Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body mass, we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified five genes, important for tumor suppression, adaptive immunity, metastasis, and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of approximately 1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel "ape-specific" enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus. In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates.

Reducing leakage current and enhancing polarization in multiferroic 3D super-nanocomposites by microstructure engineering.

Multiferroic materials have generated great interest due to their potential as functional device materials. Nanocomposites have been increasingly used to design and generate new functionalities by pairing dissimilar ferroic materials, though the combination often introduces new complexity and challenges unforeseeable in single-phase counterparts. The recently developed approaches to fabricate 3D super-nanocomposites (3D-sNC) open new avenues to control and enhance functional properties. In this work, we develop a new 3D-sNC with CoFe2O4(CFO) short nanopillar arrays embedded in BaTiO3(BTO) film matrix via microstructure engineering by alternatively depositing BTO:CFO vertically-aligned nanocomposite layers and single-phase BTO layers. This microstructure engineering method allows encapsulating the relative conducting CFO phase by the insulating BTO phase, which suppress the leakage current and enhance the polarization. Our results demonstrate that microstructure engineering in 3D-sNC offers a new bottom-up method of fabricating advanced nanostructures with a wide range of possible configurations for applications where the functional properties need to be systematically modified.

Multifunctional Metal-Oxide Nanocomposite Thin Film with Plasmonic Au Nanopillars Embedded in Magnetic La0.67Sr0.33MnO3 Matrix.

Searching for multifunctional materials with tunable magnetic and optical properties has been a critical task toward the implementation of future integrated optical devices. Vertically aligned nanocomposite (VAN) thin films provide a unique platform for multifunctional material designs. Here, a new metal-oxide VAN has been designed with plasmonic Au nanopillars embedded in a ferromagnetic La0.67Sr0.33MnO3 (LSMO) matrix. Such Au-LSMO nanocomposite presents intriguing plasmon resonance in the visible range and magnetic anisotropy property, which are functionalized by the Au and LSMO phase, respectively. Furthermore, the vertically aligned nanostructure of metal and dielectric oxide results in the hyperbolic property for near-field electromagnetic wave manipulation. Such optical and magnetic response could be further tailored by tuning the composition of Au and LSMO phases.

Computed tomography angiography with 3D reconstruction in diagnosis of hydronephrosis cause by aberrant renal vessel: A case report and mini review.

BACKGROUND: Congenital hydronephrosis is often caused by aberrant renal vessel and it is difficult to be diagnosed and treated at the early stage due to lack of the significant symptoms. Although current medical diagnosis tools are widely used, the aberrant renal vessel cannot be displayed very well in the images. OBJECTIVE: To investigate whether applying computed tomography (CT) angiography with 3D reconstruction can improve efficacy in diagnose of this congenital hydronephrosis. MATERIALS AND METHODS: A male patient of 18 years old was diagnosed as hydronephrosis of left kidney. A CT angiography with 3D reconstruction was evaluated in diagnosis of the prenatal hydronephrosis compared to ultrasound (US) and intravenous urogram (IVU). RESULTS: US and IVU images were able to display the dilation of left pelvic and the dilated calyces, and the thinner of renal parenchyma on the left kidney (Grade II-IV), but failed to detect the causing of hydro-nephrosis. CT angiography with 3D reconstruction provided accurate images of the dilated renal pelvic, upper segment of the ureter, and an aberrant vessel bundle overcrossing at the left renal pelvic-ureter junction as well. The aberrant vessel could be revealed during surgery. CONCLUSIONS: A CT angiography with 3D reconstruction provides a more accurate diagnostic approach for the congenital hydronephrosis caused by aberrant renal vessel. Thus, it can offer surgeons very important information in the pre-surgery planning.

A case report of Rosai-Dorfman disease with kidney involvement.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder of unclear etiology, which commonly presented with the enlargement of lymph nodes of the neck and the head. Here, we report an unusual case of 77-year-old male patient presenting with left kidney lesion with several small enlarged lymph nodes around the abdominal aorta. The diagnosis of left kidney cancer was suspected and the patient underwent left laparoscopic exploration and lymph node biopsy. Only saponification of the renal surrounding fat and enlargement of the left renal pedicle and 5 abdominal aortic lymph nodes were found; no kidney cancer was found. Surrenalectomy and lymphadenectomy dissection were then performed and the left kidney was retained. Intraoperative frozen and postoperative pathology indicates Rosai-Dorfman disease. RDD with kidney involvement is uncommon, and its x-ray imaging appearances are atypical, and often resemble kidney cancer leading to kidney loss. A systematic literature review was also performed to investigate the x-ray imaging and treatment features of this disease.

Interatrial Wall Abnormality is Associated with Adverse Same-Admission Outcomes Following Total Knee Arthroplasty.

Total knee arthroplasty (TKA) is the most common joint arthroplasty procedure and is shown to be a reliable and efficacious way to improve quality of life. Individuals with interatrial wall abnormalities (IAWAs), such as atrial septal defect or patent foramen ovale (PFO), are at increased baseline risk for stroke and overall lifetime morbidity. The purpose of our study was to elucidate the association between IAWAs and perioperative TKA outcomes.We performed a retrospective cohort study utilizing the Healthcare Cost and Utilization Project National Inpatient Sample database. Admissions for TKA between 2010 and 2019 were identified using the international classification of disease (ICD)-9 and ICD-10 procedure codes. Patients with ICD-9-clinical modification (CM) diagnosis code 7455 or ICD-10-CM diagnosis code Q211 were assigned to the IAWA cohort, the primary exposure. Confounding variables included basic demographics, baseline health status, and surgical facility characteristics. The primary outcomes studied were medical complications, implant-related complications, and admission mortality. Univariate and adjusted multivariable regression analyses were used to identify associations.Compared to patients in the non-IAWA cohort, those in the IAWA cohort had significant risks for same-admission medical complications (odds ratio [OR] 5.77, 95% confidence interval [CI] 4.59-7.15; p < 0.001), implant-related complications (OR 1.55, 95% CI 1.09-2.12; p = 0.009), stroke (OR 77.46, 95% CI 58.4-101.2; p < 0.001), venous thromboembolism (VTE; OR 3.78 95% CI 2.47-5.51; p < 0.001), and mortality (OR 8.36, 95% CI 3.54-16.52; p < 0.001) following TKA.Compared to patients without IAWAs, those with IAWAs who undergo TKA have higher risks for same-admission medical and implant-related complications as well as same-admission mortality. Similarly, these patients have higher risks for same-admission stroke and VTE. Further research on perioperative TKA management in patients with IAWAs is needed.Level of Evidence is III: retrospective cohort study.

Characterization of Effects of mTOR Inhibitors on Aging in Caenorhabditis elegans.

Pharmacological inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway with rapamycin can extend lifespan in several organisms. Although this includes the nematode Caenorhabditis elegans, effects in this species are relatively weak and sometimes difficult to reproduce. Here we test effects of drug dosage and timing of delivery to establish the upper limits of its capacity to extend life, and investigate drug effects on age-related pathology and causes of mortality. Liposome-mediated rapamycin treatment throughout adulthood showed a dose-dependent effect, causing a maximal 21.9% increase in mean lifespan, but shortening of lifespan at the highest dose, suggesting drug toxicity. Rapamycin treatment of larvae delayed development, weakly reduced fertility and modestly extended lifespan. By contrast, treatment initiated later in life robustly increased lifespan, even from Day 16 (or ~70 years in human terms). The rapalog temsirolimus extended lifespan similarly to rapamycin, but effects of everolimus were weaker. As in mouse, rapamycin had mixed effects on age-related pathologies, inhibiting one (uterine tumor growth) but not several others, suggesting a segmental antigeroid effect. These findings should usefully inform future experimental studies with rapamycin and rapalogs in C. elegans.

Improved resilience and proteostasis mediate longevity upon DAF-2 degradation in old age.

Little is known about the possibility of reversing age-related biological changes when they have already occurred. To explore this, we have characterized the effects of reducing insulin/IGF-1 signaling (IIS) during old age. Reduction of IIS throughout life slows age-related decline in diverse species, most strikingly in the nematode Caenorhabditis elegans. Here we show that even at advanced ages, auxin-induced degradation of DAF-2 in single tissues, including neurons and the intestine, is still able to markedly increase C. elegans lifespan. We describe how reversibility varies among senescent changes. While senescent pathologies that develop in mid-life were not reversed, there was a rejuvenation of the proteostasis network, manifesting as a restoration of the capacity to eliminate otherwise intractable protein aggregates that accumulate with age. Moreover, resistance to several stressors was restored. These results support several new conclusions. (1) Loss of resilience is not solely a consequence of pathologies that develop in earlier life. (2) Restoration of proteostasis and resilience by inhibiting IIS is a plausible cause of the increase in lifespan. And (3), most interestingly, some aspects of the age-related transition from resilience to frailty can be reversed to a certain extent. This raises the possibility that the effect of IIS and related pathways on resilience and frailty during aging in higher animals might possess some degree of reversibility.

C. elegans ageing is accelerated by a self-destructive reproductive programme.

In post-reproductive C. elegans, destructive somatic biomass repurposing supports production of yolk which, it was recently shown, is vented and can serve as a foodstuff for larval progeny. This is reminiscent of the suicidal reproductive effort (reproductive death) typical of semelparous organisms such as Pacific salmon. To explore the possibility that C. elegans exhibits reproductive death, we have compared sibling species pairs of the genera Caenorhabditis and Pristionchus with hermaphrodites and females. We report that yolk venting and constitutive, early pathology involving major anatomical changes occur only in hermaphrodites, which are also shorter lived. Moreover, only in hermaphrodites does germline removal suppress senescent pathology and markedly increase lifespan. This is consistent with the hypothesis that C. elegans exhibit reproductive death that is suppressed by germline ablation. If correct, this would imply a major difference in the ageing process between C. elegans and most higher organisms, and potentially explain the exceptional plasticity in C. elegans ageing.

Life Cycle Assessment on Environmental Sustainability of Food Processing.

Food processing represents a critical part of the food supply chain that converts raw materials into safe and nutritious food products with high quality. However, the fast-growing food processing industry has imposed enormous burdens on the environment. Life cycle assessment (LCA) is widely used for evaluating the sustainability of food systems; nonetheless, current attention mainly concentrates on the agricultural production stage. This article reviews recent LCA studies on dairy, fruits and vegetables, and beverage products, with a particular emphasis on their processing stage. The environmental impacts of various foods are summarized, and the hotspots in their processing lines as well as potential remediation strategies are highlighted. Moreover, an outlook on the environmental performance of nonthermal processing, modified atmosphere packaging, and active packaging is provided, and future research directions are recommended. This review enables quantitative assessments and comparisons to be made by food manufacturers that are devoted to implementing sustainable processing technologies.

Single-Step Fabrication of Au-Fe-BaTiO3 Nanocomposite Thin Films Embedded with Non-Equilibrium Au-Fe Alloyed Nanostructures.

Nanocomposite thin film materials present great opportunities in coupling materials and functionalities in unique nanostructures including nanoparticles-in-matrix, vertically aligned nanocomposites (VANs), and nanolayers. Interestingly the nanocomposites processed through a non-equilibrium processing method, e.g., pulsed laser deposition (PLD), often possess unique metastable phases and microstructures that could not achieve using equilibrium techniques, and thus lead to novel physical properties. In this work, a unique three-phase system composed of BaTiO3 (BTO), with two immiscible metals, Au and Fe, is demonstrated. By adjusting the deposition laser frequency from 2 Hz to 10 Hz, the phase and morphology of Au and Fe nanoparticles in BTO matrix vary from separated Au and Fe nanoparticles to well-mixed Au-Fe alloy pillars. This is attributed to the non-equilibrium process of PLD and the limited diffusion under high laser frequency (e.g., 10 Hz). The magnetic and optical properties are effectively tuned based on the morphology variation. This work demonstrates the stabilization of non-equilibrium alloy structures in the VAN form and allows for the exploration of new non-equilibrium materials systems and their properties that could not be easily achieved through traditional equilibrium methods.

Blocking LAIR1 signaling in immune cells inhibits tumor development.

The current immune checkpoint blockade therapy has been successful in treating some cancers but not others. New molecular targets and therapeutic approaches of cancer immunology need to be identified. Leukocyte associated immunoglobulin like receptor 1 (LAIR1) is an immune inhibitory receptor expressing on most immune cell types. However, it remains a question whether we can specifically and actively block LAIR1 signaling to activate immune responses for cancer treatment. Here we report the development of specific antagonistic anti-LAIR1 monoclonal antibodies and studied the effects of LAIR1 blockade on the anti-tumor immune functions. The anti-LAIR1 antagonistic antibody stimulated the activities of T cells, natural killer cells, macrophages, and dendritic cells in vitro. The single-cell RNA sequencing analysis of intratumoral immune cells in syngeneic human LAIR1 transgenic mice treated with control or anti-LAIR1 antagonist antibodies indicates that LAIR1 signaling blockade increased the numbers of CD4 memory T cells and inflammatory macrophages, but decreased those of pro-tumor macrophages, regulatory T cells, and plasmacytoid dendritic cells. Importantly, the LAIR1 blockade by the antagonistic antibody inhibited the activity of immunosuppressive myeloid cells and reactivated T cells from cancer patients in vitro and impeded tumor metastasis in a humanized mouse model. Blocking LAIR1 signaling in immune cells represents a promising strategy for development of anti-cancer immunotherapy.

Gross ways to live long: Parasitic worms as an anti-inflammaging therapy?

Evolutionary medicine argues that disease can arise because modern conditions do not match those in which we evolved. For example, a decline in exposure to commensal microbes and gastrointestinal helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders (the hygiene hypothesis). Accordingly, probiotic therapies that restore 'old friend' microbes and helminths have been explored as Darwinian treatments for these disorders. A further possibility is that loss of old friend commensals also increases the sterile, aging-associated inflammation known as inflammaging, which contributes to a range of age-related diseases, including cardiovascular disease, dementia, and cancer. Interestingly, Crowe et al., 2020 recently reported that treatment with a secreted glycoprotein from a parasitic nematode can protect against murine aging by induction of anti-inflammatory mechanisms. Here, we explore the hypothesis that restorative helminth therapy would have anti-inflammaging effects. Could worm infections provide broad-spectrum protection against age-related disease?

Hybrid Ag-LiNbO3 nanocomposite thin films with tailorable optical properties.

Ag nanostructures exhibit extraordinary optical properties, which are important for photonic device integration. Herein, we deposited Ag-LiNbO3 (LNO) nanocomposite thin films with Ag nanoparticles (NPs) embedded into the LNO matrix by the co-deposition of Ag and LNO using a pulsed laser deposition (PLD) method. The density and size of Ag NPs were tailored by varying the Ag composition. Low-density and high-density Ag-LNO nanocomposite thin films were deposited and their optical properties, such as transmittance spectra, ellipsometry measurement, as well as angle-dependent and polarization-resolved reflectivity spectra, were explored. The Ag-LNO films show surface plasmon resonance (SPR) in the visible range, tunable optical constants and optical anisotropy, which are critical for photonic device applications.

Effectiveness of Intrathecal Baclofen for Intractable Stiffperson Syndrome: a Case Report.

BACKGROUND: Intrathecal baclofen is considered an adjuvant therapy for patients with intractable spasms due to stiff-person syndrome. There is increasing evidence to support the use of intrathecal baclofen in the management of symptomatic stiffperson syndrome, with improvement in function. CASE REPORT: A 38-year-old woman with stiff- person syndrome initially presented to inpatient rehabilitation for intractable muscle spasms. The symptoms made her non-ambulatory and limited her tolerance to wheelchair use for mobility. The patient underwent up-titration of oral baclofen and diazepam, with concurrent intravenous immunoglobulin cycles, leading to transient symptom relief. She agreed to explore intrathecal baclofen therapy. An initial trial of a single bolus of 50 µg intrathecal baclofen resulted in a significant decrease in spontaneous spasms, enabling modified independence in transfers and ambulation. The patient was subsequently implanted with a permanent intrathecal delivery system. To date, the intrathecal baclofen had been titrated to 186 µg per day with simple continuous delivery. The patient was weaned off oral baclofen. She attained complete functional independence with ambulation without the need for assistive devices, and has had no lasting post-procedural complications to date. CONCLUSION: This case report adds to the increasing evidence of cases of refractory stiff-person syndrome managed successfully using intrathecal baclofen therapy.

Mutation of daf-2 extends lifespan via tissue-specific effectors that suppress distinct life-limiting pathologies.

In aging Caenorhabditis elegans, as in higher organisms, there is more than one cause of death. C. elegans exhibit early death with a swollen, infected pharynx (P death), and later death with pharyngeal atrophy (p death). Interventions that alter lifespan can differentially affect frequency and timing of each type of death, generating complex survival curve shapes. Here, we use mortality deconvolution analysis to investigate how reduction of insulin/IGF-1 signaling (IIS), which increases lifespan (the Age phenotype), affects different forms of death. All daf-2 insulin/IGF-1 receptor mutants exhibit increased lifespan in the p subpopulation (p Age), while pleiotropic class 2 daf-2 mutants show an additional marked reduction in P death frequency. The latter is promoted by pharyngeal expression of the IIS-regulated DAF-16 FOXO transcription factor, and at higher temperature by reduced pharyngeal pumping rate. Pharyngeal DAF-16 also promotes p Age in class 2 daf-2 mutants, revealing a previously unknown role for the pharynx in the regulation of aging. Necropsy analysis of daf-2 interactions with the daf-12 steroid receptor implies that previously described opposing effects of daf-12 on daf-2 longevity are attributable to internal hatching of larvae, rather than complex interactions between insulin/IGF-1 and steroid signaling. These findings support the view that wild-type IIS acts through multiple distinct mechanisms which promote different life-limiting pathologies, each of which contribute to late-life mortality. This study further demonstrates the utility of mortality deconvolution analysis to better understand the genetics of lifespan.

The Writers, Readers, and Erasers in Redox Regulation of GAPDH.

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH toward different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g., sulfenylation, S-thiolation, nitrosylation, and sulfhydration. These modifications alter the enzyme's conformation, subcellular localization, and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.

Ceramic Material Processing Towards Future Space Habitat: Electric Current-Assisted Sintering of Lunar Regolith Simulant.

In situ utilization of available resources in space is necessary for future space habitation. However, direct sintering of the lunar regolith on the Moon as structural and functional components is considered to be challenging due to the sintering conditions. To address this issue, we demonstrate the use of electric current-assisted sintering (ECAS) as a single-step method of compacting and densifying lunar regolith simulant JSC-1A. The sintering temperature and pressure required to achieve a relative density of 97% and microhardness of 6 GPa are 700 °C and 50 MPa, which are significantly lower than for the conventional sintering technique. The sintered samples also demonstrated ferroelectric and ferromagnetic behavior at room temperature. This study presents the feasibility of using ECAS to sinter lunar regolith for future space resource utilization and habitation.

Integration of highly anisotropic multiferroic BaTiO3-Fe nanocomposite thin films on Si towards device applications.

Integration of highly anisotropic multiferroic thin films on silicon substrates is a critical step towards low-cost devices, especially high-speed and low-power consumption memories. In this work, an oxide-metal vertically aligned nanocomposite (VAN) platform has been used to successfully demonstrate self-assembled multiferroic BaTiO3-Fe (BTO-Fe) nanocomposite films with high structural anisotropy on Si substrates. The effects of various buffer layers on the crystallinity, microstructure, and physical properties of the BTO-Fe films have been explored. With an appropriate buffer layer design, e.g. SrTiO3/TiN bilayer buffer, the epitaxial quality of the BTO matrix and the anisotropy of the Fe nanopillars can be improved greatly, which in turn enhances the physical properties, including the ferromagnetic, ferroelectric, and optical response of the BTO-Fe thin films. This unique combination of properties integrated on Si offers a promising approach in the design of multifunctional nanocomposites for Si-based memories and optical devices.

Strain Effects on the Growth of La0.7Sr0.3MnO3 (LSMO)-NiO Nanocomposite Thin Films via Substrate Control.

Oxide-oxide-based vertically aligned nanocomposites (VANs) have demonstrated a new material platform for enhanced and/or combined functionalities because of their unique vertical geometry and strain coupling. Various factors contribute to the growth of VANs, including deposition parameters, phase composition, phase ratios, crystallography, etc. In this work, substrate strain effects are explored through growing a two-phase oxide-oxide La0.7Sr0.3MnO3 (LSMO):NiO system, combining antiferromagnetic NiO and ferromagnetic LSMO, on various substrates with different lattice parameters. The X-ray diffraction (XRD), transmission electron microscopy (TEM), and magnetic property measurements all suggest that substrate strain plays a critical role in the epitaxial growth of a VAN structure and their two-phase separation, and thus results in different physical properties. This work sheds light on the fundamental nucleation and growth mechanisms of the two-phase VAN systems and the effects of substrate strain on the overall orientation and growth quality of the VAN films.