Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections.

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003-2007) to 39.7% (2018-2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum ß-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

Transcriptional regulation of Tfh dynamics and the formation of immunological synapses.

Inside germinal centers (GCs), antigen-specific B cells rely on precise interactions with immune cells and strategic localization between the dark and light zones to clonally expand, undergo affinity maturation, and differentiate into long-lived plasma cells or memory B cells. Follicular helper T (Tfh) cells, the key gatekeepers of GC-dependent humoral immunity, exhibit remarkable dynamic positioning within secondary lymphoid tissues and rely on intercellular interactions with antigen-presenting cells (APCs) during their differentiation and execution of B-cell-facilitating functions within GCs. In this review, we briefly cover the transcriptional regulation of Tfh cell differentiation and function and explore the molecular mechanisms governing Tfh cell motility, their interactions with B cells within GCs, and the impact of their dynamic behavior on humoral responses.

Patrinia villosa (Thunb.) Juss alleviates CCL4-induced acute liver injury by restoring bile acid levels and inhibiting apoptosis/autophagy.

Background: Patrinia villosa (Thunb.) Juss is one of the plant resources of the famous traditional Chinese medicine "Bai jiang cao (herba patriniae)," and it is considered to function at the liver meridian, thereby treating diseases of the liver as demonstrated by the traditional theory of TCM. Unfortunately, the therapeutic mechanism of the whole plant of PV is so far unknown. Method: UPLC QTOF-MS/MS was used to analyze the profile of PV. Male Sprague-Dawley rats were categorized into five groups, and PV groups (125 and 375 mg/kg) were administered by oral gavage for seven consecutive days. The model of liver injury was induced by intraperitoneal injection of 40% CCl4 oil solution. H&E staining was performed for histological evaluation. The ELISA method was used to assess the serum level of ALT, AST, and T-BIL. Serum and liver bile acid (BA) profiling was analyzed by LC-MS/MS. TUNEL-stained liver sections were used to monitor apoptosis caused by CCl4. HepG2 cells were used to detect autophagy caused by CCl4. Results: A total of 16 compounds were identified from the 70% methanol extract of PV. PV (125 and 375 mg/kg) could reverse the ectopic overexpression of AST, ALT, and T-BIL caused by CCl4 administration. H&E staining indicated that PV (125 and 375 mg/kg) could reduce the infiltration of inflammatory cells and restore liver tissue and hepatocyte structures. Six bile acids, including DCA, HDCA, GCA, TCA, TCDCA, and TUDCA, were significantly altered both in the serum and liver tissue after CCl4 administration, and the level of all these six bile acids was restored by PV treatment. Moreover, PV inhibited apoptosis caused by CCl4 stimulation in liver tissue and suppressed autophagy in HepG2 cells treated with CCl4. Conclusion: The results in this paper for the first time reveal the alteration of the bile acid profile in CCl4-induced liver injury and demonstrate that inhibiting apoptosis and autophagy was involved in P. villosa-elicited liver protection, providing a scientific basis for the clinical utilization of P. villosa as a natural hepatic protective agent.

Unraveling motives: identifying the impact of university attendance motives on learning behaviors among dental students.

PURPOSE: Students report various motives for attending university (MAU) grouped under five categories, namely, personal-intellectual development (PER), humanitarian (HUM), careerist-materialist (CAR), expectation-driven (EXP), and uncertain motives. Although the literature demonstrates that these motives exert an influence on learning and achievement, relatively less attention is given to this issue in the context of dental students. This study aimed to examine the relationship among the mindsets, MAU, academic engagement (AE), and DAL of dental students and to test the mediating effect of AE on the relationship between MAU and deep approach to learning (DAL). METHODS: The study recruited 226 dental students at various levels of the curriculum, who responded to four questionnaires for measuring MAU, DAL, mindsets, and AE. The study employed structural equation modeling to analyze the mediation effects of AE on the relationship between MAU and DAL and to determine the influence of mindsets on MAU. RESULTS: This model reveals the significant relationships of a growth mindset with CAR, PER, and HUM. Moreover, the study finds that a fixed mindset was associated with CAR, EXP, and uncertain motives. Furthermore, AE only fully mediated the significant positive relationship between PER and DAL, whereas CAR negatively predicted DAL without a mediator. CONCLUSIONS: These findings suggest that administering the inventories in a dental school setting can facilitate a more comprehensive understanding of students' mindsets toward learning and effective processes related to learning. This understanding can inform instructors' pedagogical practices, enabling them to provide more effective guidance to students navigating the complexities of academic coursework.

From lab to wearables: Innovations in multifunctional hydrogel chemistry for next-generation bioelectronic devices.

Functional hydrogels have emerged as foundational materials in diagnostics, therapy, and wearable devices, owing to their high stretchability, flexibility, sensing, and outstanding biocompatibility. Their significance stems from their resemblance to biological tissue and their exceptional versatility in electrical, mechanical, and biofunctional engineering, positioning themselves as a bridge between living organisms and electronic systems, paving the way for the development of highly compatible, efficient, and stable interfaces. These multifaceted capability revolutionizes the essence of hydrogel-based wearable devices, distinguishing them from conventional biomedical devices in real-world practical applications. In this comprehensive review, we first discuss the fundamental chemistry of hydrogels, elucidating their distinct properties and functionalities. Subsequently, we examine the applications of these bioelectronics within the human body, unveiling their transformative potential in diagnostics, therapy, and human-machine interfaces (HMI) in real wearable bioelectronics. This exploration serves as a scientific compass for researchers navigating the interdisciplinary landscape of chemistry, materials science, and bioelectronics.

PEDOT:PSS-Based Prolonged Long-Term Decay Synaptic OECT with Proton Permeable Material, Nafion.

Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), a conductive polymer, has gained popularity as the channel layer in organic electrochemical transistors (OECTs) due to its high conductivity and straightforward processing. However, difficulties arise in controlling its conductivity through gate voltage, presenting a challenge. To address this issue, we employ aromatic amidine base, diazabicyclo[4.3.0]non-5-ene (DBN), to stabilize the doping state of the PEDOT chain through a reliable chemical de-doping process. Furthermore, the addition of the proton-penetrable material Nafion to the PEDOT:PSS channel layer induces phase separation between the substances. By utilizing a solution containing both PEDOT:PSS and Nafion as the channel layer of OECTs, we enhance the efficiency of ion movement into the channel from the electrolyte, resulting in improved OECT performance. The inclusion of Nafion in the OECTs' channel layer modifies ion movement dynamics, allowing for the adjustment of synaptic properties such as pulse-paired facilitation (PPF), memory level, short-term plasticity (STP), and long-term plasticity (LTP). This research aims to introduce new possibilities in the field of neuromorphic computing and contribute to biomimetic technology through the enhancement of electronic component performance This article is protected by copyright. All rights reserved.

Micropropagation and Shoot Tip Cryopreservation of 'Sunny Gold' Freesia.

Cryopreservation is a promising method for the long-term preservation of plant germplasm, especially for vegetatively propagated species like freesias. In this study, we investigate streamlining the cryopreservation process for 'Sunny Gold' Freesia, starting from effective in vitro initiation and proliferation using various plant growth regulator combinations. We also assess the impact of subculture on regrowth rates after cryopreservation. The shoot tips were successfully initiated in vitro after sterilization. The shoots were multiplied an average of three times in media containing N6-benzyladenine and kinetin. The regrowth rates of non-cryopreserved shoot tips excised from different subculture cycles did not differ significantly, with rates of 44% observed for plants from more than five subcultures and 47% for those from three subcultures. However, only the shoot tips excised from cultures subjected to three subculture cycles were able to recover after cryopreservation, with a regrowth rate of 31%. Our findings lay the groundwork for the development of an efficient cryopreservation protocol for freesias in the future.

Biomarkers of Neurodegeneration and Alzheimer's Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study.

Adult-onset diabetes increases one's risk of neurodegenerative disease including Alzheimer's disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aß40, Aß42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aß40, Aß42, and GFAP, and higher pTau181 compared to controls (p < 0.05), a pattern persisting into adulthood (p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM (p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases.

LTA and PGN from Bacillus siamensis can alleviate soybean meal-induced enteritis and microbiota dysbiosis in Lateolabrax maculatus.

An eight-week feeding trial was designed to assess which component of commensal Bacillus siamensis LF4 can mitigate SBM-induced enteritis and microbiota dysbiosis in spotted seabass (Lateolabrax maculatus) based on TLRs-MAPKs/NF-кB signaling pathways. Fish continuously fed low SBM (containing 16 % SBM) and high SBM (containing 40 % SBM) diets were used as positive (FM group) and negative (SBM group) control, respectively. After feeding high SBM diet for 28 days, fish were supplemented with B. siamensis LF4-derived whole cell wall (CW), cell wall protein (CWP), lipoteichoic acid (LTA) or peptidoglycan (PGN) until 56 days. The results showed that a high inclusion of SBM in the diet caused enteritis, characterized with significantly (P < 0.05) decreased muscular thickness, villus height, villus width, atrophied and loosely arranged microvillus. Moreover, high SBM inclusion induced an up-regulation of pro-inflammatory cytokines and a down-regulation of occludin, E-cadherin, anti-inflammatory cytokines, apoptosis related genes and antimicrobial peptides. However, dietary supplementation with CW, LTA, and PGN of B. siamensis LF4 could effectively alleviate enteritis caused by a high level of dietary SBM. Additionally, CWP and PGN administration increased beneficial Cetobacterium and decreased pathogenic Plesiomonas and Brevinema, while dietary LTA decreased Plesiomonas and Brevinema, suggesting that CWP, LTA and PGN positively modulated intestinal microbiota in spotted seabass. Furthermore, CW, LTA, and PGN application significantly stimulated TLR2, TLR5 and MyD88 expressions, and inhibited the downstream p38 and NF-κB signaling. Taken together, these results suggest that LTA and PGN from B. siamensis LF4 could alleviate soybean meal-induced enteritis and microbiota dysbiosis in L. maculatus, and p38 MAPK/NF-κB pathways might be involved in those processes.

Synthetic ShK-like Peptide from the Jellyfish Nemopilema nomurai Has Human Voltage-Gated Potassium-Channel-Blocking Activity.

We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues (3Asp, 25Lys, and 34Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3Glu, 25Arg, and 34Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts.

Age-Related Conservation in Plant-Soil Feedback Accompanied by Ectomycorrhizal Domination in Temperate Forests in Northeast China.

This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant-soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant-soil traits by comparing younger (~120 years) and older (~250 years) temperate forest stands in Northeast China. The results revealed increases in the EcM fungal richness and abundance with forest aging, paralleled by plant-soil feedback shifting from explorative to conservative nutrient use strategies. In the younger stands, Tomentella species were prevalent and showed positive correlations with nutrient availability in both the soil and leaves, alongside rapid increases in woody productivity. However, the older stands were marked by the dominance of the genera Inocybe, Hymenogaster, and Otidea which were significantly and positively correlated with soil nutrient contents and plant structural attributes such as the community-weighted mean height and standing biomass. Notably, the ratios of longer-to-shorter distance EcM fungal exploration types tended to decrease along with forest aging. Our findings underscore the integral role of EcM fungi in the aging processes of temperate forests, highlighting the EcM symbiont-mediated mechanisms adapting to nutrient scarcity and promoting sustainability in plant-soil consortia.

Commensal Bacillus pumilus SE5-Derived Peptidoglycan and Lipoteichoic Acid Showed Synergistic Effects in Improving Growth, Immunity, and Intestinal Health of Grouper (Epinephelus coioides).

Commensal-derived peptidoglycan (PG) or lipoteichoic acid (LTA) can improve the growth, immunity, and intestinal health of fish, but it is not clear whether the two components have synergistic effects. To clarify this, grouper (Epinephelus coioides) was fed basal diet (CG) or diets containing 1.0 × 108 CFU/g heat-inactivated SE5 (HIB), PG (21.30 mg/kg), LTA (6.70 mg/kg), mixture (PL1) of PG (10.65 mg/kg) and LTA (3.35 mg/kg), and mixture (PL2) of PG (21.30 mg/kg) and LTA (6.70 mg/kg). Improved growth performance and feed utilization were observed in groups PG, LTA, PL1, and PL2, and the optimum growth performance was recorded in group PL1. Furthermore, improved serum alkaline phosphatase (AKP) activity and immunoglobulin M (IgM) and complement C3 (C3) contents were observed in all treatments, and the AKP activity in group PL1 was significantly superior to that of groups PG and LTA. Although PG and LTA alone or in combination exert comparable effects on intestinal microbiota and physical structure, obviously enhanced intestinal protease activity was observed in group PL1. The combined efficacy of PL1 could further potentiate the immune response by modulating the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and upregulating the expression of antimicrobial peptides (epinecidin-1, hepcidin-1, and ß-defensin) as well as IgM. At the same time, group PL1 could further mitigate intestinal inflammation by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory cytokines. In conclusion, probiotic B. pumilus SE5-derived PG and LTA mixture (10.65 mg/kg PG and 3.35 mg/kg LTA) exhibits better potential for improving the growth performance, intestinal health, and immune function compared to another mixture (21.30 mg/kg PG and 6.70 mg/kg LTA) and PG or LTA alone in grouper.

The Effect of Brief Warming during Induction of General Anesthesia and Warmed Intravenous Fluid on Intraoperative Hypothermia in Patients Undergoing Urologic Surgery.

Background and Objectives: Transurethral urologic surgeries frequently lead to hypothermia due to bladder irrigation. Prewarming in the preoperative holding area can reduce the risk of hypothermia but disrupts surgical workflow, preventing it from being of practical use. This study explored whether early intraoperative warming during induction of anesthesia, known as peri-induction warming, using a forced-air warming device combined with warmed intravenous fluid could prevent intraoperative hypothermia. Materials and Methods: Fifty patients scheduled for transurethral resection of the bladder (TURB) or prostate (TURP) were enrolled and were randomly allocated to either the peri-induction warming or control group. The peri-induction warming group underwent whole-body warming during anesthesia induction using a forced-air warming device and was administered warmed intravenous fluid during surgery. In contrast, the control group was covered with a cotton blanket during anesthesia induction and received room-temperature intravenous fluid during surgery. Core temperature was measured upon entrance to the operating room (T0), immediately after induction of anesthesia (T1), and in 10 min intervals until the end of the operation (Tend). The incidence of intraoperative hypothermia, change in core temperature (T0-Tend), core temperature drop rate (T0-Tend/[duration of anesthesia]), postoperative shivering, and postoperative thermal comfort were assessed. Results: The incidence of intraoperative hypothermia did not differ significantly between the two groups. However, the peri-induction warming group exhibited significantly less change in core temperature (0.61 ± 0.3 °C vs. 0.93 ± 0.4 °C, p = 0.002) and a slower core temperature drop rate (0.009 ± 0.005 °C/min vs. 0.013 ± 0.004 °C/min, p = 0.013) than the control group. The peri-induction warming group also reported higher thermal comfort scores (p = 0.041) and less need for postoperative warming (p = 0.034) compared to the control group. Conclusions: Brief peri-induction warming combined with warmed intravenous fluid was insufficient to prevent intraoperative hypothermia in patients undergoing urologic surgery. However, it improved patient thermal comfort and mitigated the absolute amount and rate of temperature drop.

Administration of Gas6 attenuates lung fibrosis via inhibition of the epithelial-mesenchymal transition and fibroblast activation.

The epithelial-mesenchymal transition (EMT) and fibroblast activation are major events in idiopathic pulmonary fibrosis pathogenesis. Here, we investigated whether growth arrest-specific protein 6 (Gas6) plays a protective role in lung fibrosis via suppression of the EMT and fibroblast activation. rGas6 administration inhibited the EMT in isolated mouse ATII cells 14 days post-BLM treatment based on morphologic cellular alterations, changes in mRNA and protein expression profiles of EMT markers, and induction of EMT-activating transcription factors. BLM-induced increases in gene expression of fibroblast activation-related markers and the invasive capacity of primary lung fibroblasts in primary lung fibroblasts were reversed by rGas6 administration. Furthermore, the hydroxyproline content and collagen accumulation in interstitial areas with damaged alveolar structures in lung tissue were reduced by rGas6 administration. Targeting Gas6/Axl signaling events with specific inhibitors of Axl (BGB324), COX-2 (NS-398), EP1/EP2 receptor (AH-6809), or PGD2 DP2 receptor (BAY-u3405) reversed the inhibitory effects of rGas6 on EMT and fibroblast activation. Finally, we confirmed the antifibrotic effects of Gas6 using Gas6-/- mice. Therefore, Gas6/Axl signaling events play a potential role in inhibition of EMT process and fibroblast activation via COX-2-derived PGE2 and PGD2 production, ultimately preventing the development of pulmonary fibrosis.

Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.

RATIONALE & OBJECTIVE: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.8 [22.7-30.4] kg/m2; estimated glomerular filtration rate [eGFR, 2021 CKD-EPI creatinine], 103±18mL/min/1.73m2; height-adjusted total kidney volume [HTKV], 731±370mL/m; Mayo classifications 1B [5%], 1C [42%], 1D [21%], and 1E [32%]) and 11 controls in normal weight category (NWC) (age, 25±3 years; 45% women; BMI, 22.5 [21.7-24.2] kg/m2; eGFR, 113±15mL/min/1.73m2; HTKV, 159±31mL/m) at the University of Colorado Anschutz Medical Campus. PREDICTORS: ADPKD status (yes/no) and severity (Mayo classifications). OUTCOME: HTKV and cyst burden by magnetic resonance imaging, kidney oxidative metabolism, and perfusion by 11C-acetate positron emission tomography/computed tomography, insulin sensitivity by hyperinsulinemic-euglycemic clamps (presented as ratio of M-value of steady state insulin concentration [M/I]). ANALYTICAL APPROACH: For categorical variables, χ2/Fisher's exact tests, and for continuous variables t tests/Mann-Whitney U tests. Pearson correlation was used to estimate the relationships between variables. RESULTS: Compared with NWC individuals, the participants with ADPKD exhibited lower mean±SD M/I ratio (0.586±0.205 vs 0.424±0.171 [mg/kg lean/min]/(µIU/mL), P=0.04), lower median cortical perfusion (1.93 [IQR, 1.80-2.09] vs 0.68 [IQR, 0.47-1.04] mL/min/g, P<0.001) and lower median total kidney oxidative metabolism (0.17 [IQR, 0.16-0.19] vs. 0.14 [IQR, 0.12-0.15] min-1, P=0.001) in voxel-wise models excluding cysts. HTKV correlated inversely with cortical perfusion (r: -0.83, P < 0.001), total kidney oxidative metabolism (r: -0.61, P<0.001) and M/I (r: -0.41, P = 0.03). LIMITATIONS: Small sample size and cross-sectional design. CONCLUSIONS: Adults with ADPKD and preserved kidney function exhibited impaired renal perfusion and kidney oxidative metabolism across a wide range of cysts and kidney enlargements. FUNDING: Grants from government (National Institutes of Health, Centers for Disease Control and Prevention) and not-for-profit (JDRF) entities. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study numbers NCT04407481 and NCT04074668. PLAIN-LANGUAGE SUMMARY: In our study, we explored how a common genetic kidney condition, autosomal dominant polycystic kidney disease (ADPKD), relates to kidney metabolism. ADPKD leads to the growth of numerous cysts in the kidneys, which can impact their ability to work properly. We wanted to understand the kidneys' ability to process oxygen and blood flow in ADPKD. Our approach involved using advanced imaging techniques to observe kidney metabolism and blood flow in people with ADPKD compared with healthy individuals. We discovered that those with ADPKD had significant changes in kidney oxygen metabolism even when their kidney function was still normal. These findings are crucial as they provide deeper insights into ADPKD, potentially guiding future treatments to target these changes.

Balancing Act of the Intestinal Antimicrobial Proteins on Gut Microbiota and Health.

The human gut houses a diverse and dynamic microbiome critical for digestion, metabolism, and immune development, exerting profound effects on human health. However, these microorganisms pose a potential threat by breaching the gut barrier, entering host tissues, and triggering infections, uncontrolled inflammation, and even sepsis. The intestinal epithelial cells form the primary defense, acting as a frontline barrier against microbial invasion. Antimicrobial proteins (AMPs), produced by these cells, serve as innate immune effectors that regulate the gut microbiome by directly killing or inhibiting microbes. Abnormal AMP production, whether insufficient or excessive, can disturb the microbiome equilibrium, contributing to various intestinal diseases. This review delves into the complex interactions between AMPs and the gut microbiota and sheds light on the role of AMPs in governing host-microbiota interactions. We discuss the function and mechanisms of action of AMPs, their regulation by the gut microbiota, microbial evasion strategies, and the consequences of AMP dysregulation in disease. Understanding these complex interactions between AMPs and the gut microbiota is crucial for developing strategies to enhance immune responses and combat infections within the gut microbiota. Ongoing research continues to uncover novel aspects of this intricate relationship, deepening our understanding of the factors shaping gut health. This knowledge has the potential to revolutionize therapeutic interventions, offering enhanced treatments for a wide range of gut-related diseases.

Challenges and potential improvements in the Accreditation Standards of the Korean Institute of Medical Education and Evaluation 2019 (ASK2019) derived through meta-evaluation: a cross-sectional study

PURPOSE: This study aimed to identify challenges and potential improvements in Korea's medical education accreditation process according to the Accreditation Standards of the Korean Institute of Medical Education and Evaluation 2019 (ASK2019). Meta-evaluation was conducted to survey the experiences and perceptions of stakeholders, including self-assessment committee members, site visit committee members, administrative staff, and medical school professors. METHODS: A cross-sectional study was conducted using surveys sent to 40 medical schools. The 332 participants included self-assessment committee members, site visit team members, administrative staff, and medical school professors. The t-test, one-way analysis of variance and the chi-square test were used to analyze and compare opinions on medical education accreditation between the categories of participants. RESULTS: Site visit committee members placed greater importance on the necessity of accreditation than faculty members. A shared positive view on accreditation's role in improving educational quality was seen among self-evaluation committee members and professors. Administrative staff highly regarded the Korean Institute of Medical Education and Evaluation's reliability and objectivity, unlike the self-evaluation committee members. Site visit committee members positively perceived the clarity of accreditation standards, differing from self-assessment committee members. Administrative staff were most optimistic about implementing standards. However, the accreditation process encountered challenges, especially in duplicating content and preparing self-evaluation reports. Finally, perceptions regarding the accuracy of final site visit reports varied significantly between the self-evaluation committee members and the site visit committee members. CONCLUSION: This study revealed diverse views on medical education accreditation, highlighting the need for improved communication, expectation alignment, and stakeholder collaboration to refine the accreditation process and quality.

Facial Skin Rejuvenation Using Poly-dl-Lactic Acid Injected With a Laser-Generated Needle-Free Microjet Injector.

BACKGROUND: A laser-induced needle-free microjet injector was developed for rapid, high-speed drug delivery of microliters into the skin. OBJECTIVE: This study evaluated the clinical rejuvenation effect of repeated dermal injections of the collagen simulator poly-dl-lactic acid (PDLA) using a laser-induced needle-free microjet injector. METHODS: Five PDLA injection sessions using a laser-induced needle-free microjet injector were conducted in patients concerned about aging skin. Facial uplifting, darkness, redness, roughness, pore size, subjective satisfaction, and side effects were evaluated before each session and 4 weeks after treatment completion. Histological evaluation was also performed with immunohistochemical staining of collagen and elastic fibers. RESULTS: The clinical results of 27 female patients were evaluated. The treatment resulted in a noticeable skin surface uplifting (0.711 ± 0.42 mm) and significant improvements in darkness (p = .013), redness (p = .009), and roughness (p = .036), with no significant difference in the pore size (p = .770). Patients were reported being satisfied with the overall therapeutic effects, despite mild and tolerable adverse effects. Histological findings revealed growth and thickening of collagen and elastic fibers, with marked increase in collagen I and III levels. CONCLUSION: Repeated dermal injections of PDLA using a laser-induced microjet injector offer excellent drug delivery, achieving high efficacy in skin rejuvenation, patient satisfaction, and safety.

Effects of Limosilactobacillus reuteri ID-D01 Probiotic Supplementation on Exercise Performance and Gut Microbiota in Sprague-Dawley Rats.

The gut microbiota composition in animals and humans has recently been found to be influenced by exercise. Although Limosilactobacillus reuteri strains have notable probiotic properties that promote human health, understanding of its effects in combination with exercise and physical activity is limited. Therefore, this study examined the effects of L. reuteri ID-D01, a human-derived probiotic, on exercise performance and fatigue in Sprague-Dawley rats. Organ weight, maximal running distance, serum biochemistry, muscle performance, microbial community composition, and short-chain fatty acid (SCFA) levels were assessed. Results indicated that ID-D01 supplementation significantly improved endurance performance. Rats in the probiotic group demonstrated a significant increase in maximal running distance compared with that in the control group (p < 0.05). Additionally, levels of fatigue markers, such as lactate and creatine phosphokinase, were significantly reduced in the ID-D01-administered groups, suggesting its potential to alleviate exercise-induced fatigue. Microbiome analysis revealed a distinct shift in gut microbiota composition in response to ID-D01 administration. The group that received ID-D01 probiotics exhibited a significant increase in the abundance of SCFA-producing bacteria, particularly Akkermansia spp., compared with that in the control groups. Furthermore, they showed elevated production of SCFAs, such as acetate and butyrate. In conclusion, this study demonstrated that ID-D01 can enhance exercise performance and reduce fatigue. Herein, we highlighted that human-derived probiotics could improve physical performance, as observed by changes in gut microbiota composition and SCFA production.

CRIF1 deficiency induces FOXP3LOW inflammatory non-suppressive regulatory T cells, thereby promoting antitumor immunity.

Recently identified human FOXP3lowCD45RA- inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (Tregs). In spite of their implication in tumors, the mechanism for generation of FOXP3lowCD45RA- INS cells in vivo is unclear. We showed that the FOXP3lowCD45RA- cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3lowINS-Tregs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinflammatory cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased α-ketoglutarate-derived 2-hydroxyglutarate down-regulated Foxp3 expression by methylating the Foxp3 gene regulatory regions. Furthermore, CRIF1 deficiency-induced Foxp3lowINS-Tregs suppressed tumor growth in an IFN-γ-dependent manner. Thus, CRIF1 deficiency-mediated mitochondrial dysfunction results in the induction of Foxp3lowINS-Tregs including FOXP3lowCD45RA- cells that promote antitumor immunity.