 2-(methylamino)-ethanol (2-ME) had strong fumigant activity against J2s of M. incognita , with an LC 50 value of 1.5 mM at 12 h. These results indicate that S1-10 represents a potential novel biocontrol agent for RKNs., Competing Interests: The author(s) declare no conflict of interest.

The high frequency, stable somatic embryo system of tea has still not been established due to the limitations of its own characteristics and therefore severely restricts the genetic research and breeding process of tea plants. In this study, the transcriptome was used to illustrate the mechanisms of gene expression regulation in the somatic embryogenesis of tea plants. The number of DEGs for the (IS intermediate stage)&#95;PS (preliminary stage), ES (embryoid stage)&#95;IS and ES&#95;PS stages were 109, 2848 and 1697, respectively. The enrichment analysis showed that carbohydrate metabolic processes were considerably enriched at the ES&#95;IS stage and performed a key role in somatic embryogenesis, while enhanced light capture in photosystem I could provide the material basis for carbohydrates. The pathway analysis showed that the enriched pathways in IS&#95;PS process were far less than those in ES&#95;IS or ES&#95;PS, and the photosynthesis and photosynthetic antenna protein pathway of DEGs in ES&#95;IS or ES&#95;PS stage were notably enriched and up-regulated. The key photosynthesis and photosynthesis antenna protein pathways and the Lhcb1 gene were discovered in tea plants somatic embryogenesis. These results were of great significance to clarify the mechanism of somatic embryogenesis and the breeding research of tea plants., (© 2023. Springer Nature Limited.)

In diabetic patients, diabetic cardiomyopathy (DCM) is one of the most common causes of death. The inflammatory response is essential in the pathogenesis of DCM. Rhein, an anthraquinone compound, is extracted from the herb rhubarb, demonstrating various biological activities. However, it is unclear whether rhein has an anti-inflammatory effect in treating DCM. In our research, we investigated the anti-inflammatory properties as well as its possible mechanism. According to the findings in vitro, rhein could to exert an anti-inflammatory effect by reducing the production of NO, TNF-α, PGE 2 , iNOS, and COX-2 in RAW264.7 cells that had been stimulated with advanced glycosylation end products (AGEs). In addition, rhein alleviated H9C2 cells inflammation injury stimulated by AGEs/macrophage conditioned medium (CM). In vivo have depicted that continuous gavage of rhein could improve cardiac function and pathological changes. Moreover, it could inhibit the accumulation of AGEs and infiltration of inflammatory factors inside the heart of rats having DCM. Mechanism study showed rhein could suppress IKKβ and IκB phosphorylation via down-regulating TRAF6 expression to inhibit NF-κB pathway in AGEs/CM-induced H9C2 cells. Moreover, the anti-inflammation effect of rhein was realized through down-regulation phosphorylation of JNK MAPK. Furthermore, we found JNK MAPK could crosstalk with NF-κB pathway by regulating IκB phosphorylation without affecting IKKβ activity. And hence, the protective mechanism of rhein may involve the inhibiting of the TRAF6-NF/κB pathway, the JNK MAPK pathway, and the crosstalk between the two pathways. These results suggested that rhein may be a promising drug candidate in anti-inflammation and inflammation-related DCM therapy., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background: The incidence of herbicide-resistant barnyardgrass is escalating in paddy fields, yet the interactions between resistant weeds and rice are largely unknown. The microbiota of herbicide-resistant barnyardgrass rhizosphere soil is critical for both barnyardgrass and rice fitness., Results: Rice has different biomass allocation and root traits in the presence of penoxsulam-resistant versus penoxsulam-susceptible barnyardgrass or in their conditioned soil. Compared to susceptible barnyardgrass, resistant barnyardgrass led to an allelopathic increase in rice root, shoot, and whole-plant biomasses. Resistant barnyardgrass recruited distinct core and unique microbes in rhizosphere soil compared to susceptible barnyardgrass. In particular, resistant barnyardgrass assembled more Proteobacteria and Ascomycota to enhance plant stress tolerance. Furthermore, the root exudates from resistant and susceptible barnyardgrass were responsible for the assembly and establishment of the root microbial structure. Importantly, (-)-loliolide and jasmonic acid in root exudates were correlated with the core microbes in the rhizosphere soil., Conclusion: The interference of barnyardgrass with rice can be mediated by rhizosphere microbial communities. Biotype-specific variation in the ability to generate soil microbial communities appears to ameliorate the negative consequences for rice growth, providing an intriguing possibility for modulation of the rhizosphere microbiota to increase crop productivity and sustainability. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Congenital systemic candidiasis is a rare disease observed in both full-term and preterm infants. It can occur with or without congenital cutaneous candidiasis (CCC) and to date, only a few cases have been reported in the literature. We report here, a case of a full-term newborn who presented with diffuse skin eruptions at birth. Blood, urine, and skin scraping cultures were positive and the aetiological agent was Candida albicans . After six weeks of anti-fungal treatment with fluconazole, the newborn was cured. Early diagnosis is crucial in preventing complications caused by candidiasis in newborns.

Despite increasing evidence of kin recognition in natural and crop plants, there is a lack of knowledge of kin recognition in herbicide-resistant weeds that are escalating in cropping systems. Here, we identified a penoxsulam-resistant barnyardgrass biotype with the ability for kin recognition from two biotypes of penoxsulam-susceptible barnyardgrass and normal barnyardgrass at different levels of relatedness. When grown with closely related penoxsulam-susceptible barnyardgrass, penoxsulam-resistant barnyardgrass reduced root growth and distribution, lowering belowground competition, and advanced flowering and increased seed production, enhancing reproductive effectiveness. However, such kin recognition responses were not occurred in the presence of distantly related normal barnyardgrass. Root segregation, soil activated carbon amendment, and root exudates incubation indicated chemically-mediated kin recognition among barnyardgrass biotypes. Interestingly, penoxsulam-resistant barnyardgrass significantly reduced a putative signaling (-)-loliolide production in the presence of closely related biotype but increased production when growing with distantly related biotype and more distantly related interspecific allelopathic rice cultivar. Importantly, genetically identical penoxsulam-resistant and -susceptible barnyardgrass biotypes synergistically interact to influence the action of allelopathic rice cultivar. Therefore, kin recognition in plants could also occur at the herbicide-resistant barnyardgrass biotype level, and intraspecific kin recognition may facilitate cooperation between genetically related biotypes to compete with interspecific rice, offering many potential implications and applications in paddy systems.

Pediatric thyroid carcinoma is on the rise. We sought to better characterize patient factors associated with this and evaluate for trends based on age groups. Additionally, we examined surgical management over time, and whether it aligns with recommendations made by the American Thyroid Association. Using the National Cancer Database (NCDB), we examined cases of thyroid cancer from 2004 to 2017, ages 1-18 years. We subdivided this cohort by age group: those <10y, 10-15y, and >15y. NCDB query yielded 5,814 cases. The annual proportion of total cases ranged from 3% to 8% for <10y, 31%-40% for 10-15y, and 52%-66% for >15y. 80-90% of cases in all age groups did indeed receive total thyroidectomy which is consistent with ATA guidelines. Our results verify an overall increase in pediatric thyroid cancer cases, occurring mostly in the 10-18 years old age range with the largest year-to-year increases in the >15y group., Competing Interests: Declaration of competing interest None of the authors have conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A quantum instruction set is where quantum hardware and software meet. We develop characterization and compilation techniques for non-Clifford gates to accurately evaluate its designs. Applying these techniques to our fluxonium processor, we show that replacing the iSWAP gate by its square root SQiSW leads to a significant performance boost at almost no cost. More precisely, on SQiSW we measure a gate fidelity of up to 99.72% and averaging at 99.31%, and realize Haar random two-qubit gates with an average fidelity of 96.38%. This is an average error reduction of 41% for the former and a 50% reduction for the latter compared to using iSWAP on the same processor.

This study constructs an evaluation index system based on demand competitiveness, basic competitiveness, industrial agglomeration, industrial competition, industrial innovation, supporting industries, and government policy competitiveness. The study selected 13 provinces with good development of the new energy vehicle (NEV) industry as the sample. Based on the competitiveness evaluation index system, an empirical analysis was conducted to evaluate the development level of the NEV industry in Jiangsu with grey relational analysis and three-way decisions. The results reveal: 1) Under the absolute level of temporal and spatial characteristic attributes, the development of Jiangsu's NEV industry is in a leading position in the country, and the competitiveness level is closer to that of Shanghai and Beijing; 2) Under the incremental level, Jiangsu's incremental level ranks in the upper and middle reaches of 13 provinces, second only to Shanghai; 3) Under the volatility level, Jiangsu's industrial development fluctuates greatly, and the level of volatility lies in the middle reaches of the country. There is a big gap with Shanghai; 4) From the perspective of overall temporal and spatial characteristics, Jiangsu's overall industrial development level is in the first echelon in China, second only to Shanghai and Beijing, indicating that Jiangsu's NEV industry has a relatively good overall development level.

Introduction: Down syndrome (DS) is a genetic disorder with an extra copy of chromosome 21 and DS remains one of the most common causes of intellectual disabilities in humans. All DS patients have Alzheimer's disease (AD)-like neuropathological changes including accumulation of plaques and tangles by their 40s, much earlier than the onset of such neuropathological changes in AD patients. Due to the lack of human samples and appropriate techniques, our understanding of DS neuropathology during brain development or before the clinical onset of the disease remains largely unexplored at the cellular and molecular levels. Methods: We used induced pluripotent stem cell (iPSC) and iPSC-derived 3D cortical organoids to model Alzheimer's disease in Down syndrome and explore the earliest cellular and molecular changes during DS fetal brain development. Results: We report that DS iPSCs have a decreased growth rate than control iPSCs due to a decreased cell proliferation. DS iPSC-derived cortical organoids have a much higher immunoreactivity of amyloid beta (Aß) antibodies and a significantly higher amount of amyloid plaques than control organoids. Although Elisa results did not detect a difference of Aß40 and Aß42 level between the two groups, the ratio of Aß42/Aß40 in the detergent-insoluble fraction of DS organoids was significantly higher than control organoids. Furthermore, an increased Tau phosphorylation (pTau S396) in DS organoids was confirmed by immunostaining and Western blot. Elisa data demonstrated that the ratio of insoluble Tau/total Tau in DS organoids was significantly higher than control organoids. Conclusion: DS iPSC-derived cortical organoids mimic AD-like pathophysiologyical phenotype in vitro , including abnormal Aß and insoluble Tau accumulation. The molecular neuropathologic signature of AD is present in DS much earlier than predicted, even in early fetal brain development, illustrating the notion that brain organoids maybe a good model to study early neurodegenerative conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao and Haddad.)

Polybrominated diphenyl ethers (PBDEs) are widespread and persistent environmental contaminants, but their association with nodular goiter (NG) remains unknown. The present case-control study of 179 NG cases and 358 matched normal controls aimed to investigate the association between PBDEs and risk of NG. The plasma concentrations of 8 PBDEs congeners (BDE-28, -47, -99, -100, -153, -154, -183, and -209) were determined by gas chromatograph-mass spectrometer. Conditional logistic regression model was used to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the association between each PBDEs congener and NG. Bayesian kernel machine regression (BKMR) was used to evaluate the association between overall levels of 8 PBDEs mixture and NG. The results of logistic model suggested that increased risk of NG was associated with elevated concentrations of all PBDEs congeners, except for BDE-209. In BKMR model, the risk of NG increased with the increase in overall exposure level of 8 PBDEs mixture. Compared to when all PBDEs mixture were at their median value, the risk of exposure-response function for NG increased by 0.34 units when all PBDEs were at their 75th percentile. In women, the results showed similar trends after additional adjustment for age at menarche and menopausal status. These findings provide novel epidemiological evidence for the prevention of NG. However, larger prospective studies are required to address the associations between PBDEs exposure and NG risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Screening and identification of active components from traditional Chinese medicines is rather challenging due to the diversity and complexity of chemical components. Herein, a comprehensive strategy based on a spectrum-effect relationship model and LC-MS analysis was developed to screen active components from Terminalia chebula fruits. The water extract of T. chebula fruits was subjected to macroporous resin column and then eluted successively with water and 30%, 50%, 70%, and 95% ethanol. The 30% ethanol eluate fractions of eighteen batches from T. chebula fruits were used for the spectrum-effect relationship study. The IC 50 values for acetylcholinesterase inhibitory and 2,2-diphenyl-1-picrylhydrazyl scavenging activities were measured, LC fingerprints were established, and 15 common peaks were specified. The spectrum-effect relationship between common peaks and IC 50 values was investigated by principal component analysis, gray relational analysis, partial least square and multiple linear regression. The 30% ethanol eluate fraction was further characterized by LC-MS analysis. The chromatographic peaks (Peaks 1, 2, 3, 5, 12, 14, 15) making great contributions to the efficacy were screened through a spectrum-effect relationship model, and sixteen components were further identified. The results suggested that the proposed strategy is simple and effective for acquiring active components from a complex matrix., (© 2022 Wiley-VCH GmbH.)

Disordered superconducting nitrides with kinetic inductance have long been considered to be leading material candidates for high-inductance quantum-circuit applications. Despite continuing efforts toward reducing material dimensions to increase the kinetic inductance and the corresponding circuit impedance, achieving further improvements without compromising material quality has become a fundamental challenge. To this end, a method to drastically increase the kinetic inductance of superconducting materials via spinodal decomposition while maintaining a low microwave loss is proposed. Epitaxial Ti 0.48 Al 0.52 N is used as a model system and the utilization of spinodal decomposition to trigger the insulator-to-superconductor transition with a drastically enhanced material disorder is demonstrated. The measured kinetic inductance increases by two to three orders of magnitude compared with the best disordered superconducting nitrides reported to date. This work paves the way for substantially enhancing and deterministically controlling the inductance for advanced superconducting quantum circuits., (© 2022 Wiley-VCH GmbH.)

Saline-alkaline stress is one of the most detrimental abiotic stresses that restrict the yield and physiological activity of maize ( Zea mays L.). In the present study, maize was planted on saline-alkali land, while 25 mg L -1 uniconazole (S3307) and 40 mg L -1 5-aminolevulinic acid (ALA) were sprayed at the stage of nine expanded leaves. Our results showed that both S3307 and ALA applications significantly increased all ear width, volume, and mass in the maturity stage. Both applications also upregulated photosynthetic efficiency via increasing the chlorophyll content, net photosynthetic rate, transpiration rate, and stomatal conductance, as well as reduced the intercellular CO 2 concentration after the silking stage. In addition, both applications upregulated further the antioxidant system via enhancing the activity of antioxidants and contents of soluble protein and sugar, as well as reducing the malondialdehyde content after the silking stage. Thus, both S3307 and ALA applications can improve maize yield in saline-alkali land via enhancing ear morphology and increasing photosynthetic efficiency and antioxidants., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2022 Xu et al.)

Superconducting qubits provide a promising path toward building large-scale quantum computers. The simple and robust transmon qubit has been the leading platform, achieving multiple milestones. However, fault-tolerant quantum computing calls for qubit operations at error rates significantly lower than those exhibited in the state of the art. Consequently, alternative superconducting qubits with better error protection have attracted increasing interest. Among them, fluxonium is a particularly promising candidate, featuring large anharmonicity and long coherence times. Here, we engineer a fluxonium-based quantum processor that integrates high qubit coherence, fast frequency tunability, and individual-qubit addressability for reset, readout, and gates. With simple and fast gate schemes, we achieve an average single-qubit gate fidelity of 99.97% and a two-qubit gate fidelity of up to 99.72%. This performance is comparable to the highest values reported in the literature of superconducting circuits. Thus our work, within the realm of superconducting qubits, reveals an alternative qubit platform that is competitive with the transmon system.

Ramie ( Boehmeria nivea ), which is rich in protein, fatty acid, vitamins and minerals, has become a potential alternative feed resource for poultry, and has attracted more and more attentions in nutrition research. The objective of this study is to evaluate the effect of dietary ramie at different concentrations on the production performance of the hens, and the quality, nutrient composition, and antioxidation of the eggs. A total of 432 34-week-old Lohmann commercial laying hens were divided into four groups, that were fed with corn-soybean meal-based control diet, control mixed with ramie at concentrations of 3, 6, or 9% separately for 8 weeks. Results showed that dietary ramie did not affect production performance. And egg yolk color gradually deepened as the inclusion levels of ramie increased. Ramie at tested concentration could significantly reduce the content of malondialdehyde (MDA) ( p = 0.002) and 3% ramie supplementation significantly increased total antioxidative capacity (T-AOC) concentrations in egg yolk compared to the control group ( p = 0.033). In addition, dietary supplementation with 6% ramie significantly reduced total cholesterol (T-CHO) content ( p < 0.05) compared with controls. For egg nutrient composition, compared with the control group, the addition of 6% ramie significantly increased ( p < 0.05) total omega-3 polyunsaturated fatty acids (n-3PUFA) and phenylalanine (Phe) in yolk. In conclusion, dietary inclusion of 6% ramie was most effective in improving the color, antioxidative capability, and reducing T-CHO contents of the egg yolks without any negative impacts on the production performance of the hens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Peng, Liu, Liao, Zhao, Duan, Wu, Liu, Wang, Liu, Li, Fan, Zhu, Qiu and Lin.)

An efficient and concise strategy has been successfully developed for merging spiro-tetrahydroquinoline with spiro-benzofuranone into a single new skeleton through asymmetric catalytic cascade reactions catalyzed by quinine-derived chiral bifunctional squaramide organocatalysts. In this approach, differently substituted spiro-tetrahydroquinoline derivatives were smoothly obtained with high yields, and excellent diastereoselectivities and enantioselectivities (up to 99% yield, up to >20 : 1 dr, up to >99% ee, 40 examples) under mild reaction conditions.

The purpose of this study was to investigate the effects of ramie (0, 3, 6, and 9%) included in diets on production performance, antioxidative capacity, serum biochemical indices, and intestinal development of laying hens. A total of 432 Lohmann commercial laying hens were randomly allotted to one of four dietary treatments and fed for 6 weeks. The results showed that the inclusion of ramie had no negative effects on laying performance, and increased (quadratic, P < 0.05) the laying rate with the highest value in the 6% ramie group. However, ramie content in the diet up to 9% reduced the apparent metabolic energy, dry matter, and organic matter apparent digestibility of laying hens compared with those in the 3% ramie group. The content of high-density lipoprotein (HDL-C) in serum was increased ( P < 0.05), but the activity of aspartate aminotransferase (AST) was decreased ( P < 0.05) by dietary ramie supplementation. As the dietary ramie level increased, the activity of serum glutathione peroxidase (GSH-Px) was increased quadratically ( P < 0.05). Compared with control, 3% ramie group significantly increased ( P < 0.01) liver total superoxide dismutase (SOD) activity. Meanwhile, the addition of 3∼6% ramie powder increased ( P < 0.05) villus height of jejunum and villus height/crypt depth (V/C) of ileum, which reflected the intestinal promotional effect of ramie powder. In conclusion, ramie in a diet of less than 9% might protect the liver and improve the antioxidative capacity with no detrimental impacts on the laying hens. Moreover, it could promote the intestinal mucosal structure and have a positive impact on the intestine health of the laying hens., Competing Interests: YL, Y-MW, G-YD, and QL was employed by Hunan Deren Husbandry Technology Co., Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Liu, Zhao, Wu, Liu, Duan, Wang, Liu, Huang, Li, Fan, Qiu, Zhu and Lin.)

With the increasing demand of new drugs for the treatment of Alzheimer's disease (AD), screening acetylcholinesterase (AChE) inhibitors from traditional Chinese medicines (TCMs) has been proved to be an effective strategy for drug discovery. In present study, a novel strategy was developed to fish out AChE inhibitors from Terminalia chebula fruits based on immobilized AChE coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular docking. For AChE immobilization, cellulose filter paper (CFP) as the carrier was modified with chitosan to be introduced to amino groups, and then AChE was modified on the amino-modified CFP through a Schiff base reaction with glutaraldehyde as a cross-linking agent. The CPF-immobilized AChE possessed advantages of a wider range for pH and temperature endurance, better storage stability, excellent reproducibility and reusability. The CPF-immobilized AChE was incubated with the extract of T. chebula fruits, and then the active components would form complexes with immobilized AChE. The complexes were further conveniently separated with inactive components by virtue of the instantaneous separation characteristic of CFP. Eventually, 25 (1-11, 13-26) potential AChE inhibitors were fished out and their structures were further identified by UPLC-QTOF-MS. Moreover, molecular docking was performed to discriminate non-specific compounds to AChE and explore binding mechanisms between potential inhibitors and AChE, and 25 compounds could be well embedded into active sites of AChE with affinities ranging from -9.9 to -6.4 kcal/mol. Inhibitory activities of screened active components on AChE were evaluated in vitro, and punicalagin, 1,3,6-tri-O-galloyl-β-D-glucose (1,3,6-TGG), chebulinic acid and geraniin exhibited excellent AChE-inhibitory properties with IC 50 values of 0.43 ± 0.03, 0.46 ± 0.02, 0.50 ± 0.03 and 0.51 ± 0.03 mM, respectively. The results indicated that the developed method was simple and efficient, and could be utilized to screen and identify potential AChE inhibitors from TCMs., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest/no competing financial interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Shao-Yang Zhao et al.)

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome featuring ectopic lipid accumulation in hepatocytes. NAFLD has been a severe threat to humans with a global prevalence of over 25% yet no approved drugs for the treatment to date. Previous studies showed that procyanidin B2 (PCB2), an active ingredient from herbal cinnamon, has an excellent hepatoprotective effect; however, the mechanism remains inconclusive. The present study aimed to investigate the protective effect and underlying mechanism of PCB2 on PA-induced cellular injury in human hepatoma HepG2 cells. Our results showed that PA-induced oxidative stress, calcium disequilibrium, and subsequent endoplasmic reticulum stress (ERS) mediated cellular injury, with elevated protein levels of GRP78, GRP94, CHOP, and hyperphosphorylation of PERK and IRE1 α as well as the increased ratio of Bax/Bcl-2, which was restored by PCB2 in a concentration-dependent manner, proving the excellent antiapoptosis effect. In addition, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, increased cell viability and decreased protein levels of GRP78 and CHOP, which is similar to PCB2, and thapsigargin (TG), the ER stress agonist, exhibited conversely meanwhile partly counteracted the hepatic protection of PCB2. What is more, upregulated protein expression of p-IKK α / β , p-NF- κ B p65, NLRP3, cleaved caspase 1, and mature IL-1 β occurred in HepG2 cells in response to PA stress while rescued with the PCB2 intervention. In conclusion, our study demonstrated that PA induces ERS in HepG2 cells and subsequently activates downstream NLRP3 inflammasome-mediated cellular injury, while PCB2 inhibits NLRP3/caspase 1/IL-1 β pathway, inflammation, and apoptosis with the presence of ERS, thereby promoting cell survival, which may provide pharmacological evidence for clinical approaches on NAFLD., Competing Interests: All authors declare no conflicts of interest., (Copyright © 2021 Yi-Ming Li et al.)

Objective: There is an increased risk of experiencing depression during perimenopause (PM), a period of rapidly changing female hormone concentrations. Women at particular risk of developing major depression (MD) during PM are those with history of mood sensitivity to female hormone fluctuations i.e., women with a history of premenstrual dysphoric disorder (PMDD) and/or post-partum depression (PPD). Depressive symptomology has been associated with fluctuations of glutamate (Glu) levels in the medial prefrontal cortex (MPFC) in MD patients as well as PMDD and PPD patients. The objective of the study was to compare MPFC Glu levels in healthy perimenopausal and reproductive-aged (RD) women. Methods: Medial prefrontal cortex Glu levels in healthy perimenopausal ( n = 15) and healthy RD women ( n = 16) were compared via Magnetic Resonance Spectroscopy (MRS) scan using a 3 Tesla (T) magnet. Absence of depressive symptomology and psychiatric comorbidity was confirmed via semi-structured interview. Participants were scanned during the early follicular phase (FP) of the menstrual cycle (MC). Results: Mean MPFC Glu concentrations were decreased in the PM group compared to RD group (PM mean = 0.57 ± 0.03, RD mean = 0.63 ± 0.06, t = -3.84, df = 23.97, p = 0.001). Conclusion: Perimenopause is associated with decreases in MPFC Glu levels. This decrease may be contributing to the increased risk of experiencing depression during PM. Further research should assess MPFC Glu levels in perimenopausal women suffering from MD., Competing Interests: KA declares receipt of two fellowship grants from Janssen Inc., Canada. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yap, Luki, Hanstock, Seres, Shandro, Hanstock, Lirette, Zhao, Aitchison and Le Melledo.)

Background: Pompe disease is a rare, progressive, and life-threatening autosomal recessive disorder. In its late-onset form, the disease is primarily characterised by mild progressive proximal limb and respiratory muscle weakness. Mutations in the acid alpha-glucosidase ( GAA ) gene cause lysosomal enzyme GAA to be significantly reduced or missing altogether, for which supplementation can be given through enzyme replacement therapy., Methods: Fourteen patients diagnosed with late-onset Pompe disease (LOPD) in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2021 were enrolled. GAA activity was measured based on enzymatic activity in dried blood spots, and next-generation sequencing was used to detect mutations in the GAA gene. The impacts of novel missense variants were determined by five different prediction algorithms. The structural figures of novel variants and their wide types were processed with PyMOL., Results: The study included 14 patients with LOPD (male-to-female ratio, 1:1) from eastern China. The median age at symptom onset and diagnosis was 15.0 years (7-36 years) and 21.5 years (8-47 years), respectively. The median diagnostic delay from onset was 3.0 years (0-22 years). Proximal muscle weakness was the first prominent symptom in 8 patients, while the other 6 patients experienced respiratory failure, chest congestion and asthma, and scoliosis. The most frequent mutation of the GAA gene was c.2238G>C (p.W746C), which was observed at an allele frequency of 14.3% (4/28) and in 28.6% of patients (4/14). Four novel variants potentially related to the pathogenicity of LOPD were found: c.1299G>C (p.Q433H), c.1409A>G (p.N470S), c.2242delG (p.E748Rfs*16), and c.2832delA (p.E945Sfs*78)., Conclusions: The c.2238G>C (p.W746C) mutation was the most common mutation in 14 patients with LOPD from eastern China. This study has identified four novel variants in patients with LOPD. Predicting the pathogenicity of these novel variants may increase the understanding of the genetic mutation spectrum in LOPD. Our findings may also improve recognition of the characteristics of Chinese patients with LOPD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-3710). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: It is unclear whether weight change after middle adulthood influences the risk of thyroid cancer. The aim of this study was to investigate associations between the risk of papillary thyroid cancer (PTC) and body mass index (BMI) and weight change after middle adulthood (age 35)., Methods: A matched case-control study based on three hospitals included 516 pairs of cases newly diagnosed with PTC and controls. Current height and weight after defecation in the morning were measured by trained nurses. During measurement, all subjects were requested to wear lightweight clothing and no shoes. Weight at age 35 was self-reported. BMI and weight change were modeled as continuous and categorical variables. Conditional and unconditional logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95%CI) for the association between BMI and weight change after middle adulthood and PTC., Results: After adjustment for covariates, measured BMI at the time of current diagnosis was positively associated with PTC (OR 1.16, 95%CI 1.10-1.21). According to WHO BMI guidelines for Asia-Pacific populations, the OR (95%CI) for PTC risk in obesity was 2.99 (1.92-4.67) compared to normal weight (p-trend <0.001). Moreover, PTC was positively associated with BMI at age 35; the OR (95%CI) for PTC risk per unit increase in BMI was 1.06 (1.02-1.11). Compared to stable weight (changed <0.5 kg/year), weight gain ≥1.0 kg/year after middle adulthood was positively associated with PTC (OR 2.57, 95%CI 1.39-4.76, p-trend <0.001). Compared to maintaining non-overweight status, the PTC risk was significantly increased in those individuals who gained weight and became overweight after middle adulthood (OR 3.82, 95%CI 2.50-5.85)., Conclusion: This study showed that high BMI and obesity were positively associated with increased risk of PTC, and weight gain after middle adulthood also could elevate the PTC risk., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Thyroid cancer (TC) has inflicted huge threats to the health of mankind. Chlorophenols (CPs) were persistent organic pollutant and can lead to adverse effects in human health, especially in thyroid. However, epidemiological studies have revealed a rare and inconsistent relationship between internal exposure to CPs and TC risk. The purpose of this study was to investigate the correlation between urinary CPs and TC risk in Chinese population. From June 2017 to September 2019, a total of 297 histologically confirmed TC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Gas chromatography-mass spectrometry (GC-MS) was used to determine the levels of three CPs in urine. Conditional logistic regression models were adopted to assess the potential association. Restricted cubic spline function was used to explore the non-liner association. After adjusting for confounding factors, multivariate analysis showed that, compared with the first quartile, the fourth quartile concentrations of 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) were associated with TC risk (odds ratio (OR) 2,4-DCP =2.28, 95% confidence interval (CI): 1.24-4.18; OR 2,4,6-TCP =3.09, 95% CI: 1.66-5.77; OR PCP =3.30, 95% CI: 1.71-6.36, respectively), when CPs were included in the multivariate model and restricted cubic spline function as continuous variables, presenting significant dose-response relationships. Meanwhile, whether in the TC group with tumor diameter > 1 cm or metastatic TC, the changes of 2,4,6 TCP and PCP concentrations were positively correlated with the risk of TC. Our study suggests that higher concentrations of urinary CPs are associated with increased TC risks. Moreover, 2,4,6-TCP and PCP have certain effects on the invasiveness of thyroid cancer. Targeted public health policies should be formulated to reduce the CP pollution. These findings need further in-depth studies to confirm and relevant mechanism also needed to be clarified., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Goiter is one of common endocrine diseases, and its etiology has not been fully elucidated. The changes in trace elements' levels have an important impact on the thyroid. We designed a case-control study, which involved 383 goiter cases and 383 matched controls. We measured these elements in the urine of participants by inductively coupled plasma optical emission spectrometry (ICP-OES), graphite furnace atomic absorption spectrometry (GFAAS) and As 3+ -Ce 4+ catalytic spectrophotometry. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select the elements into multi-element models, conditional logistic regression models were applied to analyze the association between elements and goiter risk. Bayesian kernel machine regression (BKMR) model was used to depict elements' mixtures and evaluate their joint effects. Finally, 7 elements were included in the multi-element model. We found that the concentrations of lithium (Li), strontium (Sr) and barium (Ba) had a negative effect with goiter risk, and lead (Pb) and iodine (I) showed an extreme positive effect. Additionally, compared with the lowest levels, patients with highest quartiles of I and Pb were 6.49 and 1.94 times more likely to have goiter, respectively. On the contrary, in its second and third quartiles, arsenic (As) showed a negative effect (both OR<1). BKMR model showed a certain interaction among Pb, As, Sr and Li on goiter risk. Further large sample studies are needed to confirm these findings in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We develop an algorithmic framework for contracting tensor networks and demonstrate its power by classically simulating quantum computation of sizes previously deemed out of reach. Our main contribution, index slicing, is a method that efficiently parallelizes the contraction by breaking it down into much smaller and identically structured subtasks, which can then be executed in parallel without dependencies. We benchmark our algorithm on a class of random quantum circuits, achieving greater than 10 5 times acceleration over the original estimate of the simulation cost. We then demonstrate applications of the simulation framework for aiding the development of quantum algorithms and quantum error correction. As tensor networks are widely used in computational science, our simulation framework may find further applications., (© 2021. The Author(s).)