Measuring Greenspace in Rural Areas for Studies of Birth Outcomes: A Comparison of Street View Data and Satellite Data.

Using street view data, in replace of remotely sensed (RS) data, to study the health impact of greenspace has become popular. However, direct comparisons of these two methods of measuring greenspace are still limited, and their findings are inconsistent. On the other hand, almost all studies of greenspace focus on urban areas. The effectiveness of greenspace in rural areas remains to be investigated. In this study, we compared measures of greenspace based on the Google Street View data with those based on RS data by calculating the correlation between the two and evaluating their associations with birth outcomes. Besides the direct measures of greenness, we also compared the measures of environmental diversity, calculated with the two types of data. Our study area consists of the States of New Hampshire and Vermont, USA, which are largely rural. Our results show that the correlations between the two types of greenness measures were weak to moderate, and the greenness at an eye-level view largely reflects the immediate surroundings. Neither the street view data- nor the RS data-based measures identify the influence of greenspace on birth outcomes in our rural study area. Interestingly, the environmental diversity was largely negatively associated with birth outcomes, particularly gestational age. Our study revealed that in rural areas, the effectiveness of greenspace and environmental diversity may be considerably different from that in urban areas.

DJ-1 protects cell death from a mitochondrial oxidative stress due to GBA1 deficiency.

BACKGROUND: GBA1 mutations are the most common genetic risk factor for development of Parkinson's disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. OBJECTIVE: In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. METHODS: GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. RESULTS: We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. CONCLUSION: Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations.

The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents.

Novel psychoactive substances (NPSs) are new psychotropic drugs designed to evade substance regulatory policies. 25E-NBOMe (2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) has recently been identified as an NPS, and its recreational misuse has been reported to be rapidly increasing. However, the psychopharmacological effects and mechanisms of 25E-NBOMe have not been studied. We examined the abuse potential of 25E-NBOMe using the conditioned place preference in male mice and self-administration paradigms in male rats. Additionally, immunoblot assay, enzyme-linked immunosorbent assay, and microdialysis were used to determine the molecular effects of 25E-NBOMe in the nucleus accumbens (NAc). Our data demonstrated that 25E-NBOMe induces conditioned place preference, and the dopaminergic signaling in the NAc mediates these. Following 25E-NBOMe administration, expression of dopamine transporter and dopamine D1 receptor (D1DR) were enhanced in the NAc of male mice, and NAc dopamine levels were reduced in both male mice and rats. Induction of intracellular dopaminergic pathways, DARPP32, and phosphorylation of CREB in the NAc of male mice was also observed. Significantly, pharmacological blockade of D1DR or chemogenetic inhibition of D1DR-expressing medium spiny neurons in the NAc attenuated 25E-NBOMe-induced conditioned place preference in male mice. We also examined the hallucinogenic properties of 25E-NBOMe using the head twitch response test in male mice and found that this behavior was mediated by serotonin 2A receptor activity. Our findings demonstrate that D1DR signaling may govern the addictive potential of 25E-NBOMe. Moreover, our study provides new insights into the potential mechanisms of substance use disorder and the improvement of controlled substance management.

Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis.

BACKGROUND: The systemic inflammatory response index (SIRI) has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms. However, research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer surgery. AIM: To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients, who received robotic radical gastric cancer surgery. METHODS: Initially, an exhaustive retrieval was performed in the PubMed, the Cochrane Library, EMBASE, Web of Science, and Scopus databases to identify relevant studies. Subsequently, a meta-analysis was executed on 6 cohort studies identifying the value of the SIRI in assessing the survival of gastric cancer patients. Additionally, the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators. The association between preoperative SIRI levels and 5-year overall survival (OS) and disease-free survival (DFS) was assessed. RESULTS: The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer. Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer. SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities, T-stage, carcinoembryonic antigen levels, the development of early serious postoperative complications, and the rate of lymph node metastasis. CONCLUSION: SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

The relationship between brain metastasis and HER2 expression status in gastric cancer

Background Brain metastasis (BM) in gastric cancer (GC) is underestimated, and human epidermal growth factor receptor 2 (HER2) overexpression is a durable poor prognostic factor. We explored the relationship between the two and made a survival analysis. Methods HER2 expression and BM status were collected from GC patients who were diagnosed between December 2009 and May 2021. We collected GC patients diagnosed between 2010 and 2016 from the SEER database. The primary endpoint was survival from the diagnosis of BM. Multivariable logistic regression was used to determine potential risk factors of BM at diagnosis in SEER database. Survival analysis was performed using the Kaplan–Meier method. Result There were 513 HER2-positive GC patients, including 16 (3.1%) with BM. Among 38 brain metastasis GC patients we collected, 16 (42.1%) patients were HER2 positive. We collected 34,199 GC patients from the SEER database and there were 260 (0.76%) patients with BM at diagnosis. GC patients that are male, white, of younger age, with primary lesions located in the proximal stomach or with distant lymph nodes, liver, bone, or lung metastasis are more likely to develop BM. The median overall survival time from diagnosis of BM was 12.73 months, and the survival time from brain metastasis of HER2-positive patients was numerically shorter, though the difference was not significant (5.30 months vs.16.13 months, P = 0.28.) Conclusion The incidence of BM in patients with HER2-positive gastric cancer is 4.08 times higher than that in general patients. The median overall survival time from BM is shorter for HER2-positive patients (AU)

Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second­line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study.

Anti-programmed cell death 1 immuno-monotherapy has become the second-line standard treatment for advanced esophageal squamous cell carcinoma (ESCC) after the failure of first-line chemotherapy. However, new biomarkers are still needed to identify patients at risk of tumor progression and to select patients with advanced ESCC who are likely to benefit from immunotherapy. A total of 12 patients with advanced ESCC treated with tislelizumab were prospectively enrolled and endoscopic biopsy samples were collected. Plasma was obtained prior to and after every 2-3 treatment cycles with tislelizumab and when disease progression occurred. Targeted sequencing of 425 genes from plasma cell-free DNA, DNA from leukocytes and fixed esophageal tumor biopsies was performed. The patients underwent imaging analyses every 6-8 weeks until disease progression. The association between status of circulating tumor DNA (ctDNA) or changes in ctDNA following tislelizumab immunotherapy and response, tumor progression and survival was determined. All patients had evaluable next-generation sequencing results at the time of analysis. The results showed that patients with ESCC with liver metastasis had a significantly shorter median progression-free survival (mPFS: 1.4 vs. 11.7 months; P=0.037). TSC complex subunit 2 [11.7 months vs. not reached (NR); P=0.004] and zinc finger protein 217 (11.7 months vs. NR; P=0.022) gene mutations were the independent and negative prognostic factors for median overall survival (OS), respectively. Of note, ctDNA dynamic changes expressed as ∆ mutant molecules per milliliter of plasma (∆MMPM; MMPM detected at the first monitoring time-point after the first infusion of tislelizumab as baseline MMPM) predicted progression-free survival (PFS) and OS more accurately compared to the ctDNA change of an individual gene. ∆MMPM <20% was an independent predictor of PFS (2.8 vs. 14.6 months; P=0.029), although there was no significant difference for OS (16.7 vs. 17.6 months; P=0.830). In conclusion, changes in ctDNA levels were associated with anti-tumor effects, progression and disease-specific survival. ctDNA sequencing is promising for predicting response and progression after tislelizumab immunotherapy as second-line monotherapy for advanced ESCC [the present study was part of the RATIONALE-302 study (ClinicalTrials.gov identifier no. NCT03430843; 29.01.2018)].

Micromechanism for Copper-Deficiency Enhanced Stability: A Quasi In Situ TEM Study of Electric-Induced Structural Evolution in Cu2-x(S, Se) Liquid-Like Thermoelectric Materials.

Cu-based liquid-like thermoelectric materials have garnered tremendous attention due to their inherent ultralow lattice thermal conductivity. However, their practical application is hampered by stability issues under a large current or temperature gradient. It has been reported that introduction of copper vacancies can enhance the chemical stability, whereas the micromechanism behind this macroscopic improvement still remains unknown. Here, we have established a quasi in situ TEM method to examine and compare the structural evolution of Cu2-xS0.2Se0.8 (x = 0, 0.05) under external electric fields. It is then found that the preset Cu vacancies could favor the electric-induced formation of a more stable intermediate phase, i.e., the hexagonal CuSe-type structure in the form of either lamellar defects (majorly) or long-range order (minorly), in which ordering of S and Se also occurred. Thereby, copper and chalcogen atoms could largely be solidified into the matrix, and the elemental deposition and evaporation process is mitigated under an electric field.

High-Throughput Strategies in the Discovery of Thermoelectric Materials.

Searching for new high-performance thermoelectric (TE) materials that are economical and environmentally friendly is an urgent task for TE society, but the advancements are greatly limited by the time-consuming and high cost of the traditional trial-and-error method. The significant progress achieved in the computing hardware, efficient computing methods, advance artificial intelligence algorithms, and rapidly growing material data have brought a paradigm shift in the investigation of TE materials. Many electrical and thermal performance descriptors are proposed and efficient high-throughput (HTP) calculation methods are developed with the purpose to quickly screen new potential TE materials from the material databases. Some HTP experiment methods are also developed which can increase the density of information obtained in a single experiment with less time and lower cost. In addition, machine learning (ML) methods are also introduced in thermoelectrics. In this review, the HTP strategies in the discovery of TE materials are systematically summarized. The applications of performance descriptor, HTP calculation, HTP experiment, and ML in the discovery of new TE materials are reviewed. In addition, the challenges and possible directions in future research are also discussed.

Modeling critical thermoelectric transports driven by band broadening and phonon softening.

Critical phenomena are one of the most captivating areas of modern physics, whereas the relevant experimental and theoretical studies are still very challenging. Particularly, the underlying mechanism behind the anomalous thermoelectric properties during critical phase transitions remains elusive, i.e., the current theoretical models for critical electrical transports are either qualitative or solely focused on a specific transport parameter. Herein, we develop a quantitative theory to model the electrical transports during critical phase transitions by incorporating both the band broadening effect and carrier-soft TO phonon interactions. It is found that the band-broadening effect contributes an additional term to Seebeck coefficient, while the carrier-soft TO phonon interactions greatly affects both electrical resistivity and Seebeck coefficient. The universality and validity of our model are well confirmed by experimental data. Furthermore, the features of critical phase transitions are effectively tuned. For example, alloying S in Cu2Se can reduce the phase transition temperature but increase the phase transition parameter b. The maximum thermoelectric figure of merit zT is pushed to a high value of 1.3 at the critical point (377 K), which is at least twice as large as those of normal static phases. This work not only provides a clear picture of the critical electrical transports but also presents new guidelines for future studies in this exciting area.

Greenspace and Land Cover Diversity During Pregnancy in a Rural Region, and Associations With Birth Outcomes.

Beneficial effects on health outcomes have been observed from exposure to spaces with substantial green vegetation ("greenspace"). This includes studies of greenspace exposure on birth outcomes; however, these have been conducted largely in urban regions. We characterized residential exposure to greenspace and land cover diversity during pregnancy in rural northern New England, USA, investigating whether variation in greenspace or diversity related to newborn outcomes. Five landscape variables (greenspace land cover, land cover diversity, impervious surface area, tree canopy cover, and the Normalized Difference Vegetation Index) were aggregated within six circular zones of radii from 100 to 3,000 m around residential addresses, and distance to conservation land was measured, providing a total of 31 greenspace and diversity metrics. Four birth outcomes along with potentially confounding variables were obtained from 1,440 participants in the New Hampshire Birth Cohort Study. Higher greenspace land cover up to 3,000 m was associated with larger newborn head circumference, while impervious surface area (non-greenspace) had the opposite association. Further, birth length was positively associated with land cover diversity. These findings support beneficial health impacts of greenspace exposure observed in urban regions for certain health outcomes, such as newborn head circumference and length but not others such as birthweight and gestational age. Further our results indicate that larger radius buffer zones may be needed to characterize the rural landscape. Vegetation indices may not be interchangeable with other greenspace metrics such as land cover and impervious surface area in rural landscapes.

Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes.

Mitochondrial toxicity induced by therapeutic drugs is a major contributor for cardiotoxicity, posing a serious threat to pharmaceutical industries and patients' lives. However, mitochondrial toxicity testing is not incorporated into routine cardiac safety screening procedures. To accurately model native human cardiomyocytes, we comprehensively evaluated mitochondrial responses of adult human primary cardiomyocytes (hPCMs) to a nucleoside analog, remdesivir (RDV). Comparison of their response to human pluripotent stem cell-derived cardiomyocytes revealed that the latter utilized a mitophagy-based mitochondrial recovery response that was absent in hPCMs. Accordingly, action potential duration was elongated in hPCMs, reflecting clinical incidences of RDV-induced QT prolongation. In a screen for mitochondrial protectants, we identified mitochondrial ROS as a primary mediator of RDV-induced cardiotoxicity. Our study demonstrates the utility of hPCMs in the detection of clinically relevant cardiac toxicities, and offers a framework for hPCM-based high-throughput screening of cardioprotective agents.

The relationship between brain metastasis and HER2 expression status in gastric cancer.

BACKGROUND: Brain metastasis (BM) in gastric cancer (GC) is underestimated, and human epidermal growth factor receptor 2 (HER2) overexpression is a durable poor prognostic factor. We explored the relationship between the two and made a survival analysis. METHODS: HER2 expression and BM status were collected from GC patients who were diagnosed between December 2009 and May 2021. We collected GC patients diagnosed between 2010 and 2016 from the SEER database. The primary endpoint was survival from the diagnosis of BM. Multivariable logistic regression was used to determine potential risk factors of BM at diagnosis in SEER database. Survival analysis was performed using the Kaplan-Meier method. RESULT: There were 513 HER2-positive GC patients, including 16 (3.1%) with BM. Among 38 brain metastasis GC patients we collected, 16 (42.1%) patients were HER2 positive. We collected 34,199 GC patients from the SEER database and there were 260 (0.76%) patients with BM at diagnosis. GC patients that are male, white, of younger age, with primary lesions located in the proximal stomach or with distant lymph nodes, liver, bone, or lung metastasis are more likely to develop BM. The median overall survival time from diagnosis of BM was 12.73 months, and the survival time from brain metastasis of HER2-positive patients was numerically shorter, though the difference was not significant (5.30 months vs.16.13 months, P = 0.28.) CONCLUSION: The incidence of BM in patients with HER2-positive gastric cancer is 4.08 times higher than that in general patients. The median overall survival time from BM is shorter for HER2-positive patients.

High Thermoelectric Power Factors in Plastic/Ductile Bulk SnSe2 -Based Crystals.

The recently discovered plastic/ductile inorganic thermoelectric (TE) materials open a new avenue for the fabrication of high-efficiently flexible TE devices, which can utilize the small temperature difference between human body and environment to generate electricity. However, the maximum power factor (PF) of current plastic/ductile TE materials is usually around or less than 10 µW cm-1 K-2 , much lower than the classic brittle TE materials. In this work, a record-high PF of 18.0 µW cm-1 K-2 at 375 K in plastic/ductile bulk SnSe2 -based crystals is reported, superior to all the plastic inorganic TE materials and flexible organic TE materials reported before. The origin of such high PF is from the modulation of material's stacking forms and polymorph crystal structures via simultaneously doping Cl/Br at Se-site and intercalating Cu inside the van der Waals gap, leading to the significantly enhanced carrier concentrations and mobilities. An in-plane fully flexible TE device made of the plastic/ductile SnSe2 -based crystals is successfully developed to show a record-high normalized maximum power density to 0.18 W m-1 under a temperature difference of 30 K. This work indicates that the plastic/ductile material can realize high TE power factor to achieve large output electric power density in flexible TE technology.

Modulation of the morphotropic phase boundary for high-performance ductile thermoelectric materials.

The flexible thermoelectric technique, which can convert heat from the human body to electricity via the Seebeck effect, is expected to provide a peerless solution for the power supply of wearables. The recent discovery of ductile semiconductors has opened a new avenue for flexible thermoelectric technology, but their power factor and figure-of-merit values are still much lower than those of classic thermoelectric materials. Herein, we demonstrate the presence of morphotropic phase boundary in Ag2Se-Ag2S pseudobinary compounds. The morphotropic phase boundary can be freely tuned by adjusting the material thermal treatment processes. High-performance ductile thermoelectric materials with excellent power factor (22 µWcm-1 K-2) and figure-of-merit (0.61) values are realized near the morphotropic phase boundary at 300 K. These materials perform better than all existing ductile inorganic semiconductors and organic materials. Furthermore, the in-plane flexible thermoelectric device based on these high-performance thermoelectric materials demonstrates a normalized maximum power density reaching 0.26 Wm-1 under a temperature gradient of 20 K, which is at least two orders of magnitude higher than those of flexible organic thermoelectric devices. This work can greatly accelerate the development of flexible thermoelectric technology.

Advancing Social and Environmental Research in Cancer Registries Using Geomasking for Address-Level Data.

Understanding the social and environmental causes of cancer in the United States, particularly in marginalized communities, is a major research priority. Population-based cancer registries are essential for advancing this research, given their nearly complete capture of incident cases within their catchment areas. Most registries limit the release of address-level geocodes linked to cancer outcomes to comply with state health departmental regulations. These policies ensure patient privacy, uphold data confidentiality, and enhance trust in research. However, these restrictions also limit the conduct of high-quality epidemiologic studies on social and environmental factors that may contribute to cancer burden. Geomasking refers to computational algorithms that distort locational data to attain a balance between effectively "masking" the original address location while faithfully maintaining the spatial structure in the data. We propose that the systematic deployment of scalable geomasking algorithms could accelerate research on social and environmental contributions across the cancer continuum by reducing measurement error bias while also protecting privacy. We encourage multidisciplinary teams of registry officials, geospatial analysts, cancer researchers, and others engaged in this form of research to evaluate and apply geomasking procedures based on feasibility of implementation, accuracy, and privacy protection to accelerate population-based research on social and environmental causes of cancer.

Diagnostic value of combined magnetic resonance imaging techniques in the evaluation of Parkinson disease.

Background: The incidence of Parkinson disease (PD) has been increasing each year. The development of new magnetic resonance imaging (MRI) technology can help understand its pathogenesis and identify more effective imaging-based biological indicators. Methods: The clinical and MRI imaging data of 40 patients with PD and 40 healthy controls were analyzed. All participants underwent susceptibility-weighted imaging (SWI), neuromelanin-sensitive magnetic resonance imaging (NM-MRI), and T2*mapping sequence examination. The diagnostic value of single and combined multiparameter indicators was analyzed using the receiver operating characteristic curve. Results: Compared with the healthy control group, the PD group showed significant differences in the disappearance of bilateral "swallow tail sign", the distribution volume of melanocytes in the substantia nigra and the smaller volume in the bilateral substantia nigra, the maximum signal of the locus coeruleus and the smaller and average volume in the bilateral substantia nigra, and the values of T2* and R2* in the bilateral substantia nigra (P<0.01). The maximum and smaller value and the average value of the bilateral locus coeruleus signal were negatively correlated with the disease course duration (P<0.05), and the smaller distribution volume of the melanin neurons in the bilateral substantia nigra was negatively correlated with Hoehn and Yahr (H-Y) grade (P<0.05). In the joint diagnosis with multiple indicators, some composite parameters were found to be negatively correlated with H-Y grading (P<0.05), while others were negatively correlated with disease course duration (P<0.05). Joint use of multiple parameter indicators greatly improved diagnostic efficacy [area under the curve (AUC) =0.958]. Conclusions: The distribution volume of melanin in substantia nigra and the maximum value of locus coeruleus signal may be the biological imaging indicators for the early diagnosis, severity, and follow-up evaluation of PD. Compared with a single indicator, composite indicators used in combination with multiple techniques have a significantly better diagnostic efficacy for PD.

Direct Observation of Enhanced Electron-Phonon Coupling in Copper Nanoparticles in the Warm-Dense Matter Regime.

Warm dense matter (WDM) represents a highly excited state that lies at the intersection of solids, plasmas, and liquids and that cannot be described by equilibrium theories. The transient nature of this state when created in a laboratory, as well as the difficulties in probing the strongly coupled interactions between the electrons and the ions, make it challenging to develop a complete understanding of matter in this regime. In this work, by exciting isolated ∼8 nm copper nanoparticles with a femtosecond laser below the ablation threshold, we create uniformly excited WDM. Using photoelectron spectroscopy, we measure the instantaneous electron temperature and extract the electron-ion coupling of the nanoparticle as it undergoes a solid-to-WDM phase transition. By comparing with state-of-the-art theories, we confirm that the superheated nanoparticles lie at the boundary between hot solids and plasmas, with associated strong electron-ion coupling. This is evidenced both by a fast energy loss of electrons to ions, and a strong modulation of the electron temperature induced by strong acoustic breathing modes that change the nanoparticle volume. This work demonstrates a new route for experimental exploration of the exotic properties of WDM.

Bipolaronic Nature of the Pseudogap in Quasi-One-Dimensional (TaSe4)2I Revealed via Weak Photoexcitation.

The origin of the pseudogap in many strongly correlated materials has been a longstanding puzzle. Here, we present experimental evidence that many-body interactions among small Holstein polarons, i.e., the formation of bipolarons, are primarily responsible for the pseudogap in (TaSe4)2I. After weak photoexcitation of the material, we observe the appearance of both dispersive (single-particle bare band) and flat bands (single-polaron sub-bands) in the gap by using time- and angle-resolved photoemission spectroscopy. Based on Monte Carlo simulations of the Holstein model, we propose that the melting of pseudogap and emergence of new bands originate from a bipolaron to single-polaron crossover. We also observe dramatically different relaxation times for the excited in-gap states in (TaSe4)2I (∼600 fs) compared with another 1D material Rb0.3MoO3 (∼60 fs), which provides a new method for distinguishing between pseudogaps induced by polaronic or Luttinger-liquid many-body interactions.

Linking Gba1 E326K mutation to microglia activation and mild age-dependent dopaminergic Neurodegeneration.

Mutations in the GBA1 gene have been identified as a prevalent genetic risk factor for Parkinson's disease (PD). GBA1 mutations impair enzymatic activity, leading to lysosomal dysfunction and elevated levels of α-synuclein (α-syn). While most research has primarily focused on GBA1's role in promoting synucleinopathy, emerging evidence suggests that neuroinflammation may be a key pathogenic alteration caused by GBA1 deficiency. To examine the molecular mechanism underlying GBA1 deficiency-mediated neuroinflammation, we generated Gba1 E326K knock-in (KI) mice using the CRISPR/Cas9 technology, which is linked to an increased risk of PD and dementia with Lewy bodies (DLB). In the ventral midbrain and hippocampus of 24-month-old Gba1 E326K KI mice, we found a moderate decline in GBA1 enzymatic activity, a buildup of glucosylceramide, and an increase in microglia density. Furthermore, we observed increased levels of pro-inflammatory cytokines and formation of reactive astrocytes in primary microglia and astrocytes, respectively, cultured from Gba1 E326K KI mice following treatment with pathologic α-syn preformed fibrils (PFF). Additionally, the gut inoculation of α-syn PFF in Gba1 E326K KI mice significantly enhanced the accumulation of Lewy bodies in the dentate gyrus of the hippocampus, accompanied by aggravated neuroinflammation and exacerbated non-motor symptoms. This research significantly enhances our understanding of the Gba1 E326K mutation's involvement in neuroinflammation and the cell-to-cell transmission of pathogenic α-syn in the brain, thereby opening new therapeutic avenues.