BACKGROUND/OBJECTIVES: Supplementation of nicotinamide adenine dinucleotide (NAD) precursors has been investigated for its potential to counteract age-related physiological decline. While decreased NAD + level is associated with conditions such as obesity and dyslipidemia, few studies have explored its metabolic impact in relatively young animals.Here, we hypothesized that nicotinamide mononucleotide (NMN) could alleviate highfat diet-induced metabolic stress in young mice and sought to elucidate the underlying mechanisms.MATERIALS/METHODS: We first conducted a secondary analysis of hepatic transcriptome datasets from multiple NMN intervention studies to identify target pathways. Next, 11-weekold lean and obese C57BL/6N mice administrated NMN (500 mg/kg/day) for 1 mon were analyzed for metabolic parameters and gene expression for the target pathways. In vitro study using AML12 cell line was then conducted to confirm the effects of NMN. Additionally, transcriptomic data from liver-specific nicotinamide phosphoribosyltransferase (NAMPT)-deficient mice were analyzed to examine the relationship between NAD + metabolism, endoplasmic reticulum (ER) stress, and circadian rhythm. RESULTS: The secondary analysis of hepatic transcriptome datasets revealed potential target pathways related to circadian regulation and hepatic ER stress. In mouse study, short-term NMN administration significantly decreased body weight and fat mass. NMN also alleviated hepatic ER stress response in vivo and in vitro. Additional analysis revealed that the mice with diet-induced metabolic stress or NAMPT deficiency led to phase shifts of the hepatic circadian core clock oscillation by advancing the peak time, while time-restricted feeding shifted the opposite, indicating the metabolic regulation of the circadian phase. CONCLUSION Short-term NMN administration effectively attenuated obese condition in young mice and mitigated hepatic ER stress. The altered ER stress was regulated by NAMPT, potentially through the phase shift of the hepatic circadian rhythm.

Circadian rhythms orchestrate daily fluctuations in feeding behavior, hormonal activity, and metabolic function through coordinated interactions between the central clock and peripheral oscillators. Dietary patterns, defined by both macronutrient composition and the timing of food intake, function as potent cues that reshape these rhythms. This narrative review summarizes experimental evidence describing how diet influences circadian organization and how circadian disruption alters metabolic outcomes primarily in murine models. Genetic disruption of core clock components such as CLOCK, BMAL1, CRY, or PER abolishes feeding rhythmicity and desynchronizes metabolic pathways, resulting in obesity, impaired glucose regulation, and hepatic lipid accumulation. Dietary composition also influences circadian organization, as high-fat, ketogenic, or modified-protein diets shift the phase or amplitude of peripheral clock gene rhythms and alter metabolic outputs across tissues. Feeding-time misalignment produces substantial phase shifts in hepatic and adipose oscillations and aggravates diet-induced metabolic dysfunction. In contrast, restricting food intake to consistent daily windows restores rhythmic metabolic states in the liver, adipose tissue, and intestine and improves systemic homeostasis even without reducing caloric intake. Together, these findings show that both macronutrient composition and feeding-time alignment influence the phase and synchrony of peripheral circadian rhythms and the metabolic processes governed by these rhythms. Understanding these relationships provides mechanistic insight into diet–circadian interactions and supports the development of circadian-aligned dietary strategies aimed at promoting metabolic stability.

Purpose: To predict the presence of tractional retinal detachment (TRD) in eyes with dense vitreous hemorrhage (VH) and proliferative diabetic retinopathy (PDR) by evaluating the status of posterior vitreous detachment (PVD) in fellow eyes using optical coherence tomography (OCT). Methods: A total of 44 eyes from 22 patients who underwent vitrectomy due to dense VH with PDR were enrolled. Using OCT, the PVD status in the fellow eye was divided into two groups (incomplete and complete PVD). The incomplete PVD group included eyes without PVD and eyes with partial PVD. B-scan ultrasonography was performed on eyes with dense VH to evaluate the presence of TRD. Both OCT and B-scan images were reviewed by four ophthalmologists (two novices and two experienced), and the interobserver agreement was evaluated. Results: There was a difference in the interobserver agreement regarding the presence of TRD in eyes with dense VH evaluated by B scan between novice and experienced ophthalmologists (novice, κ = 0.421 vs. experienced, κ = 0.814), although there was no difference between novice and experienced ophthalmologists in the interobserver agreement regarding the status of PVD in the fellow eye evaluated by OCT (novice, κ = 1.000 vs. experienced, κ = 1.000). All observed TRD during vitrectomy occurred in eyes with incomplete PVD in the fellow eye. Logistic regression analysis revealed a statistically significant relation between TRD and the age of the patient (odds ratio [OR], 0.874; p = 0.047), and between TRD and incomplete PVD in the fellow eye evaluated by OCT (OR, 13.904; p = 0.042). Conclusions Evaluation of the PVD status in the fellow eye using OCT may be a useful predictor for detecting the presence of TRD in eyes with dense VH and PDR.

Neurocritical patients who can self-report pain use the 0-10 numerical rating scale (NRS, verbal or visual form). However, critically ill patients whose nervous systems cannot express pain use the behavioral pain scale (BPS) and the critical care pain observation tool (CPOT) behavioral pain assessment tools. These tools reveal pain-related changes in movement, facial expression, posture, and physiological indicators such as heart rate, blood pressure, and respiratory rate. In pain control, it is first essential to reduce unnecessary painkillers through non-drug therapy and maximize the effect of the administered analgesics. For nonneuropathic pain, narcotic analgesics such as fentanyl, hydromorphone, morphine, and remifentanil are administered intravenously. Gabapentin, pregabalin, and carbamazepine are recommended along with narcotic analgesics for neuropathic pain control. In addition, nonnarcotic analgesics for multi-modal analgesia are used to reduce the use of narcotic analgesics or the side effects of narcotic analgesics. In the intensive care unit (ICU), the sedation-agitation scale (SAS) and the Richmond agitation-sedation scale (RASS) are used to determine the depth of sedation to be maintained during shallow or deep sedation, considering the condition of the critically ill patient. When selecting sedatives for critically ill patients, preferentially consider nonbenzodiazepines such as propofol or dexmedetomidine rather than benzodiazepines such as midazolam or lorazepam. In addition, patients use painkillers or sedatives for over a week, and neurological changes or physiological dependence may occur. Therefore, clinicians should evaluate the critically ill patient’s condition, and sedatives and painkillers should be reduced or discontinued.

An endolichenic fungus,Xylaria grammica strain EL000614, showed strong nematicidal effects against plant pathogenic nematode, Meloidogyne incognita by producing grammicin. We report genome assembly of X. grammica EL000614 comprised of 25 scaffolds with a total length of 54.73 Mb, N50 of 4.60 Mb, and 99.8% of BUSCO completeness. GC contents of this genome were 44.02%. Gene families associated with biosynthesis of secondary metabolites or regulatory proteins were identified out of 13,730 gene models predicted.

An endolichenic fungus, Xylaria grammica strain EL000614, showed strong nematicidal effects against plant pathogenic nematode, Meloidogyne incognita by producing grammicin.We report genome assembly of X. grammica EL000614 comprised of 25 scaffolds with a total length of 54.73 Mb, N50 of 4.60 Mb, and 99.8% of BUSCO completeness. GC contents of this genome were 44.02%. Gene families associated with biosynthesis of secondary metabolites or regulatory proteins were identified out of 13,730 gene models predicted.

An endolichenic fungus,Xylaria grammica strain EL000614, showed strong nematicidal effects against plant pathogenic nematode, Meloidogyne incognita by producing grammicin. We report genome assembly of X. grammica EL000614 comprised of 25 scaffolds with a total length of 54.73 Mb, N50 of 4.60 Mb, and 99.8% of BUSCO completeness. GC contents of this genome were 44.02%. Gene families associated with biosynthesis of secondary metabolites or regulatory proteins were identified out of 13,730 gene models predicted.

An endolichenic fungus, Xylaria grammica strain EL000614, showed strong nematicidal effects against plant pathogenic nematode, Meloidogyne incognita by producing grammicin.We report genome assembly of X. grammica EL000614 comprised of 25 scaffolds with a total length of 54.73 Mb, N50 of 4.60 Mb, and 99.8% of BUSCO completeness. GC contents of this genome were 44.02%. Gene families associated with biosynthesis of secondary metabolites or regulatory proteins were identified out of 13,730 gene models predicted.

An endolichenic fungus Xylaria grammica EL000614 produces grammicin, a potent nematicidal pyrone derivative that can serve as a new control option for root-knot nematodes. We optimized an Agrobacterium tumefaciens-mediated transformation (ATMT) protocol for X.grammica to support genetic studies. Transformants were successfully generated after co-cultivation of homogenized young mycelia of X.grammica with A. tumefaciens strain AGL-1 carrying a binary vector that contains the bacterial hygromycin B phosphotransferase (hph) gene and the eGFP gene in T-DNA. The resulting transformants were mitotically stable, and PCR analysis showed the integratin of both genes in the genome of transformants.Expression of eGFP was confirmed via fluorescence microscopy. Southern analysis showed that 131 (78.9%) out of 166 transformants contained a single T-DNA insertion. Crucial factors for producing predominantly single T-DNA transformants include 48 h of co-cultivation, pretreatment of A. tumefaciens cells with acetosyringone before co-cultivation, and using freshly prepared mycelia. The established ATMT protocol offers an efficient tool for random insertional mutagenesis and gene transfer in studying the biology and ecology ofX.grammica.

Purpose: To evaluate the association between long-term glycated hemoglobin A (HbA1c) variability and treatment outcomes ofanti-vascular endothelial growth factor (VEGF) injection in diabetic macular edema patients. Methods: The medical records of 49 eyes (38 patients) that received anti-VEGF injection for diabetic macular edema were reviewedretrospectively. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) before injection and at onemonth and six months after injection were analyzed. HbA1c variability (HbA1c coefficient of variation [CV]) was calculated usingthe HbA1c results from the year prior to (before) and the year after injection and compared with clinical results. Results: In the group with a low mean HbA1c level before injection, the group with lower HbA1c CV showed greater reduction inmacular edema one month after injection (low HbA1c CV, 122.4 ± 123.2 μm versus high HbA1c CV, 5.2 ± 37.0 μm, p= 0.027).In the group with high mean HbA1c, there was no significant difference between HbA1c variability and clinical features. In a multivariateanalysis, the factor related to the reduction of macular edema was initial CMT (one month adjusted hazard ratio (aHR)0.5, p< 0.001; six months aHR 0.3, p= 0.023). The factor associated with visual gain was initial visual acuity (LogMAR) (onemonth aHR 0.4, p< 0.001; six months aHR 0.4, p< 0.001). The association between mean HbA1c or HbA1c variability and clinicaloutcome was not significant. Conclusions Unlike initial CMT or BCVA, mean HbA1c and HbA1c variability were not significantly associated with clinical outcomesof anti-VEGF injection in diabetic macular edema patients.