Lazertinib versus Platinum-Based Chemotherapy with Epidermal Growth Factor Receptor (EGFR)-Positive Non-Small-Cell Lung Cancer after Failing EGFR-Tyrosine Kinase Inhibitor: A Real-World External Comparator Study.

BACKGROUND: Lazertinib is a third-generation tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) that selectively inhibit common EGFR mutation and T790M mutation in non-small-cell lung cancer (NSCLC) patients. No previous studies have compared lazertinib to platinum-based chemotherapy. We have compared lazertinib with platinum-based chemotherapy in EGFR-mutated NSCLC patients after previous EGFR-TKI therapy. METHODS: We retrospectively compared 200 patients from LASER201, LASER301, and LASER-PMS studies to 334 patients who were treated with platinum-based chemotherapy after previous EGFR-TKI from the Samsung Medical Center. After propensity score matching (PSM), we selected 156 patients from each group. The primary outcome was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and time to treatment discontinuation (TTD) as secondary outcomes. RESULTS: The median follow-up of PFS was 15.61 months in the lazertinib group and 21.67 months in the external control group. The PFS was significantly longer in patients who were treated with lazertinib than those treated with platinum-based chemotherapy (10.97 months vs. 5.10 months; adjusted hazard ratio (HR) 0.40; 95% confidence interval (CI), 0.29-0.55; p < 0.01) after PSM. Lazertinib showed superior OS (32.23 months vs. 18.73 months; adjusted HR 0.45; 95% CI, 0.29-0.69; p < 0.001), ORR (64.1% vs. 47.4%), and TTD (11.66 months vs. 6.73 months; adjusted HR 0.54; 95% CI, 0.39-0.75; p < 0.001) compared to platinum-based chemotherapy. CONCLUSION: Based on this retrospective, external control study, lazertinib has demonstrated significantly better efficacy compared with platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies.

Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control.

Lazertinib is a recently developed third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors used for patients with advanced EGFR T790M-positive non-small-cell lung cancer. We evaluated the effectiveness of lazertinib compared with osimertinib using an external control. We obtained individual patient data for the lazertinib arm from the LASER201 trial and the osimertinib arm from registry data at the Samsung Medical Center. In total, 75 and 110 patients were included in the lazertinib and osimertinib groups, respectively. After propensity score matching, each group had 60 patients and all baseline characteristics were balanced. The median follow-up duration was 22.0 and 29.6 months in the lazertinib and osimertinib group, respectively. The objective response rate (ORR) were 76.7% and 86.7% for lazertinib and osimertinib, respectively (p = 0.08). The median progression-free survival (PFS) was 12.3 months (95% confidence interval [CI] 9.5-19.1) and 14.4 months (95% CI 11.8-18.1) for the lazertinib and osimertinib group, respectively (hazard ratio [HR] 0.97; 95% CI 0.64-1.45, p = 0.86). The median overall survival with lazertinib was not reached and that with osimertinib was 29.8 months (HR 0.44; 95% CI 0.25-0.77, p = 0.005). Our study suggests that lazertinib has an ORR and PFS comparable to those of osimertinib and has the potential for superior survival benefits.

Scaffolding fundamentals and recent advances in sustainable scaffolding techniques for cultured meat development.

In cultured meat (CM) production, Scaffolding plays an important role by aiding cell adhesion, growth, differentiation, and alignment. The existence of fibrous microstructure in connective and muscle tissues has attracted considerable interest in the realm of tissue engineering and triggered the interest of researchers to implement scaffolding techniques. A wide array of research efforts is ongoing in scaffolding technologies for achieving the real meat structure on the principality of biomedical research and to replace serum free CM production. Scaffolds made of animal-derived biomaterials are found efficient in replicating the extracellular matrix (ECM), thus focus should be paid to utilize animal byproducts for this purpose. Proper identification and utilization of plant-derived scaffolding biomaterial could be helpful to add diversified options in addition to animal derived sources and reduce in cost of CM production through scaffolds. Furthermore, techniques like electrospinning, modified electrospinning and 3D bioprinting should be focused on to create 3D porous scaffolds to mimic the ECM of the muscle tissue and form real meat-like structures. This review discusses recent advances in cutting edge scaffolding techniques and edible biomaterials related to structured CM production.

Comparative Biological Half-Life of Penthiopyrad and Tebufenpyrad in Angelica Leaves and Establishment of Pre-Harvest Residue Limits (PHRLs).

To prevent pesticides from exceeding maximum residue limits (MRLs) in crops during export and shipment, it is necessary to manage residue levels during the pre-harvest stages. Therefore, the Republic of Korea establishes pre-harvest residue limits (PHRLs) per crop and pesticide. This study was conducted to set PHRLs for penthiopyrad and tebufenpyrad in angelica leaves, where the exceedance rates of MRLs are expected to be high. The LOQ of the analytical method used was 0.01 mg/kg and it demonstrated good linearity, with a correlation coefficient of 0.999 or higher within the quantitation range of 0.005 to 0.5 mg/kg. The recovery and storage stability accuracy values were in the range of 94.5-111.1%, within the acceptable range (70-120%, RSD ≤ 20%). The matrix effect for both pesticides was in the medium-to-strong range, and it did not significantly impact the quantitative results as a matrix-matched calibration method was employed. Using the validated method, residue concentrations of penthiopyrad 20 (%) EC and tebufenpyrad 10 (%) EC were analyzed. Both pesticides exhibited a decreasing residue trend over time. In Fields 1-3 and their integrated results, the biological half-life was within 2.6-4.0 days for penthiopyrad and 3.0-4.2 days for tebufenpyrad. The minimum value of the regression coefficient in the dissipation curve regression equation was selected as the dissipation constant. The selected dissipation constants for penthiopyrad in Fields 1-3 and their integration were 0.1221, 0.2081, 0.2162, and 0.1960. For tebufenpyrad, the dissipation constants were 0.1451, 0.0960, 0.1725, and 0.1600, respectively. The dissipation constant was used to calculate PHRL per field. Following the principles of the PHRL proposal process, residue levels (%) on PHI dates relative to MRLs were calculated, and fields for proposing PHRLs were selected. For penthiopyrad, since the residue level (%) was less than 20%, the PHRL for Field 3 with the largest dissipation constant was proposed. For tebufenpyrad, as the residue level (%) exceeded 80%, the PHRL proposal could not established. It is deemed necessary to reassess the MRL and 'guidelines for safe use' for tebufenpyrad in angelica leaves.

Transcription factors BZR1 and PAP1 cooperate to promote anthocyanin biosynthesis in Arabidopsis shoots.

Anthocyanins play critical roles in protecting plant tissues against diverse stresses. The complicated regulatory networks induced by various environmental factors modulate the homeostatic level of anthocyanins. Here, we show that anthocyanin accumulation is induced by brassinosteroids (BRs) in Arabidopsis (Arabidopsis thaliana) shoots and shed light on the underlying regulatory mechanism. We observed that anthocyanin levels are altered considerably in BR-related mutants, and BRs induce anthocyanin accumulation by up-regulating the expression of anthocyanin biosynthetic genes. Our genetic analysis indicated that BRASSINAZOLE RESISTANT 1 (BZR1) and PRODUCTION OF ANTHOCYANIN PIGMENT 1 (PAP1) are essential for BR-induced anthocyanin accumulation. The BR-responsive transcription factor BZR1 directly binds to the PAP1 promoter, regulating its expression. In addition, we found that intense anthocyanin accumulation caused by the pap1-D dominant mutation is significantly reduced in BR mutants, implying that BR activity is required for PAP1 function after PAP1 transcription. Moreover, we demonstrated that BZR1 physically interacts with PAP1 to cooperatively regulate the expression of PAP1 target genes, such as TRANSPARENT TESTA 8 (TT8), DIHYDROFLAVONOL 4-REDUCTASE (DFR), and LEUKOANTHOCYANIDIN DIOXYGENASE (LDOX). Our findings indicate that BZR1 functions as an integral component of the PAP1-containing transcription factor complex, contributing to increased anthocyanin biosynthesis. Notably, we also show that functional interaction of BZR1 with PAP1 is required for anthocyanin accumulation induced by low nitrogen stress. Taken together, our results demonstrate that BR-regulated BZR1 promotes anthocyanin biosynthesis through cooperative interaction with PAP1 of the MBW complex.

Thermal Runaway Mechanism in Ni-Rich Cathode Full Cells of Lithium-Ion Batteries: The Role of Multidirectional Crosstalk.

Crosstalk, the exchange of chemical species between battery electrodes, significantly accelerates thermal runaway (TR) of lithium-ion batteries. To date, the understanding of their main mechanisms has centered on single-directional crosstalk of oxygen (O2) gas from the cathode to the anode, underestimating the exothermic reactions during TR. However, the role of multidirectional crosstalk in steering additional exothermic reactions is yet to be elucidated due to the difficulties of correlative in situ analyses of full cells. Herein, the way in which such crosstalk triggers self-amplifying feedback is elucidated that dramatically exacerbates TR within enclosed full cells, by employing synchrotron-based high-temperature X-ray diffraction, mass spectrometry, and calorimetry. These findings reveal that ethylene (C2H4) gas generated at the anode promotes O2 evolution at the cathode. This O2 then returns to the anode, further promoting additional C2H4 formation and creating a self-amplifying loop, thereby intensifying TR. Furthermore, CO2, traditionally viewed as an extinguishing gas, engages in the crosstalk by interacting with lithium at the anode to form Li2CO3, thereby accelerating TR beyond prior expectations. These insights have led to develop an anode coating that impedes the formation of C2H4 and O2, to effectively mitigate TR.

Single-Cell Analysis Uncovers Striking Cellular Heterogeneity of Lung-Infiltrating Regulatory T Cells during Eosinophilic versus Neutrophilic Allergic Airway Inflammation.

Allergic airway inflammation results from uncontrolled immune responses to environmental Ags. Although it is well established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types such as eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the mechanisms responsible for such pathogenesis remain elusive. Foxp3+ regulatory T cells (Tregs) are essential immune regulators during chronic inflammation, including allergic airway inflammation. Emerging evidence suggests that Tregs infiltrating inflamed tissues exhibit distinct phenotypes dependent on the specific tissue sites and can display heterogeneity and tissue residency. Whether diverse allergic airway inflammatory responses influence infiltrating Treg heterogeneity or Treg lung residency has not been explored. We employed an unbiased single-cell RNA sequencing approach to investigate lung-infiltrating Tregs in models of eosinophilic and neutrophilic airway inflammation. We found that lung-infiltrating Tregs are highly heterogeneous, and that Tregs displaying lung-resident phenotypes are significantly different depending on the types of inflammation. Treg expression of ST2, a receptor for alarmin IL-33, was predominantly associated with eosinophilic inflammation and tissue residency. Nevertheless, Treg-specific ST2 deficiency did not affect the development of eosinophilic allergic inflammation or the generation of lung-resident Tregs. These results uncover a stark heterogeneity among Tregs infiltrating the lungs during allergic airway inflammation. The results indicate that varying types of inflammation may give rise to phenotypically distinct lung-resident Tregs, underscoring a (to our knowledge) novel mechanism by which inflammatory cues may shape the composition of infiltrating Tregs, allowing them to regulate inflammatory responses through tissue-adapted mechanisms.

An Ultrasoft and Flexible PDMS-Based Balloon-Type Implantable Device for Controlled Drug Delivery.

Non-biodegradable implants have undergone extensive investigation as drug delivery devices to enable advanced healthcare toward personalized medicine. However, fibroblast encapsulation is one of the major challenges in all non-biodegradable implants, besides other challenges such as high initial burst, risk of membrane rupture, high onset time, non-conformal contact with tissues, and tissue damage. To tackle such challenges, we propose a novel ultrasoft and flexible balloon-type drug delivery device for unidirectional and long-term controlled release. The ultrasoft balloon-type device (USBD) was fabricated by using selective bonding between 2 polydimethylsiloxane (PDMS) membranes and injecting a fluid into the non-bonded area between them. The balloon acted as a reservoir containing a liquid drug, and at the same time, the membrane of the balloon itself acted as the pathway for release based on diffusion. The release was modulated by tuning the thickness and composition of the PDMS membrane. Regardless of the thickness and composition, all devices exhibited zero-order release behavior. The longest zero-order release and nearly zero-order release were achieved for 30 days and 58 days at a release rate of 1.16 µg/day and 1.68 µg/day, respectively. In vivo evaluation was performed for 35 days in living rats, where the USBD maintained zero-order and nearly zero-order release for 28 days and 35 days, respectively. Thanks to the employment of ultrasoft and flexible membranes and device design, the USBD could achieve minimal tissue damage and foreign body responses. It is expected that the proposed device may provide a novel approach for long-term drug delivery with new therapeutic modalities.

Comparative analysis of the efficacy of vaccines using structural protein subunits of the severe fever with thrombocytopenia syndrome virus.

The severe fever with thrombocytopenia syndrome virus (SFTSV) represents a significant emerging health threat as a tick-borne pathogen that causes SFTS, with mortality rates ranging between 10 and 30%. Despite the considerable risk presented by SFTSV, an effective vaccine has yet to be developed. Our study assessed the efficacy of recombinant protein vaccines, focusing on the purified nucleocapsid protein (NP) and surface glycoproteins (Gn and Gc), against SFTSV in both singular and combined formulations. Individual vaccinations with NP or Gn subunits yielded partial protection in type I interferon receptor-knockout (IFNAR-KO) mice, with survival rates of 66.7 and 16.7%, respectively, whereas Gc vaccination did not confer significant protection, resulting in 100% mortality similar to that of the unvaccinated control group. Notably, NP vaccination substantially enhanced antigen-specific T cell responses, and Gc vaccination exhibited strong neutralizing activity against SFTSV. Among the combined recombinant protein formulations (Gn + NP, Gc + NP, and Gn + Gc + NP) tested, the Gc + NP combination provided the highest survival rate (85.7%) following challenge with a lethal dose of SFTSV, highlighting its potential as a vaccine candidate. Longitudinal studies showed that antibody levels in both wild type C57BL/6 and IFNAR-KO mice peaked between 2 and 3 months post-vaccination and declined over time. A notable decrease in NP-specific CD8+ T cell responses was observed 6 months post-vaccination in C57BL/6 mice, while NP-specific CD4+ T cell responses persisted up to 12 months. By 12 months post-vaccination, all IFNAR-KO mice vaccinated with single subunit antigens succumbed to the virus, suggesting that effective protection against SFTS may rely on antibody responses to subunit antigens and/or CD8+ T cell activity. These findings underscore the necessity of an optimized SFTS vaccine that combines protective antigens with an adjuvant system to ensure durable humoral and cellular immunity.

Downloading appetite? Investigating the role of parasocial relationship with favorite social media food influencer in followers' disordered eating behaviors.

PURPOSE: Although a number of investigations have been carried out on the marketing outcomes of parasocial relationships (PSR) with food influencers on social media, little attention has been paid to the potential contribution of these one-sided emotional bonds to followers' eating attitudes and habits. Drawing on the Parasocial Theory, the role of parasocial attachment with food influencers was investigated in predicting eating disorders, food addiction, and grazing. To increase the accuracy of PSR measurement, a brief self-report scale was developed to gauge social media users' feelings of mutual awareness, attention, and adjustment with their favorite food influencer at a distance through social media. METHODS: Participants were a convenience sample of 405 Iranian social media users (231women; Mage = 28.16, SDage = 9.40), who followed a favorite food influencer on social media. RESULTS: The 8-item Parasocial Relationship with Favorite Food Influencer Scale (PSRFFIS) revealed a unidimensional structure with excellent content and construct validity and internal consistency. Regarding gender differences, men showed stronger parasocial attachment to their favorite food influencers. Adjusting age, gender, and subjective social status as control variables, PSR with favorite food influencers partially contributed to the explanation of eating disorder symptom severity, food addiction, and grazing. CONCLUSION: These findings show that PSR with favorite food influencers appears to be associated with followers' craving for food, which, in turn, may contribute to maladaptive eating habits. This highlights media-related factors, such as PSR with food influencers, as potential drivers of dysfunctional eating habits in the digital age, particularly in countries like Iran where disordered eating is prevalent. LEVEL OF EVIDENCE: Level V-based on cross-sectional data (correlational study; scale development).

KoCVAM-led development of phototoxicity alternative test method using reconstructed human epidermis model (KeraSkin™).

Phototoxicity is an acute toxic reaction induced by topical skin exposure to photoreactive chemicals followed by exposure to environmental light and thus chemicals that absorb UV are recommended to be evaluated for phototoxic potential. There are currently three internationally harmonized alternative test methods for phototoxicity. One of them is the in vitro Phototoxicity: RhE Phototoxicity test method (OECD TG498). Korean center for the Validation of Alternative Methods (KoCVAM) developed an in vitro phototoxicity test method using a KeraSkin™ reconstructed human epidermis model (KeraSkin™ Phototoxicity Assay) as a 'me-too' test method of OECD TG498. For the development and optimization of KeraSkin™ Phototoxicity Assay, the following test chemicals were used: 6 proficiency chemicals in OECD TG498 (3 phototoxic and 3 non-phototoxic), 6 reference chemicals in OECD Performance Standard No. 356 (excluding the proficiency test chemicals, 3 phototoxic and 3 non-phototoxic) and 13 additional chemicals (7 phototoxic and 6 non-phototoxic). Based on the test results generated from the test chemicals above, the overall predictive capacity of KeraSkin™ Phototoxicity Assay was calculated. In particular, the assay exhibited 100 % accuracy, 100 % sensitivity, and 100 % specificity. Therefore, it fulfills the requirements to be included as a 'me-too' test method in OECD TG498.

Social media-related nightmare - a potential explanation for poor sleep quality and low affective well-being in the social media era?

Research has posited that social media use during the day may be reflected in nighttime dreams. Nevertheless, no prior studies have explored frightening, unpleasant dreams arising from social media use. This study introduces the construct of the social media-related nightmare by (a) developing and validating a scale capturing negative-valenced dreams with themes of helplessness, loss of control, inhibition, victimization, and making mistakes in social media, and (b) examining relationships between social media use, social media-related nightmares, sleep quality, and affective well-being. A convenience sample of 595 Iranian adult social media users (Mage = 27.45, SDage = 11.42) reported on social media-related nightmare, social media use integration, anxiety, peace of mind, sleep quality, and nightmare distress. The Social Media-Related Nightmare Scale (SMNS) demonstrated a unidimensional structure with sound psychometric properties. The most common nightmares involved the inability to log in to social media and the disruption of relationships with other users. Social media use intensity predicted frequency of social media-related nightmares. These nightmares were correlated with increased anxiety, lower peace of mind, poor sleep quality, and nightmare distress. Importantly, social media-related nightmares mediated the relationship between social media use intensity and low affective well-being (i.e., anxiety and peace of mind), poor sleeping, and nightmare distress. The findings suggest that social media-related nightmares could be a potential pathway through which social media engagement may lead to affective distress and sleep difficulties.

Rise in broadly cross-reactive adaptive immunity against human ß-coronaviruses in MERS-recovered patients during the COVID-19 pandemic.

To develop a universal coronavirus (CoV) vaccine, long-term immunity against multiple CoVs, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, Middle East respiratory syndrome (MERS)-CoV, and future CoV strains, is crucial. Following the 2015 Korean MERS outbreak, we conducted a long-term follow-up study and found that although neutralizing antibodies and memory T cells against MERS-CoV declined over 5 years, some recovered patients exhibited increased antibody levels during the COVID-19 pandemic. This likely resulted from cross-reactive immunity induced by SARS-CoV-2 vaccines or infections. A significant correlation in antibody responses across various CoVs indicates shared immunogenic epitopes. Two epitopes-the spike protein's stem helix and intracellular domain-were highly immunogenic after MERS-CoV infection and after SARS-CoV-2 vaccination or infection. In addition, memory T cell responses, especially polyfunctional CD4+ T cells, were enhanced during the pandemic, correlating significantly with MERS-CoV spike-specific antibodies and neutralizing activity. Therefore, incorporating these cross-reactive and immunogenic epitopes into pan-CoV vaccine formulations may facilitate effective vaccine development.

Focal stimulation of retinal ganglion cells using subretinal 3D microelectrodes with peripheral electrodes of opposite current.

Subretinal prostheses have been developed to stimulate survived retinal ganglion cells (RGCs), indirectly following the physiological visual pathways. However, current spreading from the prosthesis electrode causes the activation of unintended RGCs, thereby limiting the spatial resolution of artificial vision. This study proposes a strategy for focal stimulation of RGCs using a subretinal electrode array, in which six hexagonally arranged peripheral electrodes surround a stimulating electrode. RGCs in an in-vitro condition were subretinally stimulated using a fabricated electrode array coated with iridium oxide, following the three different stimulation configurations (with no peripheral, six electrodes of opposite current, and six ground). In-vitro experiments showed that the stimulation with six electrodes of opposite current was most effective in controlling RGC responses with a high spatial resolution. The results suggest that the effective utilization of return electrodes, such as by applying an opposite current to them, could help reduce current spreading beyond the local area targeted for stimulation and elicit RGC responses only in the vicinity of the stimulating electrode. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00342-3.

Trends in Hybrid Cultured Meat Manufacturing Technology to Improve Sensory Characteristics.

The projected growth of global meat production over the next decade is attributed to rising income levels and population expansion. One potentially more pragmatic approach to mitigating the adverse externalities associated with meat production involves implementing alterations to the production process, such as transitioning to cultured meat, hybrid cultured meat, and meat alternatives. Cultured meat (CM) is derived from animal stem cells and undergoes a growth and division process that closely resembles the natural in vivo cellular development. CM is emerging as a widely embraced substitute for traditional protein sources, with the potential to alleviate the future strain on animal-derived meat production. To date, the primary emphasis of cultured meat research and production has predominantly been around the ecological advantages and ethical considerations pertaining to animal welfare. However, there exists substantial study potential in exploring consumer preferences with respect to the texture, color, cuts, and sustainable methodologies associated with cultured meat. The potential augmentation of cultured meat's acceptance could be facilitated through the advancement of a wider range of cuts to mimic real muscle fibers. This review examines the prospective commercial trends of hybrid cultured meat. Subsequently, the present state of research pertaining to the advancement of scaffolding, coloration, and muscle fiber development in hybrid cultured meat, encompassing plant-based alternatives designed to emulate authentic meat, has been deliberated. However, this discussion highlights the obstacles that have arisen in current procedures and proposes future research directions for the development of sustainable cultured meat and meat alternatives, such as plant-based meat production.

Comparative analysis of BZR1/BES1 family transcription factors in Arabidopsis.

Brassinazole Resistant 1 (BZR1) and bri1 EMS Suppressor 1 (BES1) are key transcription factors that mediate brassinosteroid (BR)-responsive gene expression in Arabidopsis. The BZR1/BES1 family is composed of BZR1, BES1, and four BES1/BZR1 homologs (BEH1-BEH4). However, little is known about whether BEHs are regulated by BR signaling in the same way as BZR1 and BES1. We comparatively analyzed the functional characteristics of six BZR1/BES1 family members and their regulatory mechanisms in BR signaling using genetic and biochemical analyses. We also compared their subcellular localizations regulated by the phosphorylation status, interaction with GSK3-like kinases, and heterodimeric combination. We found that all BZR1/BES1 family members restored the phenotypic defects of bri1-5 by their overexpression. Unexpectedly, BEH2-overexpressing plants showed the most distinct phenotype with enhanced BR responses. RNA-Seq analysis indicated that overexpression of both BZR1 and BEH2 regulates BR-responsive gene expression, but BEH2 has a much greater proportion of BR-independent gene expression than BZR1. Unlike BZR1 and BES1, the BR-regulated subcellular translocation of the four BEHs was not tightly correlated with their phosphorylation status. Notably, BEH1 and BEH2 are predominantly localized in the nucleus, which induces the nuclear accumulation of other BZR1/BES1 family proteins through heterodimerization. Altogether, our comparative analyses suggest that BEH1 and BEH2 play an important role in the functional interaction between BZR1/BES1 family transcription factors.

High-Performing and Capacitive-Matched Triboelectric Implants Driven by Ultrasound.

In implantable bioelectronics, which aim for semipermanent use of devices, biosafe energy sources and packaging materials to protect devices are essential elements. However, research so far has been conducted in a direction where they cannot coexist. Here, the development of capacitance-matched triboelectric implants driven is reported by ultrasound under 500 mW cm-2 safe intensity and realize a battery-free, miniatured, and wireless neurostimulator with full titanium (Ti) packaging. The triboelectric implant with high dielectric composite, which has ultralow output impedance, can efficiently deliver sufficient power to generate the stimulation pulse without an energy-storing battery, despite ultrasound attenuation due to the Ti, and has the highest energy transmission efficiency among those reported so far. In vivo study using a rat model demonstrated that the proposed device system is an effective solution for relieving urinary symptoms. These achievements provide a significant step toward permanently implantable devices for controlling human organs and treating various diseases.

Commensal bacteria promote type I interferon signaling to maintain immune tolerance in mice.

Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling.

Retrospective evaluation of prognosis and survival with various immunosuppressants in 82 dogs diagnosed with meningoencephalitis of unknown etiology (2010-2021).

BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.

Supplementation with fibroblast growth factor 7 during in vitro maturation of porcine cumulus-oocyte complexes improves oocyte maturation and early embryonic development.

In vitro generation of porcine embryos is an indispensable method in the realms of both agriculture and biomedicine. Nonetheless, the extant procedures encounter substantial obstacles pertaining to both the caliber and efficacy of the produced embryos, necessitating extensive research to in vitro maturation (IVM), the seminal commencement phase. One potentially fruitful approach may lie in refining the media and supplements composition utilized for oocyte maturation. Fibroblast growth factor-7 (FGF7), alternatively termed keratinocyte growth factor, is a theca-derived cytokine integral to folliculogenesis. This study aimed to examine the ramifications of supplementing FGF7 during the IVM phase. To determine the FGF7 location and its receptor in porcine ovaries, immunohistochemistry was executed based on follicle size categories (1-2, 3-6, and 7-9 mm). Regardless of follicle size, it was determined that FGF7 was expressed in theca and granulosa cells (GCs), whereas the FGF7 receptor was only expressed in the GCs of the larger follicles. During the IVM process, the maturation medium was supplied with various concentrations of FGF7, aiming to mature porcine cumulus-oocyte complexes (COCs). The data indicated a significant augmentation in the nuclear maturation rate only within the group treated with 10 ng/mL of FGF7 (p < 0.05). Post-IVM, the oocytes diameter exhibited a significant expansion in all groups that received FGF7 supplementation (p < 0.05). Additionally, all FGF7-supplemented groups exhibited a substantial elevation in intracellular glutathione levels, coupled with a noticeable reduction in reactive oxygen species levels (p < 0.05). With respect to gene expressions related to apoptosis, FGF7 treatment elicited a downregulation of pro-apoptotic genes and an upregulation of anti-apoptotic genes. The expression of genes associated with antioxidants underwent a significant enhancement (p < 0.05). In terms of the FGF7 signaling pathway-associated genes, there was a significant elevation in the mRNA expression of ERK1, ERK2, c-kit, and KITLG (p < 0.05). Remarkably, the group of 10 ng/mL of FGF7 demonstrated an appreciable uptick in the blastocyst formation rate during embryonic development post-parthenogenetic activation (p < 0.05). In conclusion, the FGF7 supplementation during IVM substantially augments the quality of matured oocytes and facilitates the subsequent development of parthenogenetically activated embryos. These results offer fresh perspectives on improved maturation and following in vitro evolution of porcine oocytes.