APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes.

APOE4 is the strongest genetic risk factor for Alzheimer's disease1-3. However, the effects of APOE4 on the human brain are not fully understood, limiting opportunities to develop targeted therapeutics for individuals carrying APOE4 and other risk factors for Alzheimer's disease4-8. Here, to gain more comprehensive insights into the impact of APOE4 on the human brain, we performed single-cell transcriptomics profiling of post-mortem human brains from APOE4 carriers compared with non-carriers. This revealed that APOE4 is associated with widespread gene expression changes across all cell types of the human brain. Consistent with the biological function of APOE2-6, APOE4 significantly altered signalling pathways associated with cholesterol homeostasis and transport. Confirming these findings with histological and lipidomic analysis of the post-mortem human brain, induced pluripotent stem-cell-derived cells and targeted-replacement mice, we show that cholesterol is aberrantly deposited in oligodendrocytes-myelinating cells that are responsible for insulating and promoting the electrical activity of neurons. We show that altered cholesterol localization in the APOE4 brain coincides with reduced myelination. Pharmacologically facilitating cholesterol transport increases axonal myelination and improves learning and memory in APOE4 mice. We provide a single-cell atlas describing the transcriptional effects of APOE4 on the aging human brain and establish a functional link between APOE4, cholesterol, myelination and memory, offering therapeutic opportunities for Alzheimer's disease.

Proksee: in-depth characterization and visualization of bacterial genomes.

Proksee (https://proksee.ca) provides users with a powerful, easy-to-use, and feature-rich system for assembling, annotating, analysing, and visualizing bacterial genomes. Proksee accepts Illumina sequence reads as compressed FASTQ files or pre-assembled contigs in raw, FASTA, or GenBank format. Alternatively, users can supply a GenBank accession or a previously generated Proksee map in JSON format. Proksee then performs assembly (for raw sequence data), generates a graphical map, and provides an interface for customizing the map and launching further analysis jobs. Notable features of Proksee include unique and informative assembly metrics provided via a custom reference database of assemblies; a deeply integrated high-performance genome browser for viewing and comparing analysis results at individual base resolution (developed specifically for Proksee); an ever-growing list of embedded analysis tools whose results can be seamlessly added to the map or searched and explored in other formats; and the option to export graphical maps, analysis results, and log files for data sharing and research reproducibility. All these features are provided via a carefully designed multi-server cloud-based system that can easily scale to meet user demand and that ensures the web server is robust and responsive.

Transmission of Alzheimer's disease-associated microbiota dysbiosis and its impact on cognitive function: evidence from mice and patients.

Spouses of Alzheimer's disease (AD) patients are at a higher risk of developing incidental dementia. However, the causes and underlying mechanism of this clinical observation remain largely unknown. One possible explanation is linked to microbiota dysbiosis, a condition that has been associated with AD. However, it remains unclear whether gut microbiota dysbiosis can be transmitted from AD individuals to non-AD individuals and contribute to the development of AD pathogenesis and cognitive impairment. We, therefore, set out to perform both animal studies and clinical investigation by co-housing wild-type mice and AD transgenic mice, analyzing microbiota via 16S rRNA gene sequencing, measuring short-chain fatty acid amounts, and employing behavioral test, mass spectrometry, site-mutations and other methods. The present study revealed that co-housing between wild-type mice and AD transgenic mice or administrating feces of AD transgenic mice to wild-type mice resulted in AD-associated gut microbiota dysbiosis, Tau phosphorylation, and cognitive impairment in the wild-type mice. Gavage with Lactobacillus and Bifidobacterium restored these changes in the wild-type mice. The oral and gut microbiota of AD patient partners resembled that of AD patients but differed from healthy controls, indicating the transmission of microbiota. The underlying mechanism of these findings includes that the butyric acid-mediated acetylation of GSK3ß at lysine 15 regulated its phosphorylation at serine 9, consequently impacting Tau phosphorylation. Pending confirmative studies, these results provide insight into a potential link between the transmission of AD-associated microbiota dysbiosis and development of cognitive impairment, which underscore the need for further research in this area.

Differential Interventional Effects of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on High Fat Diet-Induced Obesity and Hepatic Pathology.

Current Dietary Guidelines for Americans recommend replacing saturated fat (SFA) intake with polyunsaturated fatty acids (PUFAs) and monosaturated fatty acids (MUFAs) but do not specify the type of PUFAs, which consist of two functionally distinct classes: omega-6 (n-6) and omega-3 (n-3) PUFAs. Given that modern Western diets are already rich in n-6 PUFAs and the risk of chronic disease remains high today, we hypothesized that increased intake of n-3 PUFAs, rather than n-6 PUFAs, would be a beneficial intervention against obesity and related liver diseases caused by high-fat diets. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet (HF) for 10 weeks to induce obesity, then divided the obese mice into three groups and continued feeding for another 10 weeks with one of the following three diets: HF, HF+n-6 (substituted half of SFA with n-6 PUFAs), and HF+n-3 (substituted half of SFA with n-3 PUFAs), followed by assessment of body weight, fat mass, insulin sensitivity, hepatic pathology, and lipogenesis. Interestingly, we found that the HF+n-6 group, like the HF group, had a continuous increase in body weight and fat mass, while the HF+n-3 group had a significant decrease in body weight and fat mass, although all groups had the same calorie intake. Accordingly, insulin resistance and fatty liver pathology (steatosis and fat levels) were evident in the HF+n-6 and HF groups but barely seen in the HF+n-3 group. Furthermore, the expression of lipogenesis-related genes in the liver was upregulated in the HF+n-6 group but downregulated in the HF+n-3 group. Our findings demonstrate that n-6 PUFAs and n-3 PUFAs have differential effects on obesity and fatty liver disease and highlight the importance of increasing n-3 PUFAs and reducing n-6 PUFAs (balancing the n-6/n-3 ratio) in clinical interventions and dietary guidelines for the management of obesity and related diseases.

Increased lipogenesis is critical for self-renewal and growth of breast cancer stem cells: Impact of omega-3 fatty acids.

Aberrant lipid metabolism has recently been recognized as a new hallmark of malignancy, but the characteristics of fatty acid metabolism in breast cancer stem cells (BCSC) and potential interventions targeting this pathway remain to be addressed. Here, by using the in vitro BCSC models, mammosphere-derived MCF-7 cells and HMLE-Twist-ER cells, we found that the cells with stem cell-like properties exhibited a very distinct profile of fatty acid metabolism compared with that of their parental cancer cells, characterized by increased lipogenesis, especially the activity of stearoyl-CoA desaturase 1 (SCD1) responsible for the production of monounsaturated fatty acids, and augmented synthesis and utilization of the omega-6 arachidonic acid (AA). Suppression of SCD1 activity by either enzyme inhibitors or small interfering RNA (siRNA) knockdown strikingly limited self-renewal and growth of the BCSC, suggesting a key role for SCD1 in BCSC proliferation. Furthermore, elevated levels of SCD1 and other lipogenic enzymes were observed in human breast cancer tissues relative to the noncancer tissues from the same patients and correlated with the pathological grades. Interestingly, treatment of BCSC with omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, effectively downregulated the expression of the lipogenic enzymes and markedly suppressed BCSC self-renewal and growth. Dietary supplementation of nude mice bearing BCSC-derived tumors with omega-3 fatty acids also significantly reduced their tumor load. These findings have demonstrated that increased lipogenesis is critical for self-renewal and growth of BCSC, and that omega-3 fatty acids are effective in targeting this pathway to exert their anticancer effect.

Using real-time visualization system for data-driven decision support to achieve lung protective strategy: a retrospective observational study.

BACKGROUND: Although lung protective strategy and adjunctive intervention are associated with improved survival in patients with acute respiratory distress syndrome (ARDS), the implementation of effective therapies remains low. This study aimed to evaluate whether the use of business intelligence (BI) for real-time data visualization is associated with an improvement in lung protective strategy and adjunctive therapy. METHODS: A retrospective observational cohort study was conducted on patients with ARDS admitted between September 2020 and June 2021 at two intensive care units (ICUs) of a tertiary referral hospital in Taiwan. BI was imported for data visualization and integration to assist in clinical decision in one of the ICUs. The primary outcomes were the implementation of low tidal volume ventilation (defined as tidal volume/predicted body weight ≤ 8 mL/kg) within 24 h from ARDS onset. The secondary outcomes included ICU and hospital mortality rates. RESULTS: Among the 1201 patients admitted to the ICUs during the study period, 148 (12.3%) fulfilled the ARDS criteria, with 86 patients in the BI-assisted group and 62 patients in the standard-of-care (SOC) group. Disease severity was similar between the two groups. The application of low tidal volume ventilation strategy was significantly improved in the BI-assisted group compared with that in the SOC group (79.1% vs. 61.3%, p = 0.018). Despite their ARDS and disease severity, the BI-assisted group tended to achieve low tidal volume ventilation. The ICU and hospital mortality were lower in the BI-assisted group. CONCLUSIONS: The use of real-time visualization system for data-driven decision support was associated with significantly improved compliance to low tidal volume ventilation strategy, which enhanced the outcomes of patients with ARDS in the ICU.

Omega-3 Polyunsaturated Fatty Acids Protect against High-Fat Diet-Induced Morphological and Functional Impairments of Brown Fat in Transgenic Fat-1 Mice.

The role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the regulation of energy homeostasis remains poorly understood. In this study, we used a transgenic fat-1 mouse model, which can produce n-3 PUFAs endogenously, to investigate how n-3 PUFAs regulate the morphology and function of brown adipose tissue (BAT). We found that high-fat diet (HFD) induced a remarkable morphological change in BAT, characterized by "whitening" due to large lipid droplet accumulation within BAT cells, associated with obesity in wild-type (WT) mice, whereas the changes in body fat mass and BAT morphology were significantly alleviated in fat-1 mice. The expression of thermogenic markers and lypolytic enzymes was significantly higher in fat-1 mice than that in WT mice fed with HFD. In addition, fat-1 mice had significantly lower levels of inflammatory markers in BAT and lipopolysaccharide (LPS) in plasma compared with WT mice. Furthermore, fat-1 mice were resistant to LPS-induced suppression of UCP1 and PGC-1 expression and lipid deposits in BAT. Our data has demonstrated that high-fat diet-induced obesity is associated with impairments of BAT morphology (whitening) and function, which can be ameliorated by elevated tissue status of n-3 PUFAs, possibly through suppressing the effects of LPS on inflammation and thermogenesis.

Biocompatibility and Biological Performance of Additive-Manufactured Bioabsorbable Iron-Based Porous Interference Screws in a Rabbit Model: A 1-Year Observational Study.

This study evaluated the mid-term (12-month) biomechanical, biocompatibility, and biological performance of additive-manufactured bioabsorbable iron-based interference screws (ISs). Two bioabsorbable iron IS types-manufactured using pure iron powder (iron_IS) and using pure iron powder with 0.2 wt% tricalcium phosphate (TCP_IS)-were compared with conventional metallic IS (control) using in vitro biocompatibility and degradation analyses and an in vivo animal study. The in vitro ultimate failure strength was significantly higher for iron_IS and TCP_IS than for control ISs at 3 months post-operatively; however, the difference between groups were nonsignificant thereafter. Moreover, at 3 months after implantation, iron_IS and TCP_IS increased bone volume fraction, bone surface area fraction, and percent intersection surface; the changes thereafter were nonsignificant. Iron_IS and TCP_IS demonstrated degradation over time with increased implant surface, decreased implant volume, and structure thickness; nevertheless, the analyses of visceral organs and biochemistry demonstrated normal results, except for time-dependent iron deposition in the spleen. Therefore, compared with conventional ISs, bioabsorbable iron-based ISs exhibit higher initial mechanical strength. Although iron-based ISs demonstrate high biocompatibility 12 months after implantation, their corrosive iron products may accumulate in the spleen. Because they demonstrate mechanical superiority along with considerable absorption capability after implantation, iron-based ISs may have potential applications in implantable medical-device development in the future.

Pilot Report for Intracranial Hemorrhage Detection with Deep Learning Implanted Head Computed Tomography Images at Emergency Department.

Hemorrhagic stroke is a serious clinical condition that requires timely diagnosis. An artificial intelligence algorithm system called DeepCT can identify hemorrhagic lesions rapidly from non-contrast head computed tomography (NCCT) images and has received regulatory clearance. A non-controlled retrospective pilot clinical trial was conducted. Patients who received NCCT at the emergency department (ED) of Kaohsiung Veteran General Hospital were collected. From 2020 January-1st to April-30th, the physicians read NCCT images without DeepCT. From 2020May-1st to August-31st, the physicians were assisted by DeepCT. The length of ED stays (LOS) for the patients was collected. 2,999 patients were included (188 and 2811 with and without ICH). For patients with a final diagnosis of ICH, implementing DeepCT significantly shortened their LOS (560.67 ± 604.93 min with DeepCT vs. 780.83 ± 710.27 min without DeepCT; p = 0.0232). For patients with a non-ICH diagnosis, the LOS did not significantly differ (705.90 ± 760.86 min with DeepCT vs. 679.45 ± 681.97 min without DeepCT; p = 0.3362). For patients with ICH, those assisted with DeepCT had a significantly shorter LOS than those without DeepCT. For patients with a non-ICH diagnosis, implementing DeepCT did not affect the LOS, because emergency physicians need same efforts to identify the underlying problem(s) with or without DeepCT. In summary, implementing DeepCT system in the ED will save costs, decrease LOS, and accelerate patient flow; most importantly, it will improve the quality of care and increase the confidence and shorten the response time of the physicians and radiologists.

Natural Negative-Refractive-Index Materials.

Our calculation shows that negative refractive index (NRI), which was known to exist only in metamaterials in the past, can be found in Dirac semimetals (DSM). Electrons in DSM have zero effective mass and hence the system carries no nominal energy scale. Therefore, unlike those of ordinary materials, the electromagnetic responses of the electrons in DSM will not be overwhelmed by the physical effects related to electron mass. NRI is induced by the combination of the quantum effect of vacuum polarization and its finite temperature correction, which is proportional to T^{4} at low temperature. It is a phenomenon of resonance between the incident light and the unique structure of Dirac cones, which allows numerous states to participate in electron-hole pair production excited by the incident light with a similar dispersion relation to that of Dirac cones. The NRI phenomenon of DSM manifests in an extensive range of photon frequencies and wave numbers and can be observed around the gigahertz range at room temperature.

Identification of Specific Endobronchial Ultrasound Features to Differentiate Sarcoidosis From Other Causes of Lymphadenopathy.

OBJECTIVES: We hypothesized that specific endobronchial ultrasound (EBUS) features may differentiate sarcoidosis from other causes of lymphadenopathy. METHODS: We conducted this retrospective observational study from January 2014 to January 2019 to analyze patients with intrathoracic lymphadenopathy who underwent EBUS-guided transbronchial needle aspiration. Ultrasound features, including nodal size, margin, echogenicity, the presence or absence of calcification, a central hilar structure, the coagulation necrosis sign, nodal conglomeration, and the septal vessel sign in the color Doppler mode were recorded and compared between 3 groups. RESULTS: Of the 90 included patients, 15 had a diagnosis of tuberculosis; 56 had a diagnosis of sarcoidosis; and 19 had a diagnosis of malignant lymph nodes by EBUS-guided transbronchial needle aspiration. The presence of nodal conglomeration (94.6% versus 60.0% versus 5.3%; P < .001), the septal vessel sign in the color Doppler mode (55.4% versus 13.3% versus 15.8%; P = .002), and a distinct margin (73.2% versus 13.3% versus 47.4%; P < .001) were significantly higher in the sarcoidosis group than in the tuberculosis lymphadenopathy and malignant lymph node groups. The presence of the coagulation necrosis sign (8.9% versus 93.3% versus 31.6%; P < .001) was significantly lower in the sarcoidosis group than in tuberculosis lymphadenopathy and malignant lymph node groups. A multivariate analysis showed that the presence of nodal conglomeration, the absence of coagulation necrosis, and the presence of the septal vessel sign in the color Doppler mode were independent predictive factors for the diagnosis of sarcoidosis. CONCLUSIONS: The presence of nodal conglomeration, the absence of coagulation necrosis, and the presence of the septal vessel sign in the color Doppler mode in lymph nodes on EBUS are predictive of sarcoidosis.

Additive-manufactured Ti-6Al-4 V/Polyetheretherketone composite porous cage for Interbody fusion: bone growth and biocompatibility evaluation in a porcine model.

BACKGROUND: We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology. METHODS: Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40, 60, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed. RESULTS: Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60 and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group. CONCLUSION: The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.

Impact of the COVID-19 pandemic on emergency medical service response to out-of-hospital cardiac arrests in Taiwan: a retrospective observational study.

BACKGROUND: Emergency medical service (EMS) personnel have high COVID-19 risk during resuscitation. The resuscitation protocol for patients with out-of-hospital cardiac arrest (OHCA) was modified in response to the COVID-19 pandemic. However, how the adjustments in the EMS system affected patients with OHCA remains unclear. METHODS: We analysed data from the Taichung OHCA registry system. We compared OHCA outcomes and rescue records for 622 cases during the COVID-19 outbreak period (1 February to 30 April 2020) with those recorded for 570 cases during the same period in 2019. RESULTS: The two periods did not differ significantly with respect to patient age, patient sex, the presence of witnesses or OHCA location. Bystander cardiopulmonary resuscitation and defibrillation with automated external defibrillators were more common in 2020 (52.81% vs 65.76%, p<0.001%, and 23.51% vs 31.67%, p=0.001, respectively). The EMS response time was longer during the COVID-19 pandemic (445.8±210.2 s in 2020 vs 389.7±201.8 s in 2019, p<0.001). The rate of prehospital return of spontaneous circulation was lower in 2020 (6.49% vs 2.57%, p=0.001); 2019 and 2020 had similar rates of survival discharge (5.96% vs 4.98%). However, significantly fewer cases had favourable neurological function in 2020 (4.21% vs 2.09%, p=0.035). CONCLUSION: EMS response time for patients with OHCA was prolonged during the COVID-19 pandemic. Early advanced life support by EMS personnel remains crucial for patients with OHCA.

Biocompatibility and Biological Performance Evaluation of Additive-Manufactured Bioabsorbable Iron-Based Porous Suture Anchor in a Rabbit Model.

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.

Effect of bFGF on the growth and matrix turnover of stem cells from human apical papilla: Role of MEK/ERK signaling.

BACKGROUND/PURPOSE: Basic fibroblast growth factor (bFGF) exhibits multiple biological functions in various tissues. Stem cells from apical papilla (SCAP) can be isolated from human apical papilla tissues in developmental teeth of children. The purposes of this study were to investigate the expression of FGF receptors (FGFRs) and the effects of bFGF on SCAP and related MEK/ERK signaling. METHODS: SCAP cells were treated under different concentrations of bFGF with or without U0126 (an inhibitor of MEK/ERK). Expression of FGFR1 and FGFR2 in SCAP was analyzed by RT-PCR. Cell proliferation was measured by MTT assay. The expressions of type I collagen, cdc 2, cyclin B1, TIMP-1 and p-ERK proteins were examined by Western blot. RESULTS: SCAP cells expressed FGFR1 and FGFR2. Exposure of SCAP to bFGF enhanced cell proliferation, and the expression cyclinB1, cdc 2, and TIMP-1, but not type I collagen. U0126 pretreatment and co-incubation attenuated the bFGF-induced proliferation, cdc2, cyclin B1 and TIMP-1 proteins' expression, but not type I collagen in SCAP. CONCLUSION: SCAP cells express FGFRs. bFGF may stimulate proliferation and affect the matrix turnover of SCAP cells, possibly via stimulation of FGFRs and MEK/ERK signaling pathway. These results are useful for clinical therapies for apexogenesis and regeneration of pulpo-dentin complex.

Novel Insights into the Pathogenesis of Spinal Sarcopenia and Related Therapeutic Approaches: A Narrative Review.

Spinal sarcopenia is a complex and multifactorial disorder associated with a loss of strength, increased frailty, and increased risks of fractures and falls. In addition, spinal sarcopenia has been associated with lumbar spine disorders and osteoporosis, which renders making decisions on treatment modalities difficult. Patients with spinal sarcopenia typically exhibit lower cumulative survival, a higher risk of in-hospital complications, prolonged hospital stays, higher postoperative costs, and higher rates of blood transfusion after thoracolumbar spine surgery. Several studies have focused on the relationships between spinal sarcopenia, appendicular muscle mass, and bone-related problems-such as osteoporotic fractures and low bone mineral density-and malnutrition and vitamin D deficiency. Although several techniques are available for measuring sarcopenia, each of them has its advantages and shortcomings. For treating spinal sarcopenia, nutrition, physical therapy, and medication have been proven to be effective; regenerative therapeutic options seem to be promising owing to their repair and regeneration potential. Therefore, in this narrative review, we summarize the characteristics, detection methodologies, and treatment options for spinal sarcopenia, as well as its role in spinal disorders.

Three-Dimensional Printed Porous Titanium Screw with Bioactive Surface Modification for Bone-Tendon Healing: A Rabbit Animal Model.

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.

Removal of toluene vapor in the absence and presence of a quorum-sensing molecule in a biotrickling filter and microbial composition shift.

Toluene is highly toxic and mutagenic, and it is generally used as an industrial solvent. Thus, toluene removal from air is necessary. To solve the problem of reducing high toluene concentrations with a short gas retention time (GRT), a quorum-sensing molecule [N-(3-oxododecanoyl)-L-homoserine lactone] (OHL) was added to a biotrickling filter (BTF). In this study, a BTF was used to treat synthetic and natural waste gases containing toluene. An extensive analysis was performed to understand the removal efficiency, removal characteristics, and bacterial community of the BTF. The addition of 20 µM OHL to the BTF significantly improved toluene removal, and more than 99.2% toluene removal was achieved at a GRT of 0.5 min when natural waste gas containing toluene (590-1020 ppm or 2.21-3.83 g m-3) was introduced. The maximum inlet load for toluene was 337.9 g m-3 h-1. Moreover, the BTF exhibited satisfactory adaptability to shock loading and shutdown operations. Pseudomonadaceae (33.0%) and Comamonadaceae (26.3%) were predominant bacteria in the system after a 98-day operation. These bacteria were responsible for toluene degradation. The optimal moisture content and low pressure drop for system operations demonstrated that the BTF was energy and cost efficient. Therefore, processing through a BTF with OHL is a favorable technique for toluene treatment.

Decreased ω-6:ω-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury.

Ethanol (EtOH)-induced alterations in intestinal homeostasis lead to multi-system pathologies, including liver injury. ω-6 PUFAs exert pro-inflammatory activity, while ω-3 PUFAs promote anti-inflammatory activity that is mediated, in part, through specialized pro-resolving mediators [e.g., resolvin D1 (RvD1)]. We tested the hypothesis that a decrease in the ω-6:ω-3 PUFA ratio would attenuate EtOH-mediated alterations in the gut-liver axis. ω-3 FA desaturase-1 (fat-1) mice, which endogenously increase ω-3 PUFA levels, were protected against EtOH-mediated downregulation of intestinal tight junction proteins in organoid cultures and in vivo. EtOH- and lipopolysaccharide-induced expression of INF-γ, Il-6, and Cxcl1 was attenuated in fat-1 and WT RvD1-treated mice. RNA-seq of ileum tissue revealed upregulation of several genes involved in cell proliferation, stem cell renewal, and antimicrobial defense (including Alpi and Leap2) in fat-1 versus WT mice fed EtOH. fat-1 mice were also resistant to EtOH-mediated downregulation of genes important for xenobiotic/bile acid detoxification. Further, gut microbiome and plasma metabolomics revealed several changes in fat-1 versus WT mice that may contribute to a reduced inflammatory response. Finally, these data correlated with a significant reduction in liver injury. Our study suggests that ω-3 PUFA enrichment or treatment with resolvins can attenuate the disruption in intestinal homeostasis caused by EtOH consumption and systemic inflammation with a concomitant reduction in liver injury.