Effects of polycyclic aromatic hydrocarbons on the gut-testis axis.

Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds which are comprised of two or more fused benzene rings. As a typical environmental pollutant, PAHs are widely distributed in water, soil, atmosphere and food. Despite extensive researches on the mechanisms of health damage caused by PAHs, especially their carcinogenic and mutagenic toxicity, there is still a lack of comprehensive summarization and synthesis regarding the mechanisms of PAHs on the gut-testis axis, which represents an intricate interplay between the gastrointestinal and reproductive systems. Thus, this review primarily focuses on the potential forms of interaction between PAHs and the gut microbiota and summarizes their adverse outcomes that may lead to gut microbiota dysbiosis, then compiles the possible mechanistic pathways on dysbiosis of the gut microbiota impairing the male reproductive function, in order to provide valuable insights for future research and guide further exploration into the intricate mechanisms underlying the impact of gut microbiota dysbiosis caused by PAHs on male reproductive function.

Sodium arsenite impairs sperm quality via downregulating the ZMYND15 and ZMYND10.

Zinc finger MYND-type containing 15 (ZMYND15) has been documented to play important roles in spermatogenesis, and mutants contribute to recessive azoospermia, severe oligozoospermia, non-obstructive azoospermia, teratozoospermia, even male infertility. ZMYND10 is involved in sperm motility. Whether environmental pollutants impair male fertility via regulating the expression of ZMYND15 and ZMYND10 has not been studied. Arsenic exposure results in poor sperm quality and male infertility. In order to investigate whether arsenic-induced male reproductive toxicity is related to the expression of ZMYND15, ZMYND10 and their target genes, we established a male rat model of sodium arsenite exposure-induced reproductive injury, measured sperm quality, serum hormone levels, mRNA and protein expressions of intratesticular ZMYND15 and ZMYND10 as well as their target genes. The results showed that, in addition to the increased mRNA expression of Tnp1, sodium arsenite exposure reduced sperm quality, serum hormone levels, and mRNA and protein expression of intratesticular ZMYND15 and ZMYND10 and their target genes in male rats compared with the control group (p < .05). Therefore, our study first showed that the environmental pollutant arsenic impairs sperm quality in male rats by reducing the expression of ZMYND10 and ZMYND15 and their regulatory genes, which provides a possible diagnostic marker for environmental pollutants-induced male infertility.

Comprehensive variant analysis of phospholipase A2 superfamily genes in large Chinese Parkinson' s disease cohorts.

To clarify the genetic role of phospholipase A2 (PLA2) genes in Parkinson's disease (PD), we performed a genetic association study in large Chinese population cohorts using next-generation sequencing. In this study, we analyzed both rare and common variants of 38 phospholipase A2 genes in two large cohorts. We detected 1558 and 1115 rare variants in these two cohorts, respectively. In both cohorts, we observed suggestive associations between specific subgroups and the risk of PD. At the single-gene level, several genes (PLA2G2D, PLA2G12A, PLA2G12B, PLA2G4F, PNPLA1, PNPLA3, PNPLA7, PLA2G7, PLA2G15, PLAAT5, and ABHD12) are suggestively associated with PD. Meanwhile, 364 and 2261 common variants were identified in two cohorts, respectively. Our study has expanded the genetic spectrum of the PLA2 family genes and suggested potential pathogenetic roles of PLA2 superfamily in PD.

Flexoelectric Engineering of Bulk Photovoltaic Photodetector.

The bulk photovoltaic effect (BPVE) offers an interesting approach to generate a steady photocurrent in a single-phase material under homogeneous illumination, and it has been extensively investigated in ferroelectrics exhibiting spontaneous polarization that breaks inversion symmetry. Flexoelectricity breaks inversion symmetry via a strain gradient in the otherwise nonpolar materials, enabling manipulation of ferroelectric order without an electric field. Combining these two effects, we demonstrate active mechanical control of BPVE in suspended 2-dimensional CuInP2S6 (CIPS) that is ferroelectric yet sensitive to electric field, which enables practical photodetection with an order of magnitude enhancement in performance. The suspended CIPS exhibits a 20-fold increase in photocurrent, which can be continuously modulated by either mechanical force or light polarization. The flexoelectrically engineered photodetection device, activated by air pressure and without any optimization, possesses a responsivity of 2.45 × 10-2 A/W and a detectivity of 1.73 × 1011 jones, which are superior to those of ferroelectric-based photodetection and comparable to those of the commercial Si photodiode.

Cost-effectiveness of medication therapy management among Medicare population and across racial/ethnic groups.

BACKGROUND: Inappropriate medication utilization among older adults is a pressing concern in the United States, owing to its high prevalence and the consequential detrimental impact it engenders. The adverse effects stemming from the inappropriate use of medication may be unequally borne by racial/ethnic minority populations, calling for greater efforts towards promoting equity in healthcare. The study objective was to assess the cost-effectiveness of Medication Therapy Management (MTM) services among Medicare beneficiaries and across racial/ethnic groups. METHODS: Medicare administrative data from 2016 to 2017 linked to Area Health Resources Files were used to analyze Medicare fee-for-service patients aged 65 or above with continuous Parts A/B/D coverage. The intervention group included new MTM enrollees in 2017; the control group referred to patients who met the general MTM eligible criteria but did not enroll in 2016 or 2017. The 2 groups were matched using a propensity score method. Effectiveness was evaluated as the proportion of appropriate medication utilization based on performance measures developed by the Pharmacy Quality Alliance. Costs were computed as total healthcare costs from Medicare perspective. A multivariable net benefit regressions with a classic linear model and Bayesian analysis were utilized. Net benefit was calculated based on willingness-to-pay thresholds at various multiples of the gross domestic product in 2017. Three-way interaction terms among dummy variables for MTM enrollment, 2017, and racial/ethnic minority groups were incorporated in a difference-in-differences study design. RESULTS: After adjusting for patient characteristics, the findings indicate that MTM receipt was associated with incremental net benefit among each race and ethnicity. For instance, the net benefit of MTM among the non-Hispanic White patients was $2498 (95% confidence interval = $1609, $3386) at a willingness-to-pay value of $59,908. The study found no significant difference in net benefits for MTM services between minority and White patients. CONCLUSION: The study provides evidence that MTM is a cost-effective tool for managing medication utilization among the Medicare population. However, MTM may not be cost-effective in reducing racial/ethnic disparities in medication utilization in the short term. Further research is needed to understand the long-term cost-effectiveness of MTM on racial/ethnic disparities.

Allergens induce upregulated IL-18 and IL-18Rα expression in blood Th2 and Th17 cells of patients with allergic asthma.

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, quantitative real-time PCR (qPCR), and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2, and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2, and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A, and IL-18 in AA patients were elevated, and they were correlated between each other. In ovalbumin (OVA)-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2, and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα-/- mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy.

Naringenin mitigates cadmium-induced cell death, oxidative stress, mitochondrial dysfunction, and inflammation in KGN cells by regulating the expression of sirtuin-1.

The objective of this study was to examine the potential protective role of naringenin against the harmful effects induced by cadmium in KGN cell line. Cell viability was evaluated by cell counting kit-8 assay. Caspase-3/-9 activities were determined by caspase-3/-9 activity assay kits, respectively. Intracellular reactive oxygen species (ROS) level was detected by ROS-Glo™ H2O2 Assay, antioxidant capacity was determined by a total antioxidant capacity assay kit. Mitochondrial membrane potential (MMP), ATP level, and ATP synthase activity were determined by JC-1, ATP assay kit, and ATP synthase activity assay kit, respectively. The mRNA expression was determined by qRT-PCR. Cadmium reduced cell viability and increased caspase-3/-9 activities in a concentration-dependent manner. Naringenin improved cell viability and reduced caspase-3/-9 activities in cadmium-stimulated KGN cells in a concentration-dependent manner. Cadmium diminished the antioxidant capacity, increased ROS production, and induced mitochondrial dysfunction in KGN cells. These effects were ameliorated by naringenin treatment in a concentration-dependent manner. Furthermore, naringenin reduced the levels of pro-inflammatory cytokines in KGN cells exposed to cadmium. SIRT1 knockdown downregulated its expression in KGN cells and compromised the protective effects of naringenin on cell viability and caspase-3/-9 activities in cadmium-stimulated KGN cells. Naringenin prevented the reduction of MMP, ATP levels, and ATP synthase activity in cadmium-stimulated KGN cells in a concentration-dependent manner. However, these protective effects were significantly reversed by SIRT1 knockdown. In conclusion, this study suggests that naringenin protects against cadmium-induced damage by regulating oxidative stress, mitochondrial function, and inflammation in KGN cells, with SIRT1 playing a potential mediating role.

[Retracted] MicroRNA­338­3p suppresses cell proliferation, migration and invasion in human malignant melanoma by targeting MACC1.

[This retracts the article DOI: 10.3892/etm.2019.7644.].

circ_0134120: a new frontier in understanding postmenopausal osteoporosis pathogenesis.

Postmenopausal osteoporosis (OP) is a prevalent skeletal disease with not fully understood molecular mechanisms. This study aims to investigate the role of circular RNA (circRNA) in postmenopausal OP and to elucidate the potential mechanisms of the circRNA-miRNA-mRNA regulatory network. We obtained circRNA and miRNA expression profiles from postmenopausal OP patients from the Gene Expression Omnibus database. By identifying differentially expressed circRNAs and miRNAs, we constructed a circRNA-miRNA-mRNA network and identified key genes associated with OP. Further, through a range of experimental approaches, including dual-luciferase reporter assays, RNA pull-down experiments, and qRT-PCR, we examined the roles of circ_0134120, miR-590-5p, and STAT3 in the progression of OP. Our findings reveal that the interaction between circ_0134120 and miR-590-5p in regulating STAT3 gene expression is a key mechanism in OP, suggesting the circRNA-miRNA-mRNA network is a potential therapeutic target for this condition.

Preparation of antibacterial hydrogel from poly(aspartic hydrazide) and quaternized N-[3-(dimethylamino) propyl] methylacrylamide copolymer with antioxidant and hemostatic effects for wound repairing.

Hydrogels as wound dressing have attracted extensive attention in past decade because they can provide moist microenvironment to promote wound healing. Herein, this research designed a multifunctional hydrogel with antibacterial property and antioxidant activity fabricated from quaternary ammonium bearing light emitting quaternized TPE-P(DAA-co-DMAPMA) (QTPDD) and poly(aspartic hydrazide) (PAH). The protocatechuic aldehyde (PCA) grafted to the hydrogel through dynamic bond endowed the hydrogel with antioxidant activity and the tranexamic acid (TXA) was loaded to enhance the hemostatic performance. The hydrogel possesses preferable gelation time for injectable application, good antioxidant property and tissue adhesion, improved hemostatic performance fit for wound repairing. Furthermore, the hydrogel has excellent antimicrobial property to both E. coli and S. aureus based on quaternary ammonium structure. The hydrogel also showed good biocompatibility and the in vivo experiments proved this hydrogel can promote the wound repairing rate. This study suggests that TXA/hydrogel with quaternary ammonium structure and dynamic grafted PCA have great potential in wound healing applications.

Integrated transcriptomic and metabolomic analyses reveals anthocyanin biosynthesis in leaf coloration of quinoa (Chenopodium quinoa Willd.).

BACKGROUND: Quinoa leaves demonstrate a diverse array of colors, offering a potential enhancement to landscape aesthetics and the development of leisure-oriented sightseeing agriculture in semi-arid regions. This study utilized integrated transcriptomic and metabolomic analyses to investigate the mechanisms underlying anthocyanin synthesis in both emerald green and pink quinoa leaves. RESULTS: Integrated transcriptomic and metabolomic analyses indicated that both flavonoid biosynthesis pathway (ko00941) and anthocyanin biosynthesis pathway (ko00942) were significantly associated with anthocyanin biosynthesis. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were analyzed between the two germplasms during different developmental periods. Ten DEGs were verified using qRT-PCR, and the results were consistent with those of the transcriptomic sequencing. The elevated expression of phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), 4-coumarate CoA ligase (4CL) and Hydroxycinnamoyltransferase (HCT), as well as the reduced expression of flavanone 3-hydroxylase (F3H) and Flavonol synthase (FLS), likely cause pink leaf formation. In addition, bHLH14, WRKY46, and TGA indirectly affected the activities of CHS and 4CL, collectively regulating the levels of cyanidin 3-O-(3'', 6''-O-dimalonyl) glucoside and naringenin. The diminished expression of PAL, 4CL, and HCT decreased the formation of cyanidin-3-O-(6"-O-malonyl-2"-O-glucuronyl) glucoside, leading to the emergence of emerald green leaves. Moreover, the lowered expression of TGA and WRKY46 indirectly regulated 4CL activity, serving as another important factor in maintaining the emerald green hue in leaves N1, N2, and N3. CONCLUSION: These findings establish a foundation for elucidating the molecular regulatory mechanisms governing anthocyanin biosynthesis in quinoa leaves, and also provide some theoretical basis for the development of leisure and sightseeing agriculture.

Effects of comprehensive medication review on opioid overuse among medicare beneficiaries.

Objectives: This study examined the effects of the comprehensive medication review of Medicare medication therapy management programs on opioid overuse among Medicare beneficiaries. Methods: This retrospective study analyzed Medicare data from 2016 to 2017. The intervention group included Medicare beneficiaries who newly received comprehensive medication review in 2017; the control group referred to patients who met the general eligible criteria for the medication therapy management program but did not enroll in 2016 or 2017. Propensity score matching was performed to increase characteristic compatibility between the intervention and control groups. Three measures of opioid overuse were analyzed: use of opioids at a high dosage, use of opioids from multiple providers, and concurrent use of opioids and benzodiazepines. The effects of comprehensive medication review on opioid overuse were analyzed with a multivariate logistic regression with an interaction term between the receipt of comprehensive medication review and the year 2017. Key Findings: The proportion of concurrent use of opioids and benzodiazepines declined at a greater rate among the recipients (2.21%) than non-recipients (1.55%) of the comprehensive medication review. In the adjusted analysis, the odds ratio of no concurrent use of opioids and benzodiazepines was 5% higher (1.05; 95% confidence interval = 1.02-1.09) among recipients than non-recipients. These significant findings were not found for the other two measures of opioid overuse. Conclusions: Comprehensive medication review is associated with reduced concurrent use of opioids and benzodiazepines among Medicare beneficiaries. Such service should be incorporated into the current approaches for addressing the opioid epidemic.

Unveiling the Synergy of Architecture and Anion Vacancy on Bi2Te3-x@NPCNFs for Fast and Stable Potassium Ion Storage.

Large volume strain and slow kinetics are the main obstacles to the application of high-specific-capacity alloy-type metal tellurides in potassium-ion storage systems. Herein, Bi2Te3-x nanocrystals with abundant Te-vacancies embedded in nitrogen-doped porous carbon nanofibers (Bi2Te3-x@NPCNFs) are proposed to address these challenges. In particular, a hierarchical porous fiber structure can be achieved by the polyvinylpyrrolidone-etching method and is conducive to increasing the Te-vacancy concentration. The unique porous structure together with defect engineering modulates the potassium storage mechanism of Bi2Te3, suppresses structural distortion, and accelerates K+ diffusion capacity. The meticulously designed Bi2Te3-x@NPCNFs electrode exhibits ultrastable cycling stability (over 3500 stable cycles at 1.0 A g-1 with a capacity degradation of only 0.01% per cycle) and outstanding rate capability (109.5 mAh g-1 at 2.0 A g-1). Furthermore, the systematic ex situ characterization confirms that the Bi2Te3-x@NPCNFs electrode undergoes an "intercalation-conversion-step alloying" mechanism for potassium storage. Kinetic analysis and density functional theory calculations reveal the excellent pseudocapacitive performance, attractive K+ adsorption, and fast K+ diffusion ability of the Bi2Te3-x@NPCNFs electrode, which is essential for fast potassium-ion storage. Impressively, the assembled Bi2Te3-x@NPCNFs//activated-carbon potassium-ion hybrid capacitors achieve considerable energy/power density (energy density up to 112 Wh kg-1 at a power density of 1000 W kg-1) and excellent cycling stability (1600 cycles at 10.0 A g-1), indicating their potential practical applications.

Integrated analysis of gut metabolome, microbiome, and brain function reveal the role of gut-brain axis in longevity.

The role of microbiota-gut-brain axis in modulating longevity remains undetermined. Here, we performed a multiomics analysis of gut metagenomics, gut metabolomics, and brain functional near-infrared spectroscopy (fNIRS) in a cohort of 164 participants, including 83 nonagenarians (NAs) and 81 non-nonagenarians (NNAs) matched with their spouses and offspring. We found that 438 metabolites were significantly different between the two groups; among them, neuroactive compounds and anti-inflammatory substances were enriched in NAs. In addition, increased levels of neuroactive metabolites in NAs were significantly associated with NA-enriched species that had three corresponding biosynthetic potentials: Enterocloster asparagiformis, Hungatella hathewayi and Oxalobacter formigenes. Further analysis showed that the altered gut microbes and metabolites were linked to the enhanced brain connectivity in NAs, including the left dorsolateral prefrontal cortex (DLPFC)-left premotor cortex (PMC), left DLPFC-right primary motor area (M1), and right inferior frontal gyrus (IFG)-right M1. Finally, we found that neuroactive metabolites, altered microbe and enhanced brain connectivity contributed to the cognitive preservation in NAs. Our findings provide a comprehensive understanding of the microbiota-gut-brain axis in a long-lived population and insights into the establishment of a microbiome and metabolite homeostasis that can benefit human longevity and cognition by enhancing functional brain connectivity.

Catalytic chemistry inspired hollow carbon nanofibers loaded with NiS/Ni as high-performance and safe Li+ reservoir.

Transition metal sulfides (TMSs) based anodes hold a very broad application prospect in lithium ion batteries (LIBs). In this work, the catalytic effect of metallic nickel at high temperature was used to generate hollow carbon nanofibers loaded with NiS and Ni (denoted as NiS/Ni@HCNF). The heteroatoms doped carbon fibers buffer the huge volumetric change of NiS during the discharge/charge process, and enhance the ion transport efficiency and electrical conductivity. In addition, the high specific surface area brought by the hollow carbon nanofibers can accelerate the electrolyte penetration and speed up the transport of ions as well as electrons. When used as anode of half cell, this electrode gives 958.5 and 612.9 mAh/g after running 1000 cycles under 1 and 2 A/g, showing the extremely-low attenuation rates of 0.0483 % per cycle and 0.0643 % per cycle, respectively. Impressively, NCM//NiS/Ni@HCNF battery shows the discharge capacity of 187.6 mAh/g at 1st cycle. Regarding the next 100 cycles, the relatively-high discharge capacities (>110 mAh/g) and coulombic efficiency (CE) values (>96 %) are discerned. It is noted that the usage of NiS/Ni@HCNF electrode improves the activation energy for thermal runaway, corroborating the elevated thermal safety of battery.

Structure of Metal-Organic Frameworks Eco-Modulated by Acid-Base Balance toward Biobased Flame Retardant in Polyurea Composites.

Biobased-functionalized metal-organic frameworks (Bio-FUN-MOFs) stand out from the crowd of candidates in the flame-retardant field due to their multipathway flame-retardant mechanisms and green synthesis processes. However, exploring and designing Bio-FUN-MOFs tend to counteract the problem of compromising the flame-retardant advantages of MOFs themselves, which inevitably results in a waste of resources. Herein, a strategy in which MOFs are ecologically regulated through acid-base balance is presented for controllable preparation of Bio-FUN-MOFs by two birds with one stone, i.e., higher flame-retardant element loading and retention of more MOF structures. Specifically, the buffer layer is created on the periphery of ZIF-67 by weak etching of biobased alkali arginine to resist the excessive etching of ZIF-67 by phytic acid when loading phosphorus source and to preserve the integrity of internal crystals as much as possible. As a proof of concept, ZIF-67 was almost completely etched out by phytic acid in the absence of arginine. The arginine and phytic acid-functionalized ZIF-67 with yolk@shell structure (ZIF@Arg-Co-PA) obtained by this strategy, as a biobased flame retardant, reduces fire hazards for polyurea composites. At only 5 wt % loading, ZIF@Arg-Co-PA imparted polyurea composites with a limiting oxygen index of 23.2%, and the peaks of heat release rate, total heat release, and total smoke production were reduced by 43.8, 32.3, and 34.3%, respectively, compared to neat polyurea. Additionally, the prepared polyurea composites have acceptable mechanical properties. This work will shed light on the advanced structural design of polymer composites with excellent fire safety, especially environmentally friendly and efficient biobased MOF flame retardants.

The genetic landscape and phenotypic spectrum of GAA-FGF14 ataxia in China: a large cohort study.

BACKGROUND: An intronic GAA repeat expansion in FGF14 was recently identified as a cause of GAA-FGF14 ataxia. We aimed to characterise the frequency and phenotypic profile of GAA-FGF14 ataxia in a large Chinese ataxia cohort. METHODS: A total of 1216 patients that included 399 typical late-onset cerebellar ataxia (LOCA), 290 early-onset cerebellar ataxia (EOCA), and 527 multiple system atrophy with predominant cerebellar ataxia (MSA-c) were enrolled. Long-range and repeat-primed PCR were performed to screen for GAA expansions in FGF14. Targeted long-read and whole-genome sequencing were performed to determine repeat size and sequence configuration. A multi-modal study including clinical assessment, MRI, and neurofilament light chain was conducted for disease assessment. FINDINGS: 17 GAA-FGF14 positive patients with a (GAA)≥250 expansion (12 patients with a GAA-pure expansion, five patients with a (GAA)≥250-[(GAA)n (GCA)m]z expansion) and two possible patients with biallelic (GAA)202/222 alleles were identified. The clinical phenotypes of the 19 positive and possible positive cases covered LOCA phenotype, EOCA phenotype and MSA-c phenotype. Five of six patients with EOCA phenotype were found to have another genetic disorder. The NfL levels of patients with EOCA and MSA-c phenotypes were significantly higher than patients with LOCA phenotype and age-matched controls (p < 0.001). NfL levels of pre-ataxic GAA-FGF14 positive individuals were lower than pre-ataxic SCA3 (p < 0.001) and similar to controls. INTERPRETATION: The frequency of GAA-FGF14 expansion in a large Chinese LOCA cohort was low (1.3%). Biallelic (GAA)202/222 alleles and co-occurrence with other acquired or hereditary diseases may contribute to phenotypic variation and different progression. FUNDING: This study was funded by the National Key R&D Program of China (2021YFA0805200 to H.J.), the National Natural Science Foundation of China (81974176 and 82171254 to H.J.; 82371272 to Z.C.; 82301628 to L.W.; 82301438 to Z.L.; 82201411 to L.H.), the Innovation Research Group Project of Natural Science Foundation of Hunan Province (2020JJ1008 to H.J.), the Key Research and Development Program of Hunan Province (2020SK2064 to H.J.), the Innovative Research and Development Program of Development and Reform Commission of Hunan Province to H.J., the Natural Science Foundation of Hunan Province (2024JJ3050 to H.J.; 2022JJ20094 and 2021JJ40974 to Z.C.; 2022JJ40783 to L.H.; 2022JJ40703 to Z.L.), the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, 2020LNJJ12 to H.J.), the Central South University Research Programme of Advanced Interdisciplinary Study (2023QYJC010 to H.J.) and the Science and Technology Innovation Program of Hunan Province (2022RC1027 to Z.C.). D.P. holds a Fellowship award from the Canadian Institutes of Health Research (CIHR).

Performance Evaluation of the uMI Panorama PET/CT System in Accordance with the National Electrical Manufacturers Association NU 2-2018 Standard.

The uMI Panorama is a novel PET/CT system using silicon photomultiplier and application-specific integrated circuit technologies and providing exceptional spatial and time-of-flight (TOF) resolutions. The objective of this study was to assess the physical performance of the uMI Panorama in accordance with the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. Methods: Spatial resolution, sensitivity, count rate performance, accuracy, image quality, and TOF resolution were evaluated in accordance with the guidelines outlined in the NEMA NU 2-2018 standard. Energy resolution was determined using the same dataset acquired for the count rate performance evaluation. Images from a Hoffman brain phantom, a mini-Derenzo phantom, and 3 patient studies were evaluated to demonstrate system performance. Results: The transaxial spatial resolution at full width at half maximum was measured as 2.88 mm with a 1-cm offset from the center axial field of view. The sensitivity at the center axial field of view was 20.1 kcps/MBq. At an activity concentration of 73.0 kBq/mL, the peak noise-equivalent count rate (NECR) reached 576 kcps with a scatter fraction of approximately 33.2%. For activity concentrations at or below the peak NECR, the maximum relative count rate error among all slices remained consistently below 3%. When assessed using the NEMA image quality phantom, overall image contrast recovery ranged from 63.2% to 88.4%, whereas background variability ranged from 4.2% to 1.1%. TOF resolution was 189 ps at 5.3 kBq/mL and was consistently lower than 200 ps for activity concentrations at or below the peak NECR. The patient studies demonstrated that scans at 2 min/bed produced images characterized by low noise and high contrast. Clear delineation of nuclei, spinal cords, and other substructures of the brain was observed in the brain PET images. Conclusion: uMI Panorama, the world's first commercial PET system with sub-200-ps TOF resolution, demonstrated fine spatial and fast TOF resolutions, robust count rate performance, and high quantification accuracy across a wide range of activity levels. This advanced technology offers enhanced diagnostic capability for detecting small and low-contrast lesions while showing promising potential under high-count-rate imaging scenarios.

Effects of Medicare Part D medication therapy management on racial/ethnic disparities in adherence to antidementia medications among patients with Alzheimer's disease and related dementias: An observational study.

Background: Evidence is sparse on the effects of Medicare medication therapy management (MTM) on racial/ethnic disparities in medication adherence among patients with Alzheimer's disease and related dementias. Objectives: This study examined the Medicare MTM program's effects on racial/ethnic disparities in the adherence to antidementia medications among patients with Alzheimer's disease and related dementias. Methods: This is a retrospective analysis of 100% of 2010-2017 Medicare Parts A, B, and D data linked to Area Health Resources Files. The study outcome was nonadherence to antidementia medications, and intervention was defined as new MTM enrollment in 2017. Propensity score matching was conducted to create intervention and comparison groups with comparable characteristics. A difference-in-differences model was employed with logistic regression, including interaction terms of dummy variables for the intervention group and racial/ethnic minorities. Results: Unadjusted comparisons revealed that Black, Hispanic, and Asian/Pacific Islander patients were more likely to be nonadherent than non-Hispanic White (White) patients in 2016. Differences in odds of nonadherence between Black and White patients among the intervention group were lower in 2017 than in 2016 by 27% (odds ratios [OR]: 0.73, 95% confidence interval [CI]: 0.65-0.82). A similar lowering was seen between Hispanic and White patients by 26% (OR: 0.74, 95% CI: 0.63-0.87). MTM enrollment was associated with reduced disparities in nonadherence for Black-White patients of 33% (OR: 0.67, 95% CI: 0.57-0.78) and Hispanic-White patients of 19% (OR: 0.81, 95% CI: 0.67-0.99). Discussion: The Medicare MTM program was associated with lower disparities in adherence to antidementia medications between Black and White patients, and between Hispanic and White patients in the population with Alzheimer's disease and related dementias. Conclusions: Expanding the MTM program may particularly benefit racial/ethnic minorities in Alzheimer's disease and related dementia care.

Local and Remote Chemogenetic Suppression of Hippocampal Seizures in Rats.

BACKGROUND: Innovative treatments of refractory epilepsy are widely desired, for which chemogenetic technology can provide region- and cell-type-specific modulation with relative noninvasiveness. OBJECTIVES: We aimed to explore the specific applications of chemogenetics for locally and remotely networks controlling hippocampal seizures. METHODS: A virus coding for a modified human Gi-coupled M4 muscarinic receptor (hM4Di) on pyramidal cells was injected into either the right hippocampal CA3 or the bilateral anterior nucleus of the thalamus (ANT) in rats. After one month, seizures were induced by 4-aminopyridine (4-AP) injection into the right CA3. Simultaneously, clozapine-N-oxide (CNO) (2.5 mg/kg) or clozapine (0.1 mg/kg), the specific ligands acting on hM4Di, were injected intraperitoneally. We also set up hM4Di control and clozapine control groups to eliminate the influence of viral transfection and the ligand alone on the experimental results. RESULTS: For both local and remote controls, the mean seizure duration was significantly reduced upon ligand application in the experimental groups. Seizure frequency, on the other hand, only showed a significant decrease in local control, with a lower frequency in the clozapine group than in the CNO group. Both the effects of CNO and clozapine were time-dependent, and clozapine was faster than CNO in local seizure control. CONCLUSION: This study shows the potency of chemogenetics to attenuate hippocampal seizures locally or remotely by activating the transfected hM4Di receptor with CNO or clozapine. ANT is suggested as a potentially safe chemogenetic application target in the epileptic network for focal hippocampal seizures.