Giant pyroelectricity in nanomembranes.

Pyroelectricity describes the generation of electricity by temporal temperature change in polar materials1-3. When free-standing pyroelectric materials approach the 2D crystalline limit, how pyroelectricity behaves remained largely unknown. Here, using three model pyroelectric materials whose bonding characters along the out-of-plane direction vary from van der Waals (In2Se3), quasi-van der Waals (CsBiNb2O7) to ionic/covalent (ZnO), we experimentally show the dimensionality effect on pyroelectricity and the relation between lattice dynamics and pyroelectricity. We find that, for all three materials, when the thickness of free-standing sheets becomes small, their pyroelectric coefficients increase rapidly. We show that the material with chemical bonds along the out-of-plane direction exhibits the greatest dimensionality effect. Experimental observations evidence the possible influence of changed phonon dynamics in crystals with reduced thickness on their pyroelectricity. Our findings should stimulate fundamental study on pyroelectricity in ultra-thin materials and inspire technological development for potential pyroelectric applications in thermal imaging and energy harvesting.

The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer's disease.

Innate immunity is associated with Alzheimer's disease1, but the influence of immune activation on the production of amyloid-ß is unknown2,3. Here we identify interferon-induced transmembrane protein 3 (IFITM3) as a γ-secretase modulatory protein, and establish a mechanism by which inflammation affects the generation of amyloid-ß. Inflammatory cytokines induce the expression of IFITM3 in neurons and astrocytes, which binds to γ-secretase and upregulates its activity, thereby increasing the production of amyloid-ß. The expression of IFITM3 is increased with ageing and in mouse models that express familial Alzheimer's disease genes. Furthermore, knockout of IFITM3 reduces γ-secretase activity and the formation of amyloid plaques in a transgenic mouse model (5xFAD) of early amyloid deposition. IFITM3 protein is upregulated in tissue samples from a subset of patients with late-onset Alzheimer's disease that exhibit higher γ-secretase activity. The amount of IFITM3 in the γ-secretase complex has a strong and positive correlation with γ-secretase activity in samples from patients with late-onset Alzheimer's disease. These findings reveal a mechanism in which γ-secretase is modulated by neuroinflammation via IFITM3 and the risk of Alzheimer's disease is thereby increased.

Eye Care in Federally Qualified Health Centers.

PURPOSE: To assess changes in vision care availability at Federally Qualified Health Centers (FQHCs) between 2017 and 2021 and whether neighborhood-level demographic social risk factors (SRFs) associated with eye care services provided by FQHCs. DESIGN: Secondary data analysis of the Health Resources and Services Administration (HRSA) data and 2017-2021 American Community Survey (ACS). PARTICIPANTS: Federally Qualified Health Centers. METHODS: Patient and neighborhood characteristics for SRFs were summarized. Differences in FQHCs providing and not providing vision care were compared via Wilcoxon-Mann-Whitney tests for continuous measures and chi-square tests for categorical measures. Logistic regression models were used to test the associations between neighborhood measures and FQHCs providing vision care, adjusted for patient characteristics. MAIN OUTCOME MEASURES: Odds ratios (ORs) with 95% confidence intervals (CIs) for neighborhood-level predictors of FQHCs providing vision care services. RESULTS: Overall, 28.5% of FQHCs (n = 375/1318) provided vision care in 2017 versus 32% (n = 435/1362) in 2021 with some increases and decreases in both the number of FQHCs and those with and without vision services. Only 2.6% of people who accessed FQHC services received eye care in 2021. Among the 435 FQHCs that provided vision care in 2021, 27.1% (n = 118) had added vision services between 2017 and 2021, 71.5% (n = 311) had been offering vision services since at least 2017, and 1.4% (n = 6) were newly established. FQHCs providing vision care in 2021 were more likely to be in neighborhoods with a higher percentage of Hispanic/Latino individuals (OR, 1.08, 95% CI, 1.02-1.14, P = 0.0094), Medicaid-insured individuals (OR, 1.08, 95% CI, 1.02-1.14, P = 0.0120), and no car households (OR, 1.07, 95% CI, 1.01-1.13, P = 0.0142). However, FQHCs with vision care, compared to FQHCs without vision care, served a lower percentage of Hispanic/Latino individuals (27.2% vs. 33.9%, P = 0.0007), Medicaid-insured patients (42.8% vs. 46.8%, P < 0.0001), and patients living at or below 100% of the federal poverty line (61.3% vs. 66.3%, P < 0.0001). CONCLUSIONS: Vision care services are available at a few FQHCs, localized to a few states. Expanding eye care access at FQHCs would meet patients where they seek care to mitigate vision loss to underserved communities. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Relationship between Unstable Housing, Food Insecurity, and Vision Status in the MI-SIGHT Community Eye Disease Screening Program.

PURPOSE: Assess rate of visual impairment (VI) from uncorrected refractive error (URE) and associations with demographic and socioeconomic factors among low-income patients presenting to the Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine (MI-SIGHT) program. DESIGN: Cross-sectional study. PARTICIPANTS: Adults ≥ 18 years without acute ocular symptoms. METHODS: MI-SIGHT program participants received a telemedicine-based eye disease screening and ordered glasses through an online optical shop. Participants were categorized based on refractive error (RE) status: VI from URE (presenting visual acuity [PVA] ≤ 20/50, best corrected visual acuity [BCVA] ≥ 20/40), URE without VI (PVA ≥ 20/40, had ≥ 2 lines of improvement to BCVA), and no or adequately corrected RE (PVA ≥ 20/40, < 2 line improvement to BCVA). Patient demographics, self-reported visual function, and satisfaction with glasses obtained through the program were compared between groups using analysis of variance, Kruskal-Wallis, chi-square, and Fisher exact testing. MAIN OUTCOME MEASURES: PVA, BCVA, and presence of VI (defined as PVA ≤ 20/50). RESULTS: Of 1171 participants enrolled in the MI-SIGHT program during the first year, the average age was 55.1 years (standard deviation = 14.5), 37.7% were male, 54.1% identified as Black, and 1166 (99.6%) had both PVA and BCVA measured. VI was observed in 120 (10.3%); 96 had VI from URE (8.2%), 168 (14.4%) had URE without VI, and 878 (75.3%) had no or adequately corrected RE. A smaller percentage of participants with VI from URE reported having a college degree and a larger percentage reported income < $10 000 compared to participants with no or adequately corrected RE (3.2% versus 14.2%, P = 0.02; 45.5% versus 21.6%, respectively, P < 0.0001. Visual function was lowest among participants with VI from URE, followed by those with URE without VI, and then those with no or adequately corrected RE (VFQ9 composite score 67.3 ± 19.6 versus 77.0 ± 14.4 versus 82.2 ± 13.3, respectively; P < 0.0001). 71.2% (n = 830) ordered glasses for an average cost of $36.80 ± $32.60; 97.7% were satisfied with their glasses. CONCLUSIONS: URE was the main cause of VI at 2 clinics serving low-income communities and was associated with reduced vision-related quality of life. An online optical shop with lower prices made eyeglasses accessible to low-income patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Meta-analysis and systematic review of the relationship between sex and the risk or incidence of poststroke aphasia and its types.

OBJECTIVE: To analyse and discuss the association of gender differences with the risk and incidence of poststroke aphasia (PSA) and its types, and to provide evidence-based guidance for the prevention and treatment of poststroke aphasia in clinical practice. DATA SOURCES: Embase, PubMed, Cochrane Library and Web of Science were searched from January 1, 2002, to December 1, 2023. STUDY SELECTION: Including the total number of strokes, aphasia, the number of different sexes or the number of PSA corresponding to different sex. DATA EXTRACTION: Studies with missing data, aphasia caused by nonstroke and noncompliance with the requirements of literature types were excluded. DATA SYNTHESIS: 36 papers were included, from 19 countries. The analysis of 168,259 patients with stroke and 31,058 patients with PSA showed that the risk of PSA was 1.23 times higher in female than in male (OR = 1.23, 95% CI = 1.19-1.29, P < 0.001), with a prevalence of PSA of 31% in men and 36% in women, and an overall prevalence of 34% (P < 0.001). Analysis of the risk of the different types of aphasia in 1,048 patients with PSA showed a high risk in females for global, broca and Wenicke aphasia, and a high risk in males for anomic, conductive and transcortical aphasia, which was not statistically significant by meta-analysis. The incidence of global aphasia (males vs. females, 29% vs. 32%) and broca aphasia (17% vs 19%) were higher in females, and anomic aphasia (19% vs 14%) was higher in males, which was statistically significant (P < 0.05). CONCLUSIONS: There are gender differences in the incidence and types of PSA. The risk of PSA in female is higher than that in male.

Contemporary multimodality non-invasive cardiac imaging protocols for tetralogy of Fallot.

Tetralogy of Fallot is the most prevalent cyanotic congenital heart disease, requiring lifelong multimodality non-invasive cardiac imaging, such as echocardiography, cardiothoracic computed tomography, and cardiac magnetic resonance imaging. As imaging techniques continuously evolve and are gradually integrated into clinical practice, there is a critical need to update multimodality imaging protocols. Over the last two decades, cardiothoracic computed tomography imaging techniques have advanced remarkably, significantly enhancing its role in evaluating patients with tetralogy of Fallot. In this review, we describe contemporary multimodality non-invasive cardiac imaging protocols for tetralogy of Fallot, emphasizing the expanding role of cardiothoracic computed tomography. Additionally, we present standardized reporting forms designed to facilitate the clinical adoption of these protocols.

A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment.

The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti-PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly.

Evaluation of Ground Pressure, Bearing Capacity, and Sinkage in Rigid-Flexible Tracked Vehicles on Characterized Terrain in Laboratory Conditions.

Trafficability gives tracked vehicles adaptability, stability, and propulsion for various purposes, including deep-sea research in rough terrain. Terrain characteristics affect tracked vehicle mobility. This paper investigates the soil mechanical interaction dynamics between rubber-tracked vehicles and sedimental soils through controlled laboratory-simulated experiments. Focusing on Bentonite and Diatom sedimental soils, which possess distinct shear properties from typical land soils, the study employs innovative user-written subroutines to characterize mechanical models linked to the RecurDyn simulation environment. The experiment is centered around a dual-tracked crawler, which in itself represents a fully independent vehicle. A new three-dimensional multi-body dynamic simulation model of the tracked vehicle is developed, integrating the moist terrain's mechanical model. Simulations assess the vehicle's trafficability and performance, revealing optimal slip ratios for maximum traction force. Additionally, a mathematical model evaluates the vehicle's tractive trafficability based on slip ratio and primary design parameters. The study offers valuable insights and a practical simulation modeling approach for assessing trafficability, predicting locomotion, optimizing design, and controlling the motion of tracked vehicles across diverse moist terrain conditions. The focus is on the critical factors influencing the mobility of tracked vehicles, precisely the sinkage speed and its relationship with pressure. The study introduces a rubber-tracked vehicle, pressure, and moisture sensors to monitor pressure sinkage and moisture, evaluating cohesive soils (Bentonite/Diatom) in combination with sand and gravel mixtures. Findings reveal that higher moisture content in Bentonite correlates with increased track slippage and sinkage, contrasting with Diatom's notable compaction and sinkage characteristics. This research enhances precision in terrain assessment, improves tracked vehicle design, and advances terrain mechanics comprehension for off-road exploration, offering valuable insights for vehicle design practices and exploration endeavors.

Approaching Temporal Dynamics in the Dimension-Level Associations Between Career Adaptability/Ambivalence and Internalizing Symptoms Among Chinese Adolescents Throughout Their High Middle School Years.

Despite the well-established associations between adolescents' internalizing symptoms and career development, it still remains unclear whether adolescents' internalizing symptoms are precursors or consequences of their career adaptability/ambivalence. Subtler nuance inherent within such association also await to be revealed, because internalizing symptoms and career development have been primarily treated as broad constructs, despite the multifaceted nature of both. To narrow such gaps, this study examined the potentially dynamic associations among career adaptability, career ambivalence, and internalizing symptoms using three-wave longitudinal data. The study collected data from 3196 Chinese adolescents (52.72% girls, mean age = 15.56 years, SD = 0.58) at Wave 1, with 2820 (attrition rate = 11.76%) participating in Wave 2 and 2568 (attrition rate = 8.93%) in Wave 3. The measurement invariance suggested that there were no significant differences across both waves and genders. This study approached associations at both broader construct levels and subtler dimension levels. Results of cross-lagged path models at broader construct levels demonstrated a unidirectional association between internalizing symptoms and career adaptability. Results of models at subtler dimension levels indicated a series of transactional links over time between career adaptability dimensions/ambivalence and depressive symptoms in particular. Career adaptability dimensions and career ambivalence predicted later anxiety symptoms rather than the reverse. Group model comparisons showed no difference across waves and genders. These findings shed light on the dynamic nature of the associations during adolescence between career adaptability/ambivalence and internalizing symptoms, particularly at subtler dimensional levels, which should be considered in relevant clinical and educational practices.

Incommensurately Modulated Structure in AgCuSe-Based Thermoelectric Materials for Intriguing Electrical, Thermal, and Mechanical Properties.

AgCuSe-based materials have attracted great attentions recently in thermoelectric (TE) field due to their extremely high electron mobility, ultralow lattice thermal conductivity, and abnormal "brittle-ductile" transition at room temperature. However, although the investigation on the crystal structure of AgCuSe low-temperature phase (named as ß-AgCuSe) was started more than half a century before, it is still in controversy yet, which greatly limits the understanding of its intriguing electrical, thermal, and mechanical performance. In this work, via adopting the advanced three-dimensional electron diffraction technique, this study finds that the AgCuSe-based materials crystalize in an incommensurately modulated structure with an orthorhombic Pmmn(0ß1/2)s00 superspace group. The local lattice distortion in the incommensurately modulated structure has weak effects on the conduction band minimum due to the delocalized and isotropic feature of Ag 5s states, leading to high carrier mobility. Likewise, the inhomogeneous, weak, and anisotropic Ag-Se bonds result in the high degree of anharmonicity and ultralow lattice thermal conductivity. Furthermore, alloying S in AgCuSe reinforces the interaction between the adjacent Ag-Se layers, yielding the "brittle-ductile" transition at room temperature. This work well interprets the structure-performance relationship of AgCuSe-based materials and sheds light on the future investigation of this class of promising TE materials.

Seeing Red: Associations between Historical Redlining and Present-Day Visual Impairment and Blindness.

PURPOSE: Redlining was a discriminatory housing policy in the United States that began in 1933 and denoted neighborhoods with high proportions of Black individuals as "undesirable" and a high risk for lending, which therefore excluded people from obtaining traditional insured mortgages to purchase a home. Simultaneously, realtors discouraged Black individuals from purchasing homes in predominantly non-Black neighborhoods. This resulted in decreased home ownership and wealth accumulation among Black individuals and neighborhoods with high proportions of Black individuals. This study investigated rates of visual impairment and blindness (VIB) in neighborhoods that at one time were graded for redlining. DESIGN: Secondary data analysis of American Community Survey data and historical grades for redlining. PARTICIPANTS: United States census tracts (CTs) from 2010 with historical grades for redlining. METHODS: One-way analysis of variance, Kruskal-Wallis test, chi-square test, and logistic regression modeling. MAIN OUTCOME MEASURES: The main outcome was CT percentage of residents reporting VIB and the association with historical grades for redlining. Grades were converted to numeric values (1 to 4, with higher values indicating worse grade) and aggregated over a CT based on the distribution of grades within to obtain a redlining score. Logistic regression was used to model the effect of redlining on the probability of having VIB. RESULTS: Eleven thousand six hundred sixty-eight CTs were analyzed. Logistic regression found that a 1-unit increase in average redlining score was associated with a 13.4% increased odds of VIB after controlling for CT measures of age, sex, people of color (any non-White race), state, and population size (odds ratio [OR], 1.134; 95% confidence interval [CI], 1.131-1.138; P < 0.001). Similar results were observed for an additional model that adjusted for the estimated percentage of Black residents within a CT (OR, 1.180; 95% CI, 1.177-1.183; P < 0.001). CONCLUSIONS: Historical government-sanctioned residential segregation through redlining was found to be associated with higher proportions of people living with VIB in these neighborhoods today. Understanding how neighborhood segregation impacts eye health is important for planning improved mechanisms of eye care delivery to mitigate health disparities. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Social Deprivation and the Risk of Screening Positive for Glaucoma in the MI-SIGHT Telemedicine-Based Glaucoma Detection Program.

PURPOSE: To assess whether increased poverty is associated with increased risk of screening positive for glaucoma or suspected glaucoma in a large public screening and intervention program. DESIGN: Cross-sectional study from 2020 to 2022. PARTICIPANTS: Adults ≥ 18 years old without acute ocular symptoms. METHODS: Michigan Screening and Intervention for Glaucoma and eye Health through Telemedicine (MI-SIGHT) program participants' sociodemographic characteristics and area deprivation index (ADI) values were summarized from the clinical sites, which included a free clinic and a Federally Qualified Health Center (FQHC). The ADI, a composite measure of neighborhood deprivation (range, 1-10; 10 is worst deprivation), was assigned on the basis of the participants' addresses. Group comparisons were performed via 2-sample t tests or Wilcoxon Mann-Whitney tests for continuous measures and chi-square tests or Fisher exact tests with Monte Carlo simulation for categorical measures; Holm adjustment was used for multiple comparisons. MAIN OUTCOME MEASURES: Risk factors for screening positive for glaucoma or suspected glaucoma. RESULTS: Of the 1171 enrolled participants, 1165 (99.5%) completed the screening: 34% at the free clinic and 66% at the FQHC. Participants were on average aged 55.1 ± 14.5 years, 62% were women, 54% self-reported as Black/African-American, 34% White, 10% Hispanic or Latino, and 70% earned < $30 000 annually. The mean ADI was 7.2 ± 3.1. The FQHC had higher (worse) ADI than the free clinic (free clinic: 4.5 ± 2.9, FQHC: 8.5 ± 2.1, P < 0.0001). One-quarter (24%) of participants screened positive for glaucoma or suspected glaucoma. Screening positive for glaucoma or suspected glaucoma was associated with being older (P = 0.01), identifying as Black/African-American (P = 0.0001), having an established eyecare clinician (P = 0.0005), and not driving a personal vehicle to the appointment (P = 0.001), which is a proxy for increased poverty. Participants who screened positive had worse ADI than those who screened negative (7.7 ± 2.8 vs. 7.0 ± 3.2, P = 0.002). A larger percentage of White participants screened positive at the FQHC compared with White participants at the free clinic (21.3% vs. 12.3%, P = 0.01). FQHC White participants had worse ADI than free clinic White participants (7.5 ± 2.5 vs. 3.7 ± 2.7, P < 0.0001). CONCLUSIONS: Personal poverty, assessed as not driving a personal vehicle to the appointment, and neighborhood-level poverty were both associated with increased rates of screening positive for glaucoma or suspected glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Fiber-integrated catenary ring-array metasurfaces for beam shaping.

Catenary is referred to as "the real mathematical and mechanical form" in the architectural field. Because of the unique phase control characteristic of the catenary, it has excellent ability in optical manipulation. Here, we propose an optical waveform conversion device based on optical fiber-integrated catenary ring-array metasurfaces. The device consists of a cascade structure of a single-mode fiber (SMF) and a graded-index fiber (GIF). At the GIF end, two kinds of catenary ring-array metasurfaces are introduced to realize beam shaping from Gaussian beam (GB) to Bessel beam. The device can selectively generate a focused or non-diffracting Bessel beam by changing the circular polarization state of the incident light. It is worth noting that under some parameters of the device, the output Bessel beam can break through the diffraction limit, which has potential applications in the fields of optical imaging, optical communication, and optical trapping.

Phenotypic Heterogeneity in Patients with Mutations in the Mitochondrial Complex I Assembly Gene NDUFAF5.

BACKGROUND: Rare mutations in NADH:ubiquinone oxidoreductase complex assembly factor 5 (NDUFAF5) are linked to Leigh syndrome. OBJECTIVE: We aimed to describe clinical characteristics and functional findings in a patient cohort with NDUFAF5 mutations. METHODS: Patients with biallelic NDUFAF5 mutations were recruited from multi-centers in Taiwan. Clinical, laboratory, radiological, and follow-up features were recorded and mitochondrial assays were performed in patients' skin fibroblasts. RESULTS: Nine patients from seven unrelated pedigrees were enrolled, eight homozygous for c.836 T > G (p.Met279Arg) in NDUFAF5 and one compound heterozygous for p.Met279Arg. Onset age had a bimodal distribution. The early-onset group (age <3 years) presented with psychomotor delay, seizure, respiratory failure, and hyponatremia. The late-onset group (age ≥5 years) presented with normal development, but slowly progressive dystonia. Combing 25 previously described patients, the p.Met279Arg variant was exclusively identified in Chinese ancestry. Compared with other groups, patients with late-onset homozygous p.Met279Arg were older at onset (P = 0.008), had less developmental delay (P = 0.01), less hyponatremia (P = 0.01), and better prognosis with preserved ambulatory function into early adulthood (P = 0.01). Bilateral basal ganglia necrosis was a common radiological feature, but brainstem and spinal cord involvement was more common with early-onset patients (P = 0.02). A modifier gene analysis showed higher concomitant mutation burden in early-versus late-onset p.Met279Arg homozygous cases (P = 0.04), consistent with more impaired mitochondrial function in fibroblasts from an early-onset case than a late-onset patient. CONCLUSIONS: The p.Met279Arg variant is a common mutation in our population with phenotypic heterogeneity and divergent prognosis based on age at onset. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effect of Codeposition of Polydopamine with Polyethylenimine or Poly(ethylene glycol) Coatings on Silver Nanoparticle Synthesis.

This study investigated the effects of polydopamine (PDA), PDA/polyethylenimine (PEI), and PDA/poly(ethylene glycol) (PEG) deposition on silver nanoparticle (AgNP) formation. PEI or PEG with different molecular weights was mixed with dopamine at different concentrations to obtain various PDA/PEI or PDA/PEG codepositions. These codepositions were soaked in silver nitrate solution to observe AgNPs generated on the surface and then to examine the catalytic activity of AgNPs for the reduction of 4-nitrophenol to 4-aminophenol. Results revealed that AgNPs on PDA/PEI or PDA/PEG codepositions were smaller and more dispersed than those on PDA coatings. Codeposition with 0.5 mg/mL polymer and 2 mg/mL dopamine generated the smallest AgNPs in each codeposition system. The content of AgNPs on PDA/PEI codeposition first increased and then decreased with an increase in the PEI concentration. PEI with a molecular weight of 600 (PEI600) generated a higher AgNP content than did PEI with a molecular weight of 10000. The AgNP content did not change with the concentration and molecular weight of PEG. Except for the codeposition with 0.5 mg/mL PEI600, codepositions produced less silver than did the PDA coating. The catalytic activity of AgNPs on all codepositions was better than that on PDA. The catalytic activity of AgNPs on all codepositions was related to the size of AgNPs. Smaller AgNPs exhibited more satisfactory catalytic activity. The codeposition with 0.5 mg/mL PEI600 had the highest rate constant (1.64 min-1). The systematic study provides insight into the relationship between various codepositions and AgNP generation and demonstrates that the composition of these codepositions can be tuned to increase their applicability.

Salinimicrobium profundisediminis sp. nov., isolated from deep-sea sediment of the Mariana Trench.

A Gram-stain-negative, aerobic, rod-shaped, non-gliding bacterial strain, designated as MT39T, was isolated from a deep-sea sediment sample collected from the Mariana Trench. Strain MT39T grew optimally at 35°C and pH 7.0, and could tolerate up to 10% (w/v) NaCl. The strain was positive for catalase and negative for oxidase. The genome of strain MT39T was 4 033 307 bp, with a 41.1 mol % genomic G+C content and 3514 coding sequences. Phylogenetic analysis based on 16S rRNA gene sequences placed strain MT39T within the genus Salinimicrobium, showing the highest 16S rRNA gene sequence similarity to Salinimicrobium terrea CGMCC 1.6308T (98.1%). The average nucleotide identity and in silico DNA-DNA hybridization values between strain MT39T and the type strains of seven Salinimicrobium species were all less than the threshold values to discriminate bacterial species, indicating that strain MT39T is affiliated with a novel species within the genus. The major cellular fatty acids of strain MT39T were iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH. Polar lipids of strain MT39T included phosphatidylethanolamine, one unidentified aminolipid and four unidentified lipids. Menaquinone-6 was the only respiratory quinone in strain MT39T. On the basis of the polyphasic data present in this study, strain MT39T represents a novel species of the genus Salinimicrobium, for which the name Salinimicrobium profundisediminis sp. nov. is proposed, with type strain being MT39T (=MCCC 1K07832T=KCTC 92381T).

Efficacy of transarterial chemoembolization with drug-eluting beads combined with systemic chemotherapy and targeted therapy in colorectal cancer liver metastasis.

BACKGROUND: Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. MATERIALS: We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. RESULTS: In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. CONCLUSION: The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

How frequency hopping suppresses pulse-echo ambiguity in bat biosonar.

Big brown bats transmit wideband FM biosonar sounds that sweep from 55 to 25 kHz (first harmonic, FM1) and from 110 to 50 kHz (second harmonic, FM2). FM1 is required to perceive echo delay for target ranging; FM2 contributes only if corresponding FM1 frequencies are present. We show that echoes need only the lowest FM1 broadcast frequencies of 25 to 30 kHz for delay perception. If these frequencies are removed, no delay is perceived. Bats begin echo processing at the lowest frequencies and accumulate perceptual acuity over successively higher frequencies, but they cannot proceed without the low-frequency starting point in their broadcasts. This reveals a solution to pulse-echo ambiguity, a serious problem for radar or sonar. In dense, extended biosonar scenes, bats have to emit sounds rapidly to avoid collisions with near objects. But if a new broadcast is emitted when echoes of the previous broadcast still are arriving, echoes from both broadcasts intermingle, creating ambiguity about which echo corresponds to which broadcast. Frequency hopping by several kilohertz from one broadcast to the next can segregate overlapping narrowband echo streams, but wideband FM echoes ordinarily do not segregate because their spectra still overlap. By starting echo processing at the lowest frequencies in frequency-hopped broadcasts, echoes of the higher hopped broadcast are prevented from being accepted by lower hopped broadcasts, and ambiguity is avoided. The bat-inspired spectrogram correlation and transformation (SCAT) model also begins at the lowest frequencies; echoes that lack them are eliminated from processing of delay and no longer cause ambiguity.

Thinner biological tissues induce leaflet flutter in aortic heart valve replacements.

Valvular heart disease has recently become an increasing public health concern due to the high prevalence of valve degeneration in aging populations. For patients with severely impacted aortic valves that require replacement, catheter-based bioprosthetic valve deployment offers a minimally invasive treatment option that eliminates many of the risks associated with surgical valve replacement. Although recent percutaneous device advancements have incorporated thinner, more flexible biological tissues to streamline safer deployment through catheters, the impact of such tissues in the complex, mechanically demanding, and highly dynamic valvular system remains poorly understood. The present work utilized a validated computational fluid-structure interaction approach to isolate the behavior of thinner, more compliant aortic valve tissues in a physiologically realistic system. This computational study identified and quantified significant leaflet flutter induced by the use of thinner tissues that initiated blood flow disturbances and oscillatory leaflet strains. The aortic flow and valvular dynamics associated with these thinner valvular tissues have not been previously identified and provide essential information that can significantly advance fundamental knowledge about the cardiac system and support future medical device innovation. Considering the risks associated with such observed flutter phenomena, including blood damage and accelerated leaflet deterioration, this study demonstrates the potentially serious impact of introducing thinner, more flexible tissues into the cardiac system.

Genome-wide methylomic regulation of multiscale gene networks in Alzheimer's disease.

INTRODUCTION: Recent studies revealed the association of abnormal methylomic changes with Alzheimer's disease (AD) but there is a lack of systematic study of the impact of methylomic alterations over the molecular networks underlying AD. METHODS: We profiled genome-wide methylomic variations in the parahippocampal gyrus from 201 post mortem control, mild cognitive impaired, and AD brains. RESULTS: We identified 270 distinct differentially methylated regions (DMRs) associated with AD. We quantified the impact of these DMRs on each gene and each protein as well as gene and protein co-expression networks. DNA methylation had a profound impact on both AD-associated gene/protein modules and their key regulators. We further integrated the matched multi-omics data to show the impact of DNA methylation on chromatin accessibility, which further modulates gene and protein expression. DISCUSSION: The quantified impact of DNA methylation on gene and protein networks underlying AD identified potential upstream epigenetic regulators of AD. HIGHLIGHTS: A cohort of DNA methylation data in the parahippocampal gyrus was developed from 201 post mortem control, mild cognitive impaired, and Alzheimer's disease (AD) brains. Two hundred seventy distinct differentially methylated regions (DMRs) were found to be associated with AD compared to normal control. A metric was developed to quantify methylation impact on each gene and each protein. DNA methylation was found to have a profound impact on not only the AD-associated gene modules but also key regulators of the gene and protein networks. Key findings were validated in an independent multi-omics cohort in AD. The impact of DNA methylation on chromatin accessibility was also investigated by integrating the matched methylomic, epigenomic, transcriptomic, and proteomic data.