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Although GaP, a III-V compound semiconductor, has been extensively utilized in the optoelectronic industry for decades as a traditional material, the inherent indirect bandgap nature of GaP limits its efficiency. Here, we demonstrate an indirect-to-direct bandgap transition of GaP through the formation of quantum shells on the surface of ZnS nanocrystals. The ZnS/GaP quantum shell with a reverse-type I heterojunction, consisting of a monolayer-thin GaP shell grown atop a ZnS core, exhibits a record-high photoluminescence quantum yield of 45.4% in the violet emission range (wavelength = 409 nm), validating its direct bandgap nature. Density functional theory calculations further reveal that ZnS nanocrystals, as the growth platform for GaP quantum shells, play a crucial role in the direct bandgap formation through hybridization of electronic states with GaP. These findings suggest potential for achieving direct bandgaps in compounds that are constrained by their inherent indirect energy gaps, offering a strategy for tailoring energy structures to significantly improve efficiencies in optoelectronics and photovoltaics., (© 2024. The Author(s).)

Sleep is one of the most essential physiological phenomena for maintaining health. Sleep disturbances, such as insomnia, are often accompanied by psychiatric or physical conditions such as impaired attention, anxiety, and stress. Medication used to treat insomnia have concerns about potential side effects with long-term use, so interest in the use of alternative medicine is increasing. In this study, we investigated the hypnotic effects of β-lapachone (β-Lap), a natural naphthoquinone compound, using pentobarbital-induced sleep test, immunohistochemistry, real-time PCR, and western blot in mice. Our results indicated that β-Lap exerts a significant hypnotic effect by showing a decrease in sleep onset latency and an increase in total sleep time in pentobarbital-induced sleep model. The results of c-Fos immunostaining showed that β-Lap decreased neuronal activity in the basal forebrain and lateral hypothalamus, which are wakefulness-promoting brain regions, while increasing in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly abolished by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A 1 receptor (A 1 R) antagonist. Western blot analysis showed that β-Lap increased extracellular signalregulated kinase phosphorylation and nuclear factor-kappa B translocation from the cytoplasm to the nucleus; these effects were inhibited by DPCPX. Additionally, β-Lap increased the mRNA levels of A 1 R. Taken together, these results suggest that β-Lap exerts hypnotic effects, potentially through A 1 R.

Objectives: To determine whether there is a difference in antibiotic administration time and prognosis in afebrile sepsis patients compared to febrile sepsis patients., Methods: This was retrospective multicenter observational study. Data collected from three referral hospitals. Data were collected from May 2014 through February 2016 under the SEPSIS-2 criteria and from March 2016 to April 2020 under the newly released SEPSIS-3 criteria. Patients were divided into two groups based on body temperature: afebrile (<37.3 °C) and febrile (≥37.3 °C). The relationship between initial body temperature and 28-day mortality were analyzed using multivariable logistic regression. The subgroup analysis was conducted on patients with complete Hour-1 bundle performance records., Results: We included 4293 patients in this study. Initial body temperatures in 28-day survivors were significantly higher than in 28-day non-survivors (37.5 °C ± 1.2 °C versus 37.1 °C ± 1.2 °C, p < 0.01). Multivariable logistic regression analysis was performed in afebrile and febrile sepsis patients. Adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.76 (95% Confidence interval 1.46-2.12). As a result of performing the Hour-1 bundle, the number of patients who received antibiotics within 1 h was smaller in the afebrile sepsis patients (323/2076, 15.6%) than in the febrile sepsis patients (395/2156, 18.3%) (p = 0.02). In the subgroup analysis of patients with complete Hour-1 bundle performance records adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.68 (95% Confidence interval 1.34-2.11). The febrile sepsis patients received antibiotics faster than the afebrile sepsis patients (175.5 ± 207.9 versus 209.3 ± 277.9, p < 0.01)., Conclusions: Afebrile sepsis patients were associated with higher 28-day mortality compared to their febrile counterparts and were delayed in receiving antibiotics. This underscores the need for improved early detection and treatment strategies for the afebrile sepsis patients., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Manipulating the grain boundary and chiral structure of enantiomorphic inorganic thermoelectric materials facilitates a new degree of freedom for enhancing thermoelectric energy conversion. Chiral twist mechanisms evolve by the screw dislocation phenomenon in the nanostructures; however, contributions of such chiral transport have been neglected for bulk crystals. Tellurium (Te) has a chiral trigonal crystal structure, high band degeneracy, and lattice anharmonicity for high thermoelectric performance. Here, Sb-doped Te crystals are grown to minimize the severe grain boundary effects on carrier transport and investigate the interface of chiral Te matrix and embedded achiral Sb 2 Te 3 precipitates, which induce unusual lattice twists. The low grain boundary scattering and conformational grain restructuring provide electrical-favorable semicoherent interfaces. This maintains high electrical conductivity leading to a twofold increase in power factor compared to polycrystal samples. The embedded Sb 2 Te 3 precipitates concurrently enable moderate phonon scattering leading to a remarkable decrease in lattice thermal conductivity and a high dimensionless figure of merit (zT) of 1.1 at 623 K. The crystal growth and chiral atomic reorientation unravel the emerging benefits of interface engineering as a crucial contributor to effectively enhancing carrier transport and minimizing phonon propagation in thermoelectric materials., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65-0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69-0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86-0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90-1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aim: Tegoprazan, a novel potassium-competitive acid blocker, has been approved for Helicobacter pylori eradication in Korea. We compared the efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for H. pylori eradication in real-world clinical practice., Methods: We retrospectively analyzed data from patients with H. pylori infection treated with tegoprazan- or rabeprazole-based concomitant therapies. The primary endpoint was H. pylori eradication rate. The secondary endpoint was adverse events., Results: Among the 1474 included patients, 620 and 854 received tegoprazan- and rabeprazole-based concomitant therapies, respectively. Intention-to-treat analysis showed no significant difference in the eradication rates between the tegoprazan- and rabeprazole-based concomitant therapy groups (74.7% [95% confidence interval [CI], 71.1-78.0%] vs 72.7% [95% CI, 69.7-75.6%], P = 0.400). Per-protocol analysis also demonstrated similar eradication rates for the groups (tegoprazan vs rabeprazole: 88.0% [95% CI, 85.0-90.6%] vs 85.9% [95% CI, 83.2-88.3%], P = 0.288). Although the overall adverse event rate did not differ between groups (tegoprazan vs rabeprazole, 39.2% vs 40.6%, P = 0.578), abdominal discomfort was less frequent in the tegoprazan group than in the rabeprazole group (1.3 vs 4.8%, P = 0.001)., Conclusions: Tegoprazan- and rabeprazole-based concomitant therapies for H. pylori eradication showed comparable efficacy and overall safety. The effect of tegoprazan on dose increases or other regimens, such as bismuth-containing quadruple therapy, should be further evaluated, because the efficacy of tegoprazan-based concomitant therapy may be suboptimal in regions where the clarithromycin resistance rate is high., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Although extreme ultraviolet lithography (EUVL) has emerged as a leading technology for achieving high quality sub-10 nm patterns, the insufficient pattern height of photoresist patterns remains a challenge. Directed self-assembly (DSA) of block copolymers (BCPs) is expected to be a complementary technology for EUVL due to its ability to form periodic nanostructures. However, for a combination with EUV patterns, it is essential to develop advanced BCP systems that are suited to inorganic-containing EUV photoresists and offer improved resolution limits, pattern quality, and etch resistance. Here, we report a reverse-gradient BCP system, poly[(styrene- gradient -pentafluorostyrene)- b -4- tert -butyldimetilsiloxystyrene] [P(S- g -PFS)- b -P4BDSS] BCP, which enables universally vertically oriented lamellae even in the absence of a neutral layer, while also containing a Si-containing block with high etch resistance. The gradient block, characterized by a gradual compositional transition from the block junction to the tail, plays a crucial role in creating an adequate surface energy contrast that energetically drives the formation of perpendicular lamellae without neutral layer. When used as a pattern height enhancement layer in EUVL, a high aspect ratio (3.29) of patterns was achieved, thereby offering a supplementary solution for next-generation EUVL.

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage., (© 2024. The Author(s).)

Three-dimensional optical nanostructures have garnered significant interest in photonics due to their extraordinary capabilities to manipulate the amplitude, phase, and polarization states of light. However, achieving complex three-dimensional optical nanostructures with bottom-up fabrication has remained challenging, despite its nanoscale precision and cost-effectiveness, mainly due to inherent limitations in structural controllability. Here, we report the optical characteristics of intricate two- and three-dimensional nanoarchitectures made of colloidal quantum dots fabricated with multi-dimensional transfer printing. Our customizable fabrication platform, directed by tailored interface polarity, enables flexible geometric control over a variety of one-, two-, and three-dimensional quantum dot architectures, achieving tunable and advanced optical features. For example, we demonstrate a two-dimensional quantum dot nanomesh with tuned subwavelength square perforations designed by finite-difference time-domain calculations, achieving an 8-fold enhanced photoluminescence due to the maximized optical resonance. Furthermore, a three-dimensional quantum dot chiral structure is also created via asymmetric stacking of one-dimensional quantum dot layers, realizing a pronounced circular dichroism intensity exceeding 20°., (© 2024. The Author(s).)

Insomnia is a common sleep disorder with significant societal and economic impacts. Current pharmacotherapies for insomnia are often accompanied by side effects, necessitating the development of new therapeutic drugs. In this study, the hypnotic effects and mechanisms of Sedum kamtschaticum 30% ethanol extract (ESK) and one of its active compounds, myricitrin, were investigated using pentobarbital-induced sleep experiments, immunohistochemistry (IHC), receptor binding assays, and enzyme-linked immunosorbent assay (ELISA). The pentobarbital-induced sleep experiments revealed that ESK and myricitrin reduced sleep latency and prolonged total sleep time in a dose-dependent manner. Based on c-Fos immunostaining, ESK, and myricitrin enhanced the GABAergic neural activity in sleep-promoting ventrolateral preoptic nucleus (VLPO) GABAergic. By measuring the level of GABA released from VLPO GABAergic neurons, ESK and myricitrin were found to increase GABA release in the hypothalamus. These effects were significantly inhibited by SCH. Moreover, ESK exhibited a concentration-dependent binding affinity for the adenosine A 2A receptors (A 2A R). In conclusion, ESK and myricitrin have hypnotic effects, and their underlying mechanisms may be related to the activation of A 2A R.

Bisphenol A (BPA) is widely used in plastic and paper products, and its exposure can occur through skin contact or oral ingestion. The hazardous effects of BPA absorbed through the skin may be more severe; however, few studies have investigated the skin toxicity of BPA. This study investigated the effects of BPA on human epidermal keratinocyte cell lines, which is relevant for skin exposure. BPA treatment reduced cell viability in a time- and concentration-dependent manner and elevated oxidative and endoplasmic reticulum (ER) stress. N-acetylcysteine (NAC), an oxidative stress inhibitor, reduced BPA-induced reactive oxygen species (ROS) levels. However, only 10% of the decreased cell viability was restored at the highest NAC concentration. Treatment with tauroursodeoxycholic acid (TUDCA), which is an ER stress inhibitor, effectively countered the increase in ER stress-related proteins induced by BPA. Moreover, TUDCA treatment led to a reduction in oxidative stress, as demonstrated by the decrease in ROS levels, maintenance of mitochondrial membrane potential, and modulation of stress signaling proteins. Consequently, TUDCA significantly improved BPA-induced cytotoxicity in a concentration-dependent manner. Notably, combined treatment using TUDCA and NAC further reduced the BPA-induced ROS levels; however, no significant difference in cell viability was observed compared with that for TUDCA treatment alone. These findings indicated that the oxidative stress observed following BPA exposure was exacerbated by ER stress. Moreover, the principal factor driving BPA-induced cytotoxicity was indeed ER stress, which has potential implications for developing therapeutic strategies for diseases associated with similar stress responses., (© 2024 The Authors. Environmental Toxicology published by Wiley Periodicals LLC.)

Cellular senescence contributes to inflammatory kidney disease via the secretion of inflammatory and profibrotic factors. Protease-activating receptor 2 (PAR2) is a key regulator of inflammation in kidney diseases. However, the relationship between PAR2 and cellular senescence in kidney disease has not yet been described. In this study, we found that PAR2-mediated metabolic changes in renal tubular epithelial cells induced cellular senescence and increased inflammatory responses. Using an aging and renal injury model, PAR2 expression was shown to be associated with cellular senescence. Under in vitro conditions in NRK52E cells, PAR2 activation induces tubular epithelial cell senescence and senescent cells showed defective fatty acid oxidation (FAO). Cpt1α inhibition showed similar senescent phenotype in the cells, implicating the important role of defective FAO in senescence. Finally, we subjected mice lacking PAR2 to aging and renal injury. PAR2-deficient kidneys are protected from adenine- and cisplatin-induced renal fibrosis and injury, respectively, by reducing senescence and inflammation. Moreover, kidneys lacking PAR2 exhibited reduced numbers of senescent cells and inflammation during aging. These findings offer fresh insights into the mechanisms underlying renal senescence and indicate that targeting PAR2 or FAO may be a promising therapeutic approach for managing kidney injury., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Recombinant adenovirus (rAdV) vector is the most promising vehicle to deliver an exogenous gene into target cells and is preferred for gene therapy. Exogenous gene expression from rAdV is often too inefficient to induce phenotypic changes and the amount of administered rAdV must be very high to achieve a therapeutic dose. However, it is often hampered because a high dose of rAdV is likely to induce cytotoxicity by activating immune responses. nc886, a 102-nucleotide non-coding RNA that is transcribed by RNA polymerase III, acts as an immune suppressor and a facilitator of AdV entry into the nucleus. Therefore, in this study, we have constructed an rAdV expressing nc886 (AdV:nc886) to explore whether AdV:nc886 overcomes the aforementioned drawbacks of conventional rAdV vectors. When infected into mouse cell lines and mice, AdV:nc886 expresses a sufficient amount of nc886, which suppresses the induction of interferon-stimulated genes and apoptotic pathways triggered by AdV infection. As a result, AdV:nc886 is less cytotoxic and produces more rAdV-delivered gene products, compared with the parental rAdV vector lacking nc886. In conclusion, this study demonstrates that the nc886-expressing rAdV could become a superior gene delivery vehicle with greater safety and higher efficiency for in vivo gene therapy., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Body odor is considered a diagnostic indicator of various infectious and chronic diseases. But, few studies have examined the odor markers for various toxic effects in the mammalian system. This study attempted to identify the novel diagnostic odor biomarkers for chemical-induced hepatotoxicity in animals. The changes in the concentration of odors were analyzed in the urine of Sprague Dawley (SD) rats treated with two dosages (100 or 200 mg/kg) of 1,2,3-trichloropropane (TCP) using gas chromatography-mass spectrometry (GC-MS). The TCP treatment induced significant toxicity, including a decrease in body weight, an increase in serum biochemical factors, and histopathological changes in the liver of SD rats. During this hepatotoxicity, the concentrations of six odors (ethyl alcohol, acrolein (2-propenal), methanesulfonyl chloride, methyl ethyl ketone, cyclotrisiloxane, and 2-heptanone) in urine changed significantly after the TCP treatment. Among them, acrolein, an acrid and pungent compound, showed the highest rate of increase in the TCP-treated group compared to the Vehicle-treated group. In addition, this increase in acrolein was accompanied by enhanced spermine oxidase (SMOX) expression, an acrolein metabolic enzyme, and the increased level of IL-6 transcription as a regulator factor that induces SMOX production. The correlation between acrolein and other parameters was conformed using correlagram analyses. These results provide scientific evidence that acrolein have potential as a novel diagnostic odor biomarker for TCP-induced hepatotoxicity., Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00253-0., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© The Author(s) under exclusive licence to Korean Society of Toxicology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Decreased medial cheek fat volume during aging leads to loss of a youthful facial shape. Increasing facial volume by methods such as adipose-derived stem cell (ASC) injection can produce facial rejuvenation. High-intensity focused ultrasound (HIFU) can increase adipogenesis in subcutaneous fat by modulating cilia on ASCs, which is accompanied by increased HSP70 and decreased NF-κB expression. Thus, we evaluated the effect of HIFU on increasing facial adipogenesis in swine ( n = 2) via modulation of ASC cilia. Expression of CD166 , an ASC marker, differed by subcutaneous adipose tissue location. CD166 expression in the zygomatic arch (ZA) was significantly higher than that in the subcutaneous adipose tissue in the mandible or lateral temporal areas. HIFU was applied only on the right side of the face, which was compared with the left side, where HIFU was not applied, as a control. HIFU produced a significant increase in HSP70 expression, decreased expression of NF-κB and a cilia disassembly factor ( AURKA ), and increased expression of a cilia increasing factor ( ARL13B ) and PPARG and CEBPA , which are the main regulators of adipogenesis. All of these changes were most prominent at the ZA. Facial adipose tissue thickness was also increased by HIFU. Adipose tissue volume, evaluated by magnetic resonance imaging, was increased by HIFU, most prominently in the ZA. In conclusion, HIFU increased ASC marker expression, accompanied by increased HSP70 and decreased NF-κB expression. Additionally, changes in cilia disassembly and length and expression of adipogenesis were observed. These results suggest that HIFU could be used to increase facial volume by modulating adipogenesis.

Diagnosing the current health status and disease burden in a population is crucial for public health interventions. The ability to compare the burden of different diseases through a single measure, such as disability-adjusted life years has become feasible and continues to be produced and updated through the Global Burden of Diseases (GBD) study. However, the disease burden values of the GBD study do not accurately reflect the unique situation in a specific country with various circumstances. In response, the Korean National Burden of Disease (KNBD) study was conducted to estimate the disease burden in Koreans by considering Korea's cultural context and utilizing the available data sources at the national level. Both studies identified non-communicable diseases, such as diabetes mellitus (DM), as the primary cause of disease burden among Koreans. However, the extent of public health interventions currently being conducted by the central and local governments does not align with the severity of the disease burden. This review suggests that despite the high burden of DM in South Korea, the current policies may not fully address its impact, underscoring the need for expanded chronic disease management programs and a shift towards prevention-focused healthcare paradigms.

Histone H3K9 methylated heterochromatin silences repetitive non-coding sequences and lineage-specific genes during development, but how tissue-specific genes escape from heterochromatin in differentiated cells is unclear. Here, we examine age-dependent transcriptomic profiling of terminally differentiated mouse retina to identify epigenetic regulators involved in heterochromatin reorganization. The single-cell RNA sequencing analysis reveals a gradual downregulation of Kdm3b in cone photoreceptors during aging. Disruption of Kdm3b ( Kdm3b +/- ) of 12-month-old mouse retina leads to the decreasing number of cones via apoptosis, and it changes the morphology of cone ribbon synapses. Integration of the transcriptome with epigenomic analysis in Kdm3b +/- retinas demonstrates gains of heterochromatin features in synapse assembly and vesicle transport genes that are downregulated via the accumulation of H3K9me1/2. Contrarily, losses of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that the KDM3B-centered epigenomic network is crucial for balancing of cone photoreceptor homeostasis via the modulation of gene set-specific heterochromatin features during aging., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through cell plasticity, some lung adenocarcinoma (LUAD) cells transform into neuroendocrine (NE) tumor cells. However, the mechanisms of NE cell plasticity remain unclear. CRACD (capping protein inhibiting regulator of actin dynamics), a capping protein inhibitor, is frequently inactivated in cancers. CRACD knockout (KO) is sufficient to de-repress NE-related gene expression in the pulmonary epithelium and LUAD cells. In LUAD mouse models, Cracd KO increases intratumoral heterogeneity with NE gene expression. Single-cell transcriptomic analysis showed that Cracd KO-induced NE cell plasticity is associated with cell de-differentiation and stemness-related pathway activation. The single-cell transcriptomic analysis of LUAD patient tumors recapitulates that the distinct LUAD NE cell cluster expressing NE genes is co-enriched with impaired actin remodeling. This study reveals the crucial role of CRACD in restricting NE cell plasticity that induces cell de-differentiation of LUAD., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Senecavirus A (SVA), identified in 2002, is known to cause porcine idiopathic vesicular disease (PIVD), which presents with symptoms resembling other vesicular diseases. This similarity complicates field diagnosis. Conventional molecular diagnostic techniques are limited by their cost, sensitivity, and requirement for complicated instrumentation. Therefore, developing an effective and accurate diagnostic method is crucial for timely identification and isolation of affected pigs, thereby preventing further disease spread., Methods: In this study, we developed a highly-specific and ultra-sensitive SVA detection method powered by CRISPR/Cas12a. To enhance the availability in laboratories with varied equipment conditions, microplate reader and ultraviolet light transilluminator were introduced. Moreover, PCR amplification has also been incorporated into this method to improve sensitivity. The specificity and sensitivity of this method were determined following the preparation of the recombinant Cas12a protein and optimization of the CRISPR/Cas12a-based trans-cleavage system., Results: The method demonstrated no cross-reactivity with ten kinds of viruses of swine. The minimum template concentration required to activate substantial trans-cleavage activity was determined to be 10 6 copies/µL of SVA templates. However, when PCR amplification was incorporated, the method achieved a detection limit of one copy of SVA templates per reaction. It also exhibited 100% accuracy in simulated sample testing. The complete testing process does not exceed three hours., Conclusions: Importantly, this method utilizes standard laboratory equipment, making it accessible for use in resource-limited settings and facilitating widespread and ultra-sensitive screening during epidemics. Overall, the development of this method not only broadens the array of tools available for detecting SVA but also holds significant promise for controlling the spread of PIVD., (© 2024. The Author(s).)

The accumulation of methylglyoxal (MGO) produced in high-temperature processed foods and excessive production in the body contributes to intestinal barrier dysfunction. In this study, we investigated the effects of chitooligosaccharides (COSs) of different molecular weights (<1 kDa, 1-3 kDa, 3-5 kDa, 5-10 kDa, and >10 kDa) on MGO-induced intestinal barrier dysfunction. We investigated the effect of COSs on inhibiting intracellular MGO accumulation/MGO-derived AGEs production and regulating the receptor for AGE (RAGE)-mediated downstream protein expression, including proteins related to apoptosis and inflammation, intestinal barrier integrity, and paracellular permeability. Pretreatment with COSs ameliorated MGO-induced increased RAGE protein expression, activation of apoptotic cascade/inflammatory response, loss of intestinal epithelial barrier integrity, and increased paracellular permeability, ameliorating intestinal dysfunction through MGO scavenging. 1-3 kDa COSs most effectively ameliorated MGO-induced intestinal dysfunction. Our results suggest the potential of COSs in improving intestinal health by ameliorating intestinal barrier dysfunction by acting as an MGO scavenger and highlighting the need for the optimization of the molecular weight of COSs to optimize its protective effects., Competing Interests: Declaration of competing interest The authors declare that there have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Silicon (Si) anodes, free from the dendritic growth concerns found in lithium (Li) metal anodes, offer a promising alternative for high-energy all-solid-state batteries (ASSBs). However, most advancements in Si anodes have been achieved under impractical high operating pressures, which can mask detrimental electrochemo-mechanical issues. Herein, we effectively address the challenges related to the low-pressure operation of Si anodes in ASSBs by introducing an silver (Ag) interlayer between the solid electrolyte layer (Li 6 PS 5 Cl) and anode and prelithiating the anodes. The Si composite electrodes, consisting of Si/polyvinylidene fluoride/carbon nanotubes, are optimized for suitable mechanical properties and electrical connectivity. Although the impact of the Ag interlayer is insignificant at an exceedingly high operating pressure of 70 MPa, it substantially enhances the interfacial contacts under a practical low operating pressure of 15 MPa. Thus, Ag-coated Si anodes outperform bare Si anodes (discharge capacity: 2430 vs 1560 mA h g -1 ). The robust interfacial contact is attributed to the deformable, adhesive properties and protective role of the in situ lithiated Ag interlayer, as evidenced by comprehensive ex situ analyses. Operando electrochemical pressiometry is used effectively to probe the strong interface for Ag-coated Si anodes. Furthermore, prelithiation through the thermal evaporation deposition of Li metal significantly improves the cycling performance., (© 2024 Wiley‐VCH GmbH.)

Di-d-psicose anhydride (DPA), derived from functional rare saccharide as d-psicose, is investigated for its strong chelating ability. Methylglyoxal (MGO), an important precursor of advanced glycation end-products (AGEs), promotes obesity, and causes complications such as diabetic nephropathy. On mesangial cells, DPA can substantially reduce the negative effects of MGO. DPA effectively trapping MGO in mesangial cells. The bonding properties of the DPA-MGO adduct were discussed by mass spectrometry and nuclear magnetic resonance (NMR). The NMR spectra of the DPA-MGO adduct provide evidence for chelation bonding. The inhibition of AGE formation and the mass spectrometry results of the DPA-MGO adduct indicate that DPA can scavenge MGO at a molar ratio of 1:1. DPA suppressed 330 % of the up-regulated receptor for an AGEs protein expression to a normal level and restored the suppressed glyoxalase 1 level to 86 % of the normal group. This research provides important evidence and theoretical basis for the development of AGE inhibitors derived from rare saccharide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Manipulating thermal properties of materials can be interpreted as the control of how vibrations of atoms (known as phonons) scatter in a crystal lattice. Compared to a perfect crystal, crystalline solids with defects are expected to have shorter phonon mean free paths caused by point defect scattering, leading to lower lattice thermal conductivities than those without defects. While this is true in many cases, alloying can increase the phonon mean free path in the Cd-doped AgSnSbSe 3 system to increase the lattice thermal conductivity from 0.65 to 1.05 W m -1  K -1 by replacing 18% of the Sb sites with Cd. It is found that the presence of lone pair electrons leads to the off-centering of cations from the centrosymmetric position of a cubic lattice. X-ray pair distribution function analysis reveals that this structural distortion is relieved when the electronic configuration of the dopant element cannot produce lone pair electrons. Furthermore, a decrease in the Grüneisen parameter with doping is experimentally confirmed, establishing a relationship between the stereochemical activity of lone pair electrons and the lattice anharmonicity. The observed "harmonic" behavior with doping suggests that lone pair electrons must be preserved to effectively suppress phonon transport in these systems., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Dysregulation of the hypothalamic-pituitary-adrenal axis and abnormalities in the glucocorticoid receptor (GR) have been linked to major depressive disorder. Given the critical role of GR in stress response regulation, we investigated the impact of GR changes on neural stem cells (NSCs) proliferation and hippocampal neurogenesis. Stress response was induced using dexamethasone (DEX), a GR agonist, which led to reduced proliferation of neural stem cells and neural progenitor cells, as well as decreased expression of GR. Additionally, a reduction of serum concentration within the culture media resulted in suppressed cell proliferation, accompanied by decreased GR expression. The association between GR expression and cell proliferation was further confirmed through GR siRNA knockdown and overexpression experiments. Furthermore, in vivo studies utilizing young male C57BL/6 mice demonstrated that corticosterone (CORT) (35 μg/ml) administered through drinking water for four weeks induced depression-like behavior, as indicated by increased immobility times in forced swimming and tail suspension tests. CORT exposure led to reduced GR and nestin expression levels, along with diminished numbers of BrdU-positive cells in the hippocampi, indicating impaired hippocampal neurogenesis. Taken together, our findings provide the first evidence that stress-induced downregulation of GR negatively affects neurogenesis by inhibiting NSCs proliferation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Most reported thin-film piezoelectric energy harvesters have been based on cantilever-type crystalline ferroelectric oxide thin films deposited on rigid substrates, which utilize vibrational input sources. Herein, we introduce flexible amorphous thin-film energy harvesters based on perovskite CaCu 3 Ti 4 O 12 (CCTO) thin films on a plastic substrate for highly competitive electromechanical energy harvesting. The room-temperature sputtering of CCTO thin films enable the use of plastic substrates to secure reliable flexibility, which has not been available thus far. Surprisingly, the resultant amorphous nature of the films results in an output voltage and power density of ~38.7 V and ~2.8 × 10 6 μW cm -3 , respectively, which break the previously reported record for typical polycrystalline ferroelectric oxide thin-film cantilevers. The origin of this excellent electromechanical energy conversion is systematically explored as being related to the localized permanent dipoles of TiO 6 octahedra and lowered dielectric constant in the amorphous state, depending on the stoichiometry and defect states. This is the leading example of a high-performance flexible piezoelectric energy harvester based on perovskite oxides not requiring a complex process for transferring films onto a plastic substrate., (© 2024. The Author(s).)

Background: Health-adjusted life expectancy (HALE) is an indicator of the average lifespan in good health. Through this study, we aimed to identify regional disparities in the gap between HALE and life expectancy, considering the trends that have changed over time in Korea., Methods: We employed a group-based multi-trajectory modeling approach to capture trends in the gap between HALE and life expectancy at the regional level from 2008 to 2019. HALE was calculated using incidence-based "years lived with disability." This methodology was also employed in the Korean National Burden of Disease Study., Results: Based on five different information criteria, the most fitted number of trajectory groups was seven, with at least 11 regions in each group. Among the seven groups, one had an exceptionally large gap between HALE and life expectancy compared to that of the others. This group was assigned to 17 regions, of which six were metropolitan cities., Conclusion: Based on the results of this study, we identified regions in which health levels have deteriorated over time, particularly within specific areas of metropolitan cities. These findings can be used to design comprehensive policy interventions for community health promotion and urban regeneration projects in the future., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Diclofenac, a widely used non-steroidal anti-inflammatory drug, can cause liver damage via its metabolic activation by hepatic CYP450s and UGT2B7. Fasting can affect drug-induced liver injury by modulating the hepatic metabolism, but its influence on diclofenac hepatotoxicity is unknown. Thus, we investigated diclofenac-induced liver damage after fasting in mice, and the cellular events were examined. Male ICR mice fasted for 16 h showed the elevation of CYP3A11, but the decreases of UGT2B7, glutathione (GSH), and GSH S-transferase-μ/-π levels in the livers. Diclofenac (200 mg/kg) injection into the mice after 16-h fasting caused more significant liver damage compared to that in the diclofenac-treated fed mice, as shown by the higher serum ALT and AST activities. Diclofenac-promoted hepatic oxidative stress (oxidized proteins, 4-hydroxynonenal, and malondialdehyde), endoplasmic reticulum (ER) stress (BiP, ATF6, and CHOP), and apoptosis (cleaved caspase-3 and cleaved PARP) were enhanced by fasting. Autophagic degradation was inhibited in the diclofenac-treated fasting mice compared to that of the corresponding fed mice. The results suggest that fasting can make the liver more susceptible to diclofenac toxicity by lowering GSH-mediated detoxification; increased oxidative/ER stresses and apoptosis and suppressed autophagic degradation may be the cellular mechanisms of the aggravated diclofenac hepatotoxicity under fasting conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Early diagnosis of Alzheimer's disease is crucial to stall the deterioration of brain function, but conventional diagnostic methods require complicated analytical procedures or inflict acute pain on the patient. Then, label-free Surface-enhanced Raman spectroscopy (SERS) analysis of blood-based biomarkers is a convenient alternative to rapidly obtain spectral information from biofluids. However, despite the rapid acquisition of spectral information from biofluids, it is challenging to distinguish spectral features of biomarkers due to interference from biofluidic components. Here, we introduce a deep learning-assisted, SERS-based platform for separate analysis of blood-based amyloid β (1-42) and metabolites, enabling the diagnosis of Alzheimer's disease. SERS substrates consisting of Au nanowire arrays are fabricated and functionalized in two characteristic ways to compare the validity of different Alzheimer's disease biomarkers measured on our SERS system. The 6E10 antibody is immobilized for the capture of amyloid β (1-42) and analysis of its oligomerization process, while various self-assembled monolayers are attached for different dipole interactions with blood-based metabolites. Ultimately, SERS spectra of blood plasma of Alzheimer's disease patients and human controls are measured on the substrates and classified via advanced deep learning techniques that automatically extract informative features to learn generalizable representations. Accuracies up to 99.5% are achieved for metabolite-based analyses, which are verified with an explainable artificial intelligence technique that identifies key spectral features used for classification and for deducing significant biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to investigate the association between multimorbidity, which refers to the presence of two or more chronic diseases, and periodontal disease in Korean adults using national survey data., Methods: A total of 12,440 Korean adults aged ≥19 years were selected from the seventh Korea National Health and Nutrition Examination Survey (KNHANES). We investigated periodontal disease status based on various variables, including the gender, age, educational level, income level, smoking and alcohol drinking status, frequency of daily toothbrushing, and unmet dental treatment needs. Furthermore, periodontal status according to diagnosed chronic diseases, including hypertension, dyslipidaemia, stroke, myocardial infarction, angina pectoris, and diabetes, was investigated, and the association between multimorbidity and periodontal disease was analysed through multiple logistic regression using SAS 9.4., Results: According to the general characteristics of the study participants, the prevalence of periodontal disease was higher in males, smokers, older age, and lower educational and income levels (p < 0.001). Moreover, as the frequency of daily toothbrushing increased, the distribution of periodontal disease decreased (p < 0.001). The prevalence of periodontal disease was higher in those with chronic diseases than in those without chronic diseases and was statistically significantly higher as the number of diagnosed chronic diseases increased (p < 0.001). Additionally, an increase in the number of chronic diseases was observed to increase the prevalence and risk of periodontal disease., Conclusion: These results suggest that multimorbidity significantly affects the prevalence of periodontal disease., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. Here, we investigated the role of hepatic FGF23 in alcoholic liver disease (ALD) and delineated the underlying molecular mechanism. FGF23 expression was compared in livers from alcoholic hepatitis patients and healthy controls. The role of FGF23 was examined in hepatocyte-specific knock-out (LKO) mice of cannabinoid receptor type 1 (CB1R), estrogen related receptor γ (ERRγ), or FGF23. Animals were fed with an alcohol-containing liquid diet alone or in combination with ERRγ inverse agonist. FGF23 is mainly expressed in hepatocytes in the human liver, and it is upregulated in ALD patients. In mice, chronic alcohol feeding leads to liver damage and induced FGF23 in liver, but not in other organs. FGF23 is transcriptionally regulated by ERRγ in response to alcohol-mediated activation of the CB1R. Alcohol induced upregulation of hepatic FGF23 and plasma FGF23 levels is lost in ERRγ-LKO mice, and an inverse agonist mediated inhibition of ERRγ transactivation significantly improved alcoholic liver damage. Moreover, hepatic CYP2E1 induction in response to alcohol is FGF23 dependent. In line, FGF23-LKO mice display decreased hepatic CYP2E1 expression and improved ALD through reduced hepatocyte apoptosis and oxidative stress. We recognized CBIR-ERRγ-FGF23 axis in facilitating ALD pathology through hepatic CYP2E1 induction. Thus, we propose FGF23 as a potential therapeutic target to treat ALD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway. Notably, its active site contains a cysteine residue that is susceptible to oxidation by hydrogen peroxide (H 2 O 2 ). This oxidation inhibits the phosphatase function of PTEN, critically contributing to the activation of the PI3K/AKT pathway. Upon the stimulation of cell surface receptors, the activity of NADPH oxidase (NOX) generates a transient amount of H 2 O 2 , serving as a mediator in this pathway by oxidizing PTEN. The mechanism underlying this oxidation, occurring despite the presence of highly efficient and abundant cellular oxidant-protecting and reducing systems, continues to pose a perplexing conundrum. Here, we demonstrate that the presence of bicarbonate (HCO 3 - ) promoted the rate of H 2 O 2 -mediated PTEN oxidation, probably through the formation of peroxymonocarbonate (HCO 4 - ), and consequently potentiated the phosphorylation of AKT. Acetazolamide (ATZ), a carbonic anhydrase (CA) inhibitor, was shown to diminish the oxidation of PTEN. Thus, CA can also be considered as a modulator in this context. In essence, our findings consolidate the crucial role of HCO 3 - in the redox regulation of PTEN by H 2 O 2 , leading to the presumption that HCO 4 - is a signaling molecule during cellular physiological processes.

Physical fitness (PF) includes various factors that significantly impacts athletic performance. Analyzing PF is critical in developing customized training methods for athletes based on the sports in which they compete. Previous approaches to analyzing PF have relied on statistical or machine learning algorithms that focus on predicting athlete injury or performance. In this study, six machine learning algorithms were used to analyze the PF of 1,489 male adolescent athletes across five sports, including track & field, football, baseball, swimming, and badminton. Furthermore, the machine learning models were utilized to analyze the essential elements of PF using feature importance of XGBoost, and SHAP values. As a result, XGBoost represents the highest performance, with an average accuracy of 90.14, an area under the curve of 0.86, and F1-score of 0.87, demonstrating the similarity between the sports. Feature importance of XGBoost, and SHAP value provided a quantitative assessment of the relative importance of PF in sports by comparing two sports within each of the five sports. This analysis is expected to be useful in analyzing the essential PF elements of athletes in various sports and recommending personalized exercise methods accordingly., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer., Methods: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated., Results: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively., Conclusion: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control., (© 2024. Society of Surgical Oncology.)

Macrophage stimulating protein (MSP) is a multifunctional serum protein produced in the liver, belonging to the plasminogen-related kringle protein family. It exerts diverse biological functions by activating a transmembrane receptor protein-tyrosine kinase known as RON in humans and SKT in mice. MSP plays a pivotal role in innate immunity and is involved in various activities such as cell survival, migration, and phagocytosis. Elucidating the regulatory mechanisms governing MSP gene expression is of great importance. In this study, we comprehensively elucidate the molecular mechanism underlying hepatic MSP gene expression in response to alcoholism. Exposure to ethanol specifically upregulated the expression of ERRγ and MSP in the liver, while not in other organs. Liver-specific knockout of the cannabinoid receptor type 1 (CB1R), an upstream regulator of ERRγ, inhibited the alcohol-induced upregulation of MSP expression. Overexpression of ERRγ alone was sufficient to enhance MSP expression in hepatic cell lines and in mice. Conversely, knockdown of ERRγ in cell lines or liver-specific knockout of ERRγ in mice reversed ethanol-induced MSP gene expression. Promoter studies revealed the direct binding of ERRγ to the MSP gene promoter at the ERR response element (ERRE), resulting in the positive regulation of MSP gene expression in response to alcohol. This finding was further supported by ERRE-mutated MSP-luciferase reporter assays. Notably, treatment with GSK5182, an ERRγ-specific inverse agonist, significantly suppressed alcohol-induced hepatic MSP expression. Collectively, we exposed a novel mechanistic understanding of how alcohol-induced ERRγ controls the transcriptional regulation of MSP gene expression in the liver., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Modern semiconductor fabrication is challenged by difficulties in overcoming physical and chemical constraints. A major challenge is the wet etching of dummy gate silicon, which involves the removal of materials inside confined spaces of a few nanometers. These chemical processes are significantly different in the nanoscale and bulk. Previously, electrical double-layer formation, bubble entrapment, poor wettability, and insoluble intermediate precipitation have been proposed. However, the exact suppression mechanisms remain unclear due to the lack of direct observation methods. Herein, we investigate limiting factors for the etching kinetics of silicon with tetramethylammonium hydroxide at the nanoscale by using liquid-phase transmission electron microscopy, three-dimensional electron tomography, and first-principles calculations. We reveal suppressed chemical reactions, unstripping phenomena, and stochastic etching behaviors that have never been observed on a macroscopic scale. We expect that solutions can be suggested from this comprehensive insight into the scale-dependent limiting factors of fabrication.

With shrinking dimensions in integrated circuits, sensors, and functional devices, there is a pressing need to develop nanofabrication techniques with simultaneous control of morphology, microstructure, and material composition over wafer length scales. Current techniques are largely unable to meet all these conditions, suffering from poor control of morphology and defect structure or requiring extensive optimization or post-processing to achieve desired nanostructures. Recently, thermomechanical nanomolding (TMNM) has been shown to yield single-crystalline, high aspect ratio nanowires of metals, alloys, and intermetallics over wafer-scale distances. Here, TMNM is extended for wafer-scale fabrication of 2D nanostructures. Using In, Al, and Cu, nanomold nanoribbons with widths < 50 nm, depths ≈0.5-1 µm and lengths ≈7 mm into Si trenches at conditions compatible is successfully with back end of line processing . Through SEM cross-section imaging and 4D-STEM grain orientation maps, it is shown that the grain size of the bulk feedstock is transferred to the nanomolded structures up to and including single crystal Cu. Based on the retained microstructures of molded 2D Cu, the deformation mechanism during molding for 2D TMNM is discussed., (© 2023 Wiley‐VCH GmbH.)

Adipose tissue (AT) adapts to overnutrition in a complex process, wherein specialized immune cells remove and replace dysfunctional and stressed adipocytes with new fat cells. Among immune cells recruited to AT, lipid-associated macrophages (LAMs) have emerged as key players in obesity and in diseases involving lipid stress and inflammation. Here, we show that LAMs selectively express transmembrane 4 L six family member 19 (TM4SF19), a lysosomal protein that represses acidification through its interaction with Vacuolar-ATPase. Inactivation of TM4SF19 elevates lysosomal acidification and accelerates the clearance of dying/dead adipocytes in vitro and in vivo. TM4SF19 deletion reduces the LAM accumulation and increases the proportion of restorative macrophages in AT of male mice fed a high-fat diet. Importantly, male mice lacking TM4SF19 adapt to high-fat feeding through adipocyte hyperplasia, rather than hypertrophy. This adaptation significantly improves local and systemic insulin sensitivity, and energy expenditure, offering a potential avenue to combat obesity-related metabolic dysfunction., (© 2024. The Author(s).)

Objectives: We aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA)., Methods: Female patients with RA aged 20-50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs., Results: A total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs., Conclusion: Methotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy., Competing Interests: Competing interests: Y-KS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer and JW Pharmaceutical. DHY has received research grants from Celltrion, has served as an outside board of Celltrion and is on the speakers’ bureau of Celltrion and Celltrion Healthcare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lip canting, which is a noticeable factor in patients with facial asymmetry, can be influenced by the dentofacial skeleton. During orthognathic surgery, postoperative changes in facial soft tissue occur along the newly positioned hard tissue. Therefore, the evaluation of soft tissue before surgery is important. The purpose of this study was to investigate the skeletal factors that can affect lip canting by statistically comparing 2 facial horizontal planes using a three-dimensional reconstruction model. The findings of the present study showed a statistical correlation between lip canting and 3 skeletal factors: menton deviation, maxillary canting, and ramal length differences. Furthermore, a statistical correlation was identified between the Frankfort Horizontal plane and the intercanthal plane compared with the lip canting line. This result suggests that the intercanthal plane could be a standard horizontal plane in three-dimensional reconstruction model analysis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Aims: This study was conducted to develop a population pharmacokinetic (PK) model of methotrexate in Korean patients with haematologic malignancy, identify factors affecting methotrexate PK, and propose an optimal dosage regimen for the Korean population., Methods: Data were retrospectively collected from 188 patients with acute leukaemia or non-Hodgkin's lymphoma who were admitted to Severance Hospital during the period from November 2005 to January 2016. Using demographic factors and laboratory results as potential covariates for PK parameters, model development was performed using NONMEM and optimal dosing regimens were developed using the final PK model., Results: A two-compartment model incorporating body weight via allometry best described the data, yielding typical parameter values of 25.09 L for central volume of distribution ( V 1 ), 17.65 L for peripheral volume of distribution ( V 2 ), 12.89 L/h for clearance (CL) and 0.655 L/h for inter-compartmental clearance in a 50 kg patient. Covariate analyses showed that, at the weight of 50 kg, CL decreased by 0.11 L/h for each 1-year increase in age above 14 years old and decreased 0.8-fold when serum creatinine level doubled, indicating the importance of age-specific dose individualization in methotrexate treatment. Volume of distribution at steady state derived from PK parameters (=  V 1  +  V 2 ) was 0.85 L/kg, which was similar to those in the Western or Chinese populations. Optimal doses simulated from the final model successfully produced the PK measures close to the target chosen., Conclusions: The population PK model and optimal dosage regimens developed in this study can be used as a basis to achieve precision dosing in Korean patients with haematologic malignancy., (© 2023 British Pharmacological Society.)

Background: The measurement of health levels and monitoring of characteristics and trends among populations and subgroups are essential for informing evidence-based policy decisions. This study aimed to examine the burden of disease in Korea for both the total population and subgroups in 2020, as well as analyze changes in disease burden from 2008 to 2020., Methods: We employed the methodology developed in the Korean National Burden of Disease and Injuries Study to calculate disability-adjusted life years (DALYs) by sex, causes, region, and income level from 2008 to 2020. DALYs were derived by combining years of life lost and years lived with disability., Results: In 2020, the burden of disease for the Korean population was estimated to be 25,439 DALYs per 100,000 population, reflecting a 13.8% increase since 2008. The leading causes of DALYs were diabetes mellitus, followed by low back pain and ischemic stroke. A sex-specific gap reversal was observed, with the disease burden for men surpassing that of women starting in 2017. Furthermore, variations in disease burden were identified across 250 regions and income quintiles., Conclusion: It is imperative to establish appropriate health policies that prioritize the diseases with significantly increasing burdens and subgroups experiencing high disease burdens. The findings of this study are expected to serve as a foundation for developing healthcare policies aimed at improving the health levels of Koreans and achieving health equity., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Bone differentiation is crucial for skeletal development and maintenance. Its dysfunction can cause various pathological conditions such as rickets, osteoporosis, osteogenesis imperfecta, or Paget's disease. Although traditional two-dimensional cell culture systems have contributed significantly to our understanding of bone biology, they fail to replicate the intricate biotic environment of bone tissue. Three-dimensional (3D) spheroid cell cultures have gained widespread popularity for addressing bone defects. This review highlights the advantages of employing 3D culture systems to investigate bone differentiation. It highlights their capacity to mimic the complex in vivo environment and crucial cellular interactions pivotal to bone homeostasis. The exploration of 3D culture models in bone research offers enhanced physiological relevance, improved predictive capabilities, and reduced reliance on animal models, which have contributed to the advancement of safer and more effective strategies for drug development. Studies have highlighted the transformative potential of 3D culture systems for expanding our understanding of bone biology and developing targeted therapeutic interventions for bone-related disorders. This review explores how 3D culture systems have demonstrated promise in unraveling the intricate mechanisms governing bone homeostasis and responses to pharmacological agents.

The purpose of study was to evaluate that kallistatin deficiency causes excessive production of reactive oxygen species and exacerbates neuronal injury after cardiac arrest. For in vitro study, kallistatin knockdown human neuronal cells were given ischemia-reperfusion injury, and the oxidative stress and apoptosis were evaluated. For clinical study, cardiac arrest survivors admitted to the ICU were divided into the good (CPC 1-2) and poor (CPC 3-5) 6-month neurological outcome groups. The serum level of kallistatin, Nox-1, H 2 O 2 were measured. Nox-1 and H 2 O 2 levels were increased in the kallistatin knockdown human neuronal cells with ischemia-reperfusion injury (p < 0.001) and caspase-3 was elevated and apoptosis was promoted (SERPINA4 siRNA: p < 0.01). Among a total of 62 cardiac arrest survivors (16 good, 46 poor), serum kallistatin were lower, and Nox-1 were higher in the poor neurological group at all time points after admission to the ICU (p = 0.013 at admission; p = 0.020 at 24 h; p = 0.011 at 72 h). At 72 h, H 2 O 2 were higher in the poor neurological group (p = 0.038). Kallistatin deficiency exacerbates neuronal ischemia-reperfusion injury and low serum kallistatin levels were associated with poor neurological outcomes in cardiac arrest survivors., (© 2024. The Author(s).)

Background: Healthy life expectancy is a well-recognized indicator for establishing health policy goals used in Korea's Health Plan. This study aimed to explore Koreans' healthy life expectancy and its gender, income, and regional disparities from 2008 to 2020., Methods: This study was conducted on the entire population covered by health insurance and medical aid program in Korea. The incidence-based "years lived with disability" for 260 disease groups by gender, income level, and region was calculated employing the methodology developed in the Korean National Burden of Disease Study, and it was used as the number of healthy years lost to calculate health-adjusted life expectancy (HALE)., Results: Koreans' HALE increased from 68.89 years in 2008 to 71.82 years in 2020. Although the gender disparity in HALE had been decreasing, it increased to 4.55 years in 2020. As of 2020, 5.90 years out of 8.67 years of the income disparity (Q5-Q1) in HALE were due to the disparity between Q1 and Q2, the low-income groups. Income and regional disparities in HALE exhibited an increasing trend, and these disparities were higher in men than in women., Conclusion: A subgroup with a low health level was identified through the HALE results, and it was confirmed that improving the health level of this population can reduce health inequalities and improve health at the national level. Further exploration of the HALE calculation methodology may help in the development of effective policies such as prioritizing interventions for health risk factors., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth, and proliferation by downregulating the PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury, and immune responsiveness. Therefore, recently, PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H 2 O 2 ), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Herein, we provide an overview of studies that highlight the role of the oxidative inhibition of PTEN in physiological processes.

Background: Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ., Methods: This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant., Results: The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72-90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ., Conclusions: Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ., (© 2024. The Author(s).)

Background: It has often been reported that thyroid-specific autoimmune diseases (ADs), such as Hashimoto's thyroiditis and Graves' disease, could increase the risk of thyroid cancer, but the association between other ADs beyond thyroid and thyroid cancer has not been well investigated. This study aimed to examine the risk of thyroid cancer in patients with eight ADs compared with those without ADs. Methods: This nationwide retrospective matched cohort study was conducted to investigate the relationship of eight ADs (Hashimoto's thyroiditis, Graves' disease, type 1 diabetes mellitus, Sjogren's disease, inflammatory bowel disease [IBD], vitiligo, systemic lupus erythematosus, and rheumatoid arthritis [RA]) with the risk of incident thyroid cancer using the National Health Insurance Service-National Sample Cohort. The Cox-proportional hazard model was used to estimate the adjusted hazard ratio (HR) and confidence intervals (CI) for thyroid cancer in relation to each of AD compared with control group without AD. Results: During the average follow-up of 9.49 years, 138 thyroid cancer cases were newly developed in control group and 268 cases were occurred in group with 8 ADs. For all of study participants, the risk of thyroid cancer was significantly increased in patients with Hashimoto's thyroiditis (HR = 2.10 [1.57-2.81]), Graves' disease (HR = 2.67 [1.99-3.62]), IBD (HR = 2.06 [1.50-2.83]), vitiligo (HR = 1.71 [1.13-2.59]), RA (HR = 1.76 [1.07-2.90]), and total of 8 ADs (HR = 1.97 [1.60-2.42]) compared with control group without ADs. When ADs were divided into three types, thyroid-specific ADs (HR = 2.37 [1.85-3.03]) showed the strongest and significant association with thyroid cancer, followed by local ADs (HR = 1.83 [1.41-2.38]), and systemic ADs (HR = 1.77 [1.14-2.74]). Conclusions: Specific ADs-especially for thyroid-specific AD, vitiligo, IBD, and RA-were associated with increased risk for thyroid cancer.

Parkinson's disease (PD) is a neurodegenerative disorder that results in motor impairment due to dopaminergic neuronal loss. The pathology of PD is closely associated with neuroinflammation, which can be characterized by astrocyte activation. Thus, targeting the inflammatory response in astrocytes might provide a novel therapeutic approach. We conducted a luciferase assay on an in-house chemical library to identify compounds with anti-inflammatory effects capable of reducing MPP + -induced NF-κB activity in astrocytes. Among the compounds identified, EI-16004, a novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides, exhibited a significant anti-inflammatory effect by significantly reducing MPP + -induced astrocyte activation. Biochemical analysis and docking simulation indicated that EI-16004 inhibited the MPP + -induced phosphorylation of p65 by attenuating ERK phosphorylation, and EI-16004 reduced pro-inflammatory cytokine and chemokine levels in astrocytes. In vivo studies on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in male C57BL/6 mice showed that EI-16004 ameliorated motor impairment and protected against dopaminergic neuronal loss, and EI-16004 effectively mitigated the MPTP-induced astrocyte activation in striatum (STR) and substantia nigra (SN). These results indicate EI-16004 is a potential neuroprotective agent for the prevention and treatment of astrocyte-mediated neuroinflammatory conditions in PD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)