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Objective: Previous studies have reported that vitamin D deficiency increased the risk of Alzheimer's disease (AD) dementia in older adults. However, little is known about how vitamin D is involved in the pathophysiology of AD. Thus, this study aimed to examine the association and interaction of serum vitamin D levels with in vivo AD pathologies including cerebral beta-amyloid (Aβ) deposition and neurodegeneration in nondemented older adults., Methods: 428 Nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25-hydroxyvitamin D (25[OH]D), and multimodal brain imaging including Pittsburgh compound B (PiB) positron emission tomography and magnetic resonance imaging. Global PiB deposition was measured for the Aβ biomarker. Intracranial volume-adjusted hippocampal volume (HVa) was used as a neurodegeneration biomarker., Results: Overall, serum 25(OH)D level was not associated with either Aβ deposition or HVa after controlling for age, sex, apolipoprotein E ε4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderating effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (B = 34.612, p = 0.008)., Conclusion: Our findings indicate that lower serum vitamin D levels may contribute to AD by exacerbating Aβ-associated neurodegeneration in nondemented older adults. Further studies to explore the potential therapeutic effect of vitamin D supplementation on the progression of AD pathology will be necessary.

Objective: We intended to investigate the relationships between visual sensory impairment (VSI) or auditory sensory impairment (ASI) and brain pathological changes associated with cognitive decline in older adults., Methods: We primarily tried to examine whether each sensory impairment is related to Alzheimer's disease (AD) pathology, specifically beta-amyloid (Aβ) deposition, through both cross-sectional and longitudinal approaches in cognitively unimpaired older adults. Self-report questionnaires on vision and hearing status were administered at the baseline. Neuroimaging scans including brain [ 11 C] Pittsburgh Compound B PET and MRI, as well as clinical assessments, were performed at baseline and 2-year follow-up., Results: Cross-sectional analyses showed that the VSI-positive group had significantly higher Aβ deposition than the VSI-negative group, whereas there was no significant association between ASI positivity and Aβ deposition. Longitudinal analyses revealed that VSI positivity at baseline was significantly associated with increased Aβ deposition over 2 years (β = 0.153, p = 0.025), although ASI positivity was not (β = 0.045, p = 0.518). VSI positivity at baseline was also significantly associated with greater atrophic changes in AD-related brain regions over the 2-year follow-up period (β = -0.207, p = 0.005), whereas ASI positivity was not (β = 0.024, p = 0.753). Neither VSI nor ASI positivity was related to cerebrovascular injury, as measured based on the white matter hyperintensity volume., Conclusion: The findings suggest that VSI is probably related to AD-specific pathological changes, which possibly mediate the reported relationship between VSI and cognitive decline. In contrast, ASI appears not associated with AD pathologies but may contribute to cognitive decline via other mechanisms.

Purpose: Microfocused ultrasound with real-time visualization (MFU-V) is often used for noninvasive skin lifting, by precisely targeting dermal and subcutaneous tissues to create thermal coagulation points (TCPs). These TCPs denature collagen and initiate a transient inflammatory response, ultimately attracting dermal fibroblasts and inducing efficient neocollagenesis and extracellular matrix (ECM) remodeling, yielding to MFU-V's desired skin-lifting effects. The current study investigates MFU-V's underlying mode of action based on the histological progression of TCPs in the skin, providing new insight into the technology's regenerative effect., Methods: Following standard triple-depth MFU-V treatment, in vivo skin samples were assessed using histology and immunohistochemistry to evaluate TCPs, heat shock protein (HSP47), and elastin expression in fibroblasts., Results: MFU-V treatment induced elongated, flame-like TCPs with denatured collagen at focal depths of 1.5, 3.0, and 4.5 mm within the skin-each corresponding to its respective transducer depth. Time-dependent progression of TCPs showed significantly increased scores of fibroblasts and mature collagen along with recruitment of HSP47-positive fibroblasts to TCP areas on Day 90. Collagen formation and later maturation were visualized. Newly synthesized elastin significantly increased in the TCP area on Day 90 compared to Day 14., Conclusion: This work provides histological evidence of stimulation and regeneration of newly synthesized elastin fibers after TCP induction. MFU-V-generated TCPs triggered the body's own healing cascade of collagen denaturation, transient inflammation, proliferation, and tissue remodeling, resulting in attraction of HSP47-positive fibroblasts to the TCP sites, and new collagen and elastin fiber regeneration by fibroblasts. Besides the well-described neocollagenesis, this study demonstrates that MFU-V treatment induces elastin neogenesis that may result not only in skin lifting but also in improved skin elasticity, providing an overall regenerative effect., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Nucleic acid detection is important in a wide range of applications, including disease diagnosis, genetic testing, biotechnological research, environmental monitoring, and forensic science. However, the application of nucleic acid detection in various fields is hindered by the lack of sensitive, accurate, and inexpensive methods. This study introduces a simple approach to enhance the sensitivity for the accurate detection of nucleic acids. Our approach combined a split-probe strategy with in vitro translational amplification of reporter protein for signal generation to detect nucleic acids with high sensitivity and selectivity. This approach enables target-mediated translational amplification of reporter proteins by linking split probes in the presence of a target microRNA (miRNA). In particular, the fluorescence split-probe sensor adopts a reporter protein with various fluorescence wavelength regions, enabling the simultaneous detection of multiple target miRNAs. Moreover, luminescence detection by merely altering the reporter protein sequence can substantially enhance the sensitivity of detection of target miRNAs. Using this system, we analyzed and quantified target miRNAs in the total RNA extracted from cell lines and cell-derived extracellular vesicles with high specificity and accuracy. This split-probe sensor has potential as a powerful tool for the simple, sensitive, and specific detection of various target nucleic acids.

Background: Evidence has indicated that nocturia is a clinical manifestation of adverse health conditions, including cardiovascular diseases and metabolic disorders. However, previous studies are less available for the clinical implication of nocturia on the development of hypertension., Methods: Study participants were 32,420 working-aged Koreans (21,355 men and 11,065 women) who periodically received health checkups. They were categorized into 4 groups by the frequency of nocturia (never, <1, 1-2, and ≥3/week). We used Cox proportional hazards models to analyze the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CIs) for incident hypertension (multivariable-adjusted HR [95% CI]) in relation to the frequency of nocturia. Subgroup analysis was conducted by gender and sleep quality (good and poor sleep quality)., Results: In women, nocturia was associated with an increased risk of hypertension, compared with never nocturia (HR [95% CI]; never: reference, <1/week: 1.33 [1.10-1.60], 1-2/week: 1.26 [1.00-1.58], and ≥3/week: 1.34 [1.05-1.72]). This association was not observed in men (HR [95% CI]; never: reference, <1/week: 1.00 [0.93-1.08], 1-2/week: 1.00 [0.88-1.12], and ≥3/week: 1.06 [0.94-1.23]). In subgroup analysis by sleep quality, only women with good sleep quality showed an association between nocturia and the risk of hypertension. However, women with poor sleep quality and men did not show an association between the frequency of nocturia and the risk of hypertension., Conclusions: Nocturia is a potential risk factor for incident hypertension in working-aged women with good sleep quality., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background/aims: : The relationship between genetic polymorphisms and gastric inflammation remains unclear. This study aimed to evaluate the impact of genetic polymorphisms on Helicobacter pylori (HP)-associated gastritis according to sex., Methods: : Two hundred thirty-two male and 404 female subjects with current HP infection were prospectively enrolled. The genotyping of IL-1B-511 C/T, IL-1RN variable number of tandem repeats, IL-6-572 G/C, IL-8-251 A/T, IL-8-781 C/T, IL-10-1082 G/A, IL-10-592 C/A, TNF-A-308 G/A, and transforming growth factor ( TGF )- B-509 C/T, was determined by polymerase chain reaction-restriction fragment length polymorphism. The degree of monocyte or neutrophil infiltration, atrophic gastritis, and intestinal metaplasia was evaluated using the updated Sydney system., Results: : Among the male subjects, moderate/severe atrophic gastritis of the corpus was higher in IL-1B-511 CC carriers than in CT and TT carriers independent of age, alcohol consumption, and HP virulence factors (26.9% vs 10.4%; adjusted hazard ratio [HR], 4.377; 95% confidence interval, 1.387 to 13.814). In females, IL-8-251 AA carriers were independently and significantly associated with moderate/severe atrophic gastritis of the corpus compared with that in AT and TT carriers (21.4% vs 6.0%, adjusted HR=3.799). In males, the IL-8-251 TT genotype was associated with moderate/severe intestinal metaplasia of the corpus compared with the AT and AA genotypes (13.4% vs 5.6%, adjusted HR=3.128), while the IL-10-592 CA and CC genotypes were associated with moderate/severe monocyte infiltration of the antrum compared with AA genotype (83.6% vs 71.8%, adjusted HR=2.227)., Conclusions: : Genetic polymorphisms in cytokines play different roles in HP-associated gastritis according to sex.

Food waste (FW) comprises carbohydrates, proteins, lipids, and water, posing technical challenges for effective treatment and valorisation. This study addresses these challenges by using black soldier fly larvae (BSFL) as a bioconversion medium to transform FW into biodiesel (BD). BSFL predominantly consumed the carbohydrates and proteins in FW (81 wt%), while showing a lower preference for lipids (<50 wt% consumed). Notwithstanding the lower consumption of lipids in the FW than that of carbohydrates and proteins, BSFL had a high lipid content (48.3 wt%). The subsequent conversion of the lipids extracted from BSFL into BD was tested via catalytic (acid/alkali) and non-catalytic transesterification processes. The BD yield from catalytic transesterification was lower than that from non-catalytic transesterification because of the low tolerance against free fatty acids (FFAs). BD was also produced from the lipid-concentrated residual FW through non-catalytic transesterification. Although the FW residue extracts contained high amounts of FFAs (49.9 wt%), non-catalytic transesterification displayed a high BD yield (92.4 wt%; yields from catalytic transesterification: < 80.0 wt%). Moreover, blending the BD derived from the BSFL and FW residue extracts enhanced the fuel properties. The BSFL-assisted FW management efficiently reduced FW by 90 wt% while producing a high-quality BD., 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.)

Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future., 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.)

Background/aims: : Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them., Methods: : We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness., Results: : Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4., Conclusions: : Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

Perceived temperature (PT), which encompasses meteorological factors such as wind speed, cloud cover, and humidity, reflects the actual effect of temperature on the human body. However, limited data exist on the health implications of prolonged exposure to low temperatures during winter in individuals with chronic kidney disease (CKD). We investigated the association between winter PT and long-term outcomes among CKD patients. A total of 32,870 CKD patients from three tertiary hospitals in Seoul were enrolled in this retrospective study (2001-2018). PT was calculated using Staiger's equation, integrating temperature data from 29 automated weather stations across Seoul, along with dew point temperature, wind velocity, and cloud cover data. Kriging interpolation was utilized to estimate PT values at the patients' locations. Overall mortality and major adverse cardiovascular events (MACEs) were assessed using a time-varying Cox proportional hazards model. Additionally, the Cox regression model evaluated PT corresponding to temperature thresholds for cold surge watches or warnings. Over a median follow-up of 6.14 ± 3.96 years, 6147 deaths (18.7%) were recorded. We found that as the average or minimum PT and Ta decreased by 1 °C, the risk of overall mortality significantly increased. In multivariable analyses, the hazard ratio (HR) for the average PT was 1.049 (95% confidence interval [CI] 1.028-1.071), and that for the minimum PT was 1.038 (CI 1.027-1.052). Furthermore, a cold surge warning at a PT of -25.63 °C indicated an HR of 1.837 (CI 1.764-1.914) and a C-index of 0.792. The increased risk of mortality was more pronounced in patients with low or middle socioeconomic statuses. For MACEs, lower average and minimum PT and Ta were associated with an increased risk, following a similar trend to overall mortality, although not all results reached statistical significance. These findings emphasize the importance of targeted public health policies to mitigate risks among vulnerable CKD patients., 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 Inc.)

This study aimed to investigate the characteristics of out-of-office blood pressure (BP) measurements in patients with apparent treatment-resistant hypertension (aRH) enrolled from 15 tertiary care centers in South Korea. aRH was defined as having uncontrolled office BP ≥ 130/80 mmHg despite receiving three classes of antihypertensive medication or any level of BP despite receiving ≥4 classes of antihypertensive medication. Patients with complete data for office BP, 24-h ambulatory BP monitoring (ABPM), and home BP measurements at baseline were included. BP control status between ABPM and home BP measurements was compared. Out of 1457 patients, 823 meeting the enrollment criteria were included (mean age: 59.9 ± 13.6 years; 57.5% male patients). Among them, 7.2% had controlled BP, 8.7% had whitecoat uncontrolled hypertension, 15.1% had masked uncontrolled hypertension, and 69% had sustained hypertension, as measured through baseline ABPM. Additionally, 43% of patients with controlled BP based on home BP measurement had nocturnal hypertension. Relying solely on home BP measurement may result in misclassifying 70% of patients as having either controlled BP or whitecoat uncontrolled BP. This study reaffirms the circadian pattern of resistant hypertension, characterized by a higher prevalence of non-dipping and rising patterns, even in patients with BP controlled based on ABPM. Considering the persistent difference between home BP measurement and ABPM, even at a lower home BP threshold, integrating both measurements into the management of aRH is advisable., Competing Interests: Compliance with ethical standards Conflict of interest JS have nothing to declare. CJL received lecture honoraria from Novartis, Hanmi Pharmaceutical, Yuhan, Boryung Pharmaceutical, and Daiichi Sankyo. DHK received honoraria from Viatris, Organon, Boryoung, Hanmi, Daewoong, Celltrion, Daiichi Sankyo, and Chong Kun Dang and a research grant from Daewoong Pharmaceutical. SYK received honoraria from Norvatis, Amgen Korea, BMS Korea, Bayer Korea, Viatris, Boryoung, Hanmi, Menarini, JW Pharmaceutical, Inno N, Dongkook, Yuhan, Chong Kun Dang, GC Biopharma, and Daewon. JHP received honoraria from Viatris, Jeil, Boryoung, Daewoong, Hanmi, Yuhan, Chong Kun Dang, BMS. ICK received honoraria from Abbott, Novartis, Yuhan, Viatris, Organon, Boryoung, Hanmi, Daewoong, Celltrion, Servier, Daiichi Sankyo, Chong Kun Dang, and Daewon. JHL received honoraria from Daewoong Pharmaceutical, Handok Pharmaceuticals, Novartis, Chong Kun Dang Pharmaceutical Corp, Menarini Korea, Samjin Pharmaceuticals Co. Ltd, Daiichi Sankyo Korea, Hanmi Pharmaceutical, Yuhan Corporation, Boryung Pharmaceutical, Bayer. HYL received honoraria from Viatris, Organon, Boryoung, Hanmi, Daewoong, Donga, Celltrion, Servier, Daiichi Sankyo, Chong Kun Dang, and Daewon, and a research grant from Daiichi Sankyo. HYL also received consultation fee from Skylab. JWC received honoraria from Bayer, Astrazeneca, Organon, Hanmi, Yuhan, Daewoong, Chong Kun Dang, JW, Boryoung, GC Corp, Donga, Handok, Ildong, Jeil, Daewon, Ahn-gook, Samjin, Daiichi Sankyo, Otsuka, Mitsubishi Tanabe, Hyundai, Kuhnil, Bukwang and Aju. JWC also received research grants from Handok, Daewon, Boryung, GC Corp, Addpharma, and Kyung Dong. SHI received honoraria from Boryoung, Daewoong, Donga, Celltrion, Servier, Daiichi Sankyo, and Menarini, and a research grant from Daiichi Sankyo. SHI has received consultation fee from Skylab. JS received honoraria from Boryoung, Daiichi Sankyo, Chong Kun Dang, and Inno-N and consultaion fee from Skylab and Inbody. SP received honoraria from Viatris, Organon, Boryoung, Hanmi, Daewoong, Donga, Celltrion, Servier, Daiichi Sankyo, Chong Kun Dang, and Daewon, and a research grant from Daiichi Sankyo. SP has received consultation fee from Skylab. Also, SP has received stock option from Mediwhale. Others have nothing to declare., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE -/- mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

RIPK1/RIPK3-MLKL signaling molecules are fundamental in initiating necroptotic cell death, but their roles in the development of colon cancer are unclear. This study reports that RIPK3 interacted with SPOP, a component of the E3 ligase within the Cul3 complex. This interaction leads to K48-linked ubiquitination and subsequent proteasomal degradation of RIPK3. Two distinct degron motifs, PETST and SPTST, were identified within the linker domain of RIPK3 for SPOP. RIPK3 phosphorylations at Thr403 by PIM2 and at Thr412/Ser413 by ERK2 are essential to facilitate its interaction with SPOP. Computational docking studies and immunoprecipitation analyses showed that these PIM2 and ERK2 phosphorylations bolster the stability of the RIPK3-SPOP interaction. In particular, mutations of RIPK3 at the degron motifs extended the half-life of RIPK3 by preventing its phosphorylation and subsequent ubiquitination. The deletion of SPOP, which led to increased stability of the RIPK3 protein, intensified LPS/sMAC/zVAD-induced necroptotic cell death in colon cancer cells. These findings underscore the critical role of the SPOP-mediated RIPK3 stability regulation pathway in controlling necroptotic cell death., Competing Interests: Declarations Consent for publication All authors read and approved the submission and final publication. Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

In this study, we developed two plasmid constructs, pJHL270 and pJHL305, for the dual expression of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Gn and Gc glycoproteins in both prokaryotic and eukaryotic systems. The constructs feature a prokaryotic expression controlled by the Ptrc promoter and a eukaryotic expression driven by the cytomegalovirus promoter and Semliki Forest Virus RNA-dependent RNA polymerase. The Gn/Gc antigenic epitope was derived from consensus sequences of 12 SFTSV M segments collected in South Korea and designed for optimal antigen expression. The full antigen was expressed eukaryotically for post-translational modifications, while the epitope construct was expressed prokaryotically. These constructs were electroporated into an attenuated Salmonella Typhimurium strain (JOL2500) for plasmid delivery, resulting in JOL3042 and JOL3045. Successful expression was confirmed via qRT-PCR and western blot analysis. Mice immunized with JOL3042 showed antibody responses as early as two weeks, while JOL3045 elicited responses at six weeks, skewed toward a Th1 response initially, later balancing with Th2. Flow cytometry revealed significant CD3 + CD4 + and CD3 + CD8 + T-cell responses. Both constructs generated neutralizing antibodies, and a challenge study indicated significant reductions in viral loads in the serum, liver, and spleen of vaccinated mice, demonstrating the effectiveness of the Salmonella-mediated delivery system against SFTSV infection. The outcome of the current study may pave the way to develop a safer and more effective Salmonella-mediated vaccine against lethal SFTSV infection in vulnerable populations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John Hwa Lee reports financial support was provided by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1A6A1A03033084 and 2022R1A6A3A01086797). John Hwa Lee reports a relationship with Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education that includes: funding grants. If there are other authors, they 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.)

In this study, we investigate the atomic layer deposition (ALD) process on all-inorganic CsPbBr 3 perovskite nanocrystals (PNCs) to introduce an inorganic electron transport layer (ETL) in light-emitting diode (LED) devices. Two types of CsPbBr 3 PNCs were synthesized with oleate (OA) and oleylammonium (OLA) ligands on the surface. We found that CsPbBr 3 PNCs with Cs oleate surfaces experienced severe photoluminescence (PL) quenching after the ALD process, while those with oleylammonium bromide surfaces did not show any significant PL drop. Transmission electron microscopy and X-ray photoelectron spectroscopy revealed that significant Pb metal formation and Ruddlesden-Popper planar faults, linked to uncoordinated Pb 2+ ion defects, were generated in CsPbBr 3 PNCs terminated with Cs oleate after ALD ZnO. Finally, we fabricated LEDs using PNCs with an ALD ZnO process to introduce inorganic ZnMgO nanoparticles as the ETL. The devices processed with ALD exhibited superior luminance and external quantum efficiency compared to those without the ALD process. This research provides crucial insights into the surface-dependent chemistry of PNCs and the surface-dependent performance of perovskite-based optoelectronic devices.

Diabetic retinopathy is a disease that can cause vision loss leading to blindness in people with diabetes. Improved methods to treat and prevent vision loss in diabetic patients are in high demand owing to limited current treatment procedures. Herein, we report a new class of transglutaminase 2 (TGase2) inhibitors for the treatment of diabetic retinopathy based on 7-aminoquinoline-5,8-dione derivatives. 7-Amino-2-phenylquinoline-5,8-dione 11 and 7-amino-2-{4-[(1-methylpiperidin-4-yl)oxy]phenyl}quinoline-5,8-dione 23 exhibited potent inhibitory activities against TGase2 in a fibrinogen array-based on-chip TGase2 activity assay and in an in situ assay in human retinal microvascular endothelial cells, with IC 50 values of 5.88 and 1.12 μM in vitro, and 0.09 and 0.07 μM in situ, respectively. Pharmacokinetically favorable 7-amino-2-{4-[(1-isopropylpiperidin-4-yl)oxy] phenyl}quinoline-5,8-dione 22 inhibited vascular leakage in the retinas of streptozotocin-induced diabetic mice via oral administration. Results from the AL5 kinetic assay and a molecular docking study suggest that the inhibitors may bind to TGase2 remote from the active site.

Due to the higher risk of medical complications posed by influenza infection, patients with type 1 diabetes (T1D) are strongly recommended to receive the influenza vaccine. However, it remains unclear if hyperglycemia in patients with T1D affects vaccine-induced immune responses. In this study, we investigated the humoral and cellular immune responses of prediabetic and diabetic, nonobese diabetic (NOD) mice following influenza vaccination to determine the effects of hyperglycemia on influenza vaccine-induced responses. In diabetic NOD mice, vaccine-specific IgG and IgM levels, as well as IgG-producing cells, were comparable to those in prediabetic NOD mice. However, the diabetic NOD mice exhibited reduced percentages of memory T cells and activated T cells in the spleen, along with reduced number of vaccine-specific interferon (IFN)-γ-secreting cells. Thus, these findings suggest that in patients with T1D, hyperglycemia could lead to impaired cell-mediated immune responses following influenza vaccination., 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.)

Autophagy is a crucial intracellular degradation process that provides energy and supports nutrient deprivation adaptation. However, the mechanisms by which these cells detect lipid scarcity and regulate autophagy are poorly understood. In this study, we demonstrate that protein kinase A (PKA)-dependent lipolysis delays autophagy initiation during short-term nutrient deprivation by inhibiting AMP-activated protein kinase (AMPK). Using coherent anti-Stokes Raman spectroscopy, we visualized free fatty acids (FFAs) in vivo and observed that lipolysis-derived FFAs were used before the onset of autophagy. Our data suggest that autophagy is triggered when the supply of FFAs is insufficient to meet energy demands. Furthermore, PKA activation promotes lipolysis and suppresses AMPK-driven autophagy during early fasting. Disruption of this regulatory axis impairs motility and reduces the lifespan of Caenorhabditis elegans during fasting. These findings establish PKA as a critical regulator of catabolic pathways, prioritizing lipolysis over autophagy by modulating AMPK activity to prevent premature autophagic degradation during transient nutrient deprivation., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Background: An understanding of the phenotypes and endotypes of atopic dermatitis (AD) is essential for developing precision therapies. Recent studies have demonstrated evidence for the gut-skin axis in AD., Objective: To determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms based on multi-omics analyses., Methods: Latent class trajectory analysis was used to AD phenotype in 2247 children who were followed until 9 years of age from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) birth cohort study. Multi-omics analyses (microbiome, metabolites, and gut epithelial cell transcriptome) using stool samples collected at 6 months of age were performed to elucidate the underlying mechanisms of AD phenotypes., Results: Five AD phenotypes were classified as follows: never/infrequent, early-onset transient, intermediate-transient, late-onset, and early-onset persistent. Early-onset persistent and late-onset phenotypes showed increased risks of food allergy and wheezing treatment ever, with bronchial hyperresponsiveness only evident in the early-onset persistent phenotype. Multi-omics analyses revealed a significantly lower relative abundance of Ruminococcus gnavus and a decreased gut acetate level in the early-onset persistent phenotype, with potential associations to ACSS2, JAK-STAT signaling, and systemic Th2 inflammation. The early-onset transient phenotype was associated with AMPK and/or chemokine signaling regulation, whereas the late-onset phenotype was linked with IL-17 and barrier dysfunction., Conclusions: Multi-omics profiling in early life may offer insights into different mechanisms underlying AD phenotypes in children., (Copyright © 2024. Published by Elsevier Inc.)

Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here, we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis. Splenic injection of Dkk2 knockout (KO) cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases. Transcriptome analysis showed reduction of Paneth cell markers such as lysozymes in KO organoids. Single-cell RNA sequencing analyses of murine metastasized colon cancer cells and patient samples identified the presence of lysozyme positive cells with Paneth cell properties including enhanced glycolysis. Further analyses of transcriptome and chromatin accessibility suggested hepatocyte nuclear factor 4 alpha (HNF4A) as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing analysis revealed that HNF4A binds to the promoter region of Sox9 , a well-known transcription factor for Paneth cell differentiation. In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers., Competing Interests: JS, JP, JL, JJ, RD, SM, JK, SP, JH, JW, AB No competing interests declared, JC Reviewing editor, eLife, (© 2024, Shin, Park et al.)

Fine inhalable particulate matter (PM 2.5 ) is a harmful airborne pollutant, with serious repercussions to public health worldwide. To prevent the influx of PM 2.5 into the indoor living and working space, we conceived the design of a "filtration window" that exhibits efficient PM 2.5 filtration capabilities while having sufficient transparency and physical durability. In this work, we demonstrate the successful fabrication of a transparent (∼80%) PM 2.5 filter based on nanofibrous poly(vinylidenefluoride- co -trifluoroethylene) (PVDF-TrFE), which captures PM 2.5 by electrostatic mechanisms originating from the ferroelectric property of the copolymer. The embedded PVDF-TrFE-based nanofibrous filter exhibits a notable PM 2.5 removal efficiency of 93%, which is on par with those of medical-grade face masks. Simultaneously, owing to its dense packing, the PVDF-TrFE nanofibrous filter is highly durable, allowing it to be cleaned with water for reuse, and withstands its structural integrity even under a wind flow of 15 m/s, altogether making it practically viable as a functional window unit.

The presence of oxygen vacancies (V o ) in electrocatalysts plays a significant role in improving the selectivity and activity of CO 2 reduction reaction (CO 2 RR). In this study, 1D material with large surface area is utilized to enable uniform V o formation on the catalyst. 1D structured indium selenoiodide (InSeI) is synthesized and used as an electrocatalyst for the conversion of CO 2 to formate. The electrochemical treatment of InSeI leads to the leaching of Se and I from the catalyst surface and the formation of V o . The resulting V o promotes the activity of the CO 2 RR, which increases the local pH of the catalyst surface and chemically maintains the oxidized metal sites on the catalyst. Owing to these characteristics, activated In wire exhibited remarkable CO 2 RR activity, thereby surpassing 93% FE formate at 500 mA cm -2 , with a maximum of 97.3% FE formate at 100 mA cm -2 . Moreover, the catalytic activity remained consistent for over 50 h at 100 mA cm -2 (FE formate >88%). Thus, the findings imply that using 1D materials can facilitate the formation of oxygen vacancies on the catalyst surface and improve the selectivity and durability of CO 2 RR. This indicates the potential for further research on 1D materials as electrocatalysts., (© 2024 Wiley‐VCH GmbH.)

Despite significant advancements in all-solid-state batteries (ASSBs), the reliance on thick solid electrolyte (SE) membranes hinders their commercial viability. Although the dry process using polytetrafluoroethylene (PTFE) binder is proposed for thin SE membranes, a comprehensive understanding of the correlation between PTFE fibrillation and SE membrane quality remains lacking. Here an important guidance is provided for producing durable SE membranes that can be reduced to sub-20-µm thickness by regulating the entanglement networks of PTFE. While establishing fabrication parameters; shear time and shear temperature, a dominant effect of the number-average molecular weight (M n ) on PTFE fibrillation is revealed for the first time. Moreover, the degree of PTFE fibrillation is quantified using systematic X-ray diffraction (XRD) analysis. The SE membrane utilizing the high-M n PTFE binder that achieves a maximum fibrillation degree (≈98%) and thus forms highly entangled fibrous PTFE network interweaving SE particles, exhibited superior toughness. Consequently, the 18 µm thick SE membrane with 0.5 wt% high-M n PTFE shows a considerably higher areal conductance. The ASSB using this durable, ultrathin SE membrane outperforms its counterparts that used flimsy SE membranes or pure SE pellets. Finally, uniquely thin ASSBs demonstrate significantly improved cell-level energy densities, showcasing the promising potential for practical ASSB fabrication., (© 2024 Wiley‐VCH GmbH.)

Keratin 17 (K17) is frequently overexpressed, associated with poor prognosis in various cancers, and contributes to p27 degradation during cancer progression. Using immunohistochemistry, we evaluated K17 and p27 expression and assessed their biological behavior and prognostic significance in 326 colorectal cancers. High K17 expression was associated with poorly differentiated tumors, high pT classification, and lymph node metastases. Low p27 expression was associated with large tumors, high pT classification, lymphovascular invasion, and lymph node metastases. The overall survival of patients with high K17 expression was significantly worse than that of patients with low K17 expression [hazard ratio (HR) = 1.805, 95% confidence interval (CI) 1.169-2.787; p = 0.007]. Patients with low p27 expression showed significantly worse overall survival than those with high p27 expression (HR = 3.082, 95% CI 1.722-5.517; p < 0.001). When combining the results of K17 and p27 expression, the K17 high p27 low expression group showed the worst overall survival. On the contrary, the K17 high/low p27 high group showed the best overall survival (p < 0.001). Therefore, K17 high p27 low expression is an independent poor prognostic factor in colorectal cancer. Thus, high K17 and low p27 expression correlate with aggressive clinicopathologic behavior and can be used as poor prognostic markers in colorectal cancer., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background: COVID-19 is known to cause psychological problems. Psychological rehabilitation can be performed to reduce anxiety, depression, and insomnia. Facing patients with infectious diseases can be difficult for medical staff. Therefore, this study compared the effects of psychiatric tele-rehabilitation (TR) and conventional psychiatric rehabilitation (CR) in isolated patients with COVID-19., Methods: This randomized controlled study, conducted at a single community-based hospital, included 40 patients (24 in the psychiatric tele-rehabilitation group [TRG] and 16 in the conventional psychiatric rehabilitation group [CRG]) with COVID-19 were recruited from November 18, 2021, to April 7, 2022. Psychiatric rehabilitation is an occupation-based intervention in which patients perform meaningful activities and tasks. Patients in the TRG selected activities, received counseling, and underwent monitoring over the phone, while those in the CRG participated in face-to-face sessions. The interventions were conducted for 50 min each day during an isolation period of 7 days in both groups, and all participants received the interventions individually. The primary outcome was anxiety assessed using the Visual Analog Scale (VAS) and the Zung Self-Rating Anxiety Scale (SAS). Secondary outcomes include the Visual Analog Scale (VAS) and the Patient Health Questionnaire-9 (PHQ-9) to evaluate depression, the Multidimensional State Boredom Scale-8 (MSBS-8) to assess boredom. The Korean version of the Insomnia Severity Index (ISI-K) was used to assess the quality of sleep, and the World Health Organization Quality of Life Assessment Instrument-BRIEF (WHOQOL-BREF) was used to evaluate quality of life. Questionnaires were administered at admission, discharge, and at the 6-month follow-up., Results: In the time × group analysis, the SAS total score (p = .033) and the VAS score for depression (p = .012) in the CRG were significantly lower than those in the TRG at the time of discharge. The VAS score for anxiety (p = .007), total SAS score (p = .050), and VAS score for depression (p = .003) in the CRG were also significantly lower than those in the TRG at the 6-month follow-up. The PHQ-9, MSBS-8, ISI-K, and WHOQOL-BREF scores showed no significant interactions in the time × group analysis., Conclusions: TR was effective in reducing anxiety and improving quality of life during hospitalization, but had no remained effects after discharge. Otherwise, CR was more effective than TR for anxiety and depression during hospitalization and had remained effects at 6-month follow-up. However, considering the characteristics of infectious conditions that involve risk in contact, TR will still play an important role, and efforts will be needed to improve the effect that remained., Trial Registration: The trial was registered with the Korea Clinical Trials Registry (KCT0006714, Date of registration 08/11/2021)., Competing Interests: Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Seoul National University Bundang Hospital (B-2111-719-302). The requirement for obtaining written informed consent was waived by the Institutional Review Board of Seoul National University Bundang Hospital (B-2111-719-302). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study proposes a synthetic data generation model to create a classification framework for cerebellar ataxia patients using trajectory data from the visuomotor adaptation task. The classification objectives include patients with cerebellar ataxia, age-matched normal individuals, and young healthy subjects. Synthetic data for the three classes is generated based on class conditions and random noise by leveraging a combination of conditional adversarial generative neural networks and reconstruction networks. This synthetic data, alongside real data, is utilized as training data for the patient classification model to enhance classification accuracy. The fidelity of the synthetic data is assessed visually to measure the validity and diversity of the generated data qualitatively while quantitatively evaluating distribution similarity to real data. Furthermore, the clinical efficacy of the patient classification model employing synthetic data is demonstrated by showcasing improved classification accuracy through a comparative analysis between results obtained using solely real data and those obtained when both real and synthetic data are utilized. This methodological approach holds promise in addressing data insufficiency in the digital healthcare domain, employing deep learning methodologies, and developing early disease diagnosis tools., Competing Interests: Declarations Ethics approval and consent to participate All experimental procedures, including recruitment, were conducted in accordance with ethical guidelines and procedures approved by the Institutional Review Board of Seoul Metropolitan Government Seoul National University Boramae Medical Center (IRB no. 30-2019-88). All participants gave their written informed consent prior to participation. Consent for publication N/a. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Choice involves engaging in a selection response when multiple options are concurrently available. Choices can be incorporated into many components of behavior-analytic treatment such as providing clients with a choice between multiple items, activities, or tasks. We reviewed the main characteristics of 38 behavior-analytic articles that compared choice and no-choice conditions. We coded the experimental arrangements of choice and no-choice conditions and analyzed potential factors affecting preferences for choice and no choice. The findings suggest that the sizing of alternatives from which to choose, the timing of choice opportunities, and the timing of the delivery of the chosen option varied across the studies. Furthermore, preferences for choice shifted with differential reinforcement history and response effort manipulations of choice or no choice. The findings suggest that individual variables should be considered when providing choices, but more research is needed., (© 2024 The Author(s). Journal of Applied Behavior Analysis published by Wiley Periodicals LLC on behalf of Society for the Experimental Analysis of Behavior (SEAB).)

Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker., (© The Author(s) 2024. Published by Oxford University Press.)

Biotin is an essential coenzyme involved in various metabolic processes across all known organisms, with biotinylation being crucial for the activity of carboxylases. BirA from Haemophilus influenzae is a bifunctional protein that acts as a biotin protein ligase and a transcriptional repressor. This study reveals the crystal structures of Hin BirA in both its apo- and holo-(biotinyl-5'-AMP bound) forms. As a class II BirA, it consists of three domains: N-terminal DNA binding domain, central catalytic domain, and C-terminal SH3-like domain. The structural analysis shows that the biotin-binding loop forms an ordered structure upon biotinyl-5'-AMP binding. This facilitates its interaction with the ligand and promotes protein dimerization. Comparative studies with other BirA homologs from different organisms indicate that the residues responsible for binding biotinyl-5'-AMP are highly conserved. This study also utilized AlphaFold2 to model the potential heterodimeric interaction between Hin BirA and biotin carboxyl carrier protein, thereby providing insights into the structural basis for biotinylation. These findings enhance our understanding of the structural and functional characteristics of Hin BirA, highlighting its potential as a target for novel antibiotics that disrupt the bacterial biotin synthesis pathways., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's disease is one of at least 26 diseases characterized by tau-positive accumulation in neurons, glia or both. However, it is still unclear what modifications cause soluble tau to transform into insoluble aggregates. We previously performed genetic screens that identified tyrosine kinase 2 (TYK2) as a candidate regulator of tau levels. Here we verified this finding and found that TYK2 phosphorylates tau at tyrosine 29 (Tyr29) leading to its stabilization and promoting its aggregation in human cells. We discovered that TYK2-mediated Tyr29 phosphorylation interferes with autophagic clearance of tau. We also show that TYK2-mediated phosphorylation of Tyr29 facilitates pathological tau accumulation in P301S tau-transgenic mice. Furthermore, knockdown of Tyk2 reduced total tau and pathogenic tau levels and rescued gliosis in a tauopathy mouse model. Collectively, these data suggest that partial inhibition of TYK2 could thus be a strategy to reduce tau levels and toxicity., Competing Interests: Competing interests H.Y.Z. cofounded Cajal Neuroscience, is a director of the Regeneron Pharmaceuticals board and is on the scientific advisory board of Cajal Neuroscience, Lyterian and the Column Group. D.M.H. cofounded and is on the scientific advisory board of C2N Diagnostics. D.M.H. is on the scientific advisory board of Denali, Cajal Neuroscience and Genentech, consults for Asteroid Therapeutics, is an inventor of and has a patent on antitau antibodies that was licensed by Washington University to C2N Diagnostics. B.H. owns stock in Novartis; he serves on the scientific advisory board of Dewpoint and has an option for stock. He serves on a scientific advisory board or is a consultant for AbbVie, Alexion, Ambagon, Aprinoia Therapeutics, Arvinas, Avrobio, AstraZeneca, Biogen, BMS, Cure Alz Fund, Cell Signaling Technology, Dewpoint, Latus, Novartis, Pfizer, Sanofi, Sofinnova, Vigil, Violet, Voyager and WaveBreak. His laboratory is supported by research grants from the NIH, Cure Alzheimer’s Fund, Tau Consortium and the JPB Foundation, as well as a sponsored research agreement from Abbvie. The other authors declare no competing interests., (© 2024. The Author(s).)

Background: Renal replacement therapy (RRT) is an important treatment option for sepsis-associated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies., Methods: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsis-associated AKI, respectively., Results: Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsis-associated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3-25) and vasopressor administration (median, 21; IQR, 5-26) than the late CKRT group did (median, 10.5; IQR, 0-23; P = 0.037 and median, 13.5; IQR, 0-25; P = 0.028, respectively). The Kaplan-Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040). In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237)., Conclusion: Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Objectives: This study investigates the association between toothbrushing frequency and self-rated oral health to evaluate the effectiveness of the 3-3-3 toothbrushing campaign., Methods: Employing a cross-sectional study design, we analysed responses from 13,199 adults using structured questionnaires. The dependent variable was self-rated oral health. The independent variables were toothbrushing habits. We compared both groups; control group: twice a day and case group: three times a day. Predisposing, enabling and need factors were adjusted as confounders based on the Anderson behaviour model., Results: Our findings reveal no significant correlation between toothbrushing frequency (twice vs. three times daily) and self-perceived oral health status. These results suggest re-evaluating the 3-3-3 campaign's recommendations. Further research is necessary to identify factors that more directly influence self-rated oral health., Conclusion: Our research found that increasing toothbrushing from twice to three times daily does not significantly enhance oral health, as evidenced by an odds ratio of 0.97 and a negligible Cohen's d value. We recommend public health campaigns emphasise toothbrushing quality over frequency to improve oral health outcomes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Transcriptional regulatory networks (TRNs) in bacteria are crucial for elucidating the mechanisms that regulate gene expression and cellular responses to environmental stimuli. These networks delineate the interactions between transcription factors (TFs) and their target genes, thereby uncovering the regulatory processes that modulate gene expression under varying environmental conditions. Analyzing TRNs offers valuable insights into bacterial adaptation, stress responses, and metabolic optimization from an evolutionary standpoint. Additionally, understanding TRNs can drive the development of novel antimicrobial therapies and the engineering of microbial strains for biofuel and bioproduct production. This protocol integrates advanced data analysis pipelines, including ChEAP, DEOCSU, and DESeq2, to analyze omics datasets that encompass genome-wide TF binding sites and transcriptome profiles derived from ChIP-exo and RNA-seq experiments. This approach minimizes both the time required and the risk of bias, making it accessible to non-expert users. Key steps in the protocol include preprocessing and peak calling from ChIP-exo data, differential expression analysis of RNA-seq data, and motif and regulon analysis. This method offers a comprehensive and efficient framework for TRN reconstruction across various bacterial strains, enhancing both the accuracy and reliability of the analysis while providing valuable insights for basic and applied research., Competing Interests: Declarations Conflict of interest The authors have no conflict of interest to report., (© 2024. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Background: This study aimed to compare the outcomes and complications of active young adults undergoing open reduction and plate fixation (ORPF) and intramedullary nailing (IMN) for displaced midshaft clavicle fractures (MCFs)., Methods: A retrospective review was performed on all patients undergoing ORPF and IMN of complete MCFs at a single center between 2018 and 2022. Patients who were younger than 60 years with radiographic follow-up until union were included in the study. The mean age of the patients was 33.1 years. Outcome measures were achievement of union, time to healing, residual deformity, complications, and need for additional procedures., Results: Of 39 patients, 29 underwent ORPF and 10 underwent IMN. Plate fixation provided faster functional recovery in the first 6 months, but no difference was observed after 1 year. All fractures in the IMN group healed (100%), compared to 90% in the ORPF group (P=0.08). Mean time to union was 21±8.9 weeks and was significantly different between the two groups (P<0.01), with the ORPF group averaging 23.1 weeks and the IMN group 20.8 weeks. Nonunion rates were higher in the ORPF group (10.3%) than in the IMN group (0.0%), but the difference was not significant (P=0.10)., Conclusions: Both methods restored patients to their pre-injury functional levels. However, IMN, with its higher healing rate, fewer required revision surgeries, and lower incisional numbness, appears to be the preferred method for treating MSFs without comminution in young adults. Level of evidence: III.

Background: The quantification of mRNA expression in urinary sediments is a reliable biomarker for various diseases. However, few studies have investigated the clinical relevance of urinary mRNA levels in IgA nephropathy (IgAN). Thus, we investigated the expression of urinary mRNAs and their clinical significance in IgAN., Methods: Overall, 200 patients with biopsy-proven IgAN, 48 disease controls, and 76 healthy controls were enrolled. We identified the differential expression of mRNAs in renal tissue between patients with IgAN and normal subjects using the Gene Expression Omnibus dataset and selected candidate mRNAs. mRNA expression in the urinary sediment was measured using quantitative real-time polymerase chain reaction. Associations between urinary mRNA levels and clinicopathological parameters were analyzed and the predictive value of mRNAs for disease progression was evaluated., Results: The urinary expression of CCL2, CD14, DNMT1, FKBP5, Nephrin, and IL-6 was significantly upregulated in patients with IgAN compared with healthy controls. C3, FLOT1, and Podocin levels were significantly correlated with renal function, where C3, FLOT1, and TfR levels were significantly correlated with urinary protein excretion. During follow-up, 26 (13.0%) patients with IgAN experienced disease progression, defined as a greater than 50% reduction in the estimated glomerular filtration rate or progression to end-stage renal disease. Urinary mRNA levels of FLOT1 (HR 3.706, 95% CI 1.373-10.005, P = 0.010) were independently associated with an increased risk of disease progression., Conclusions: Our results suggest that urinary sediment mRNAs are a useful biomarker in IgAN patients. Further studies with larger sample sizes and longer follow-up durations are required., (© 2024. The Author(s).)

Introduction: Despite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations., Methods: RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co-expression network, gene-set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography., Results: DGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD-associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell-mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data., Discussion: Our results in a Korean population suggest Aβ deposition-associated genes are enriched in NK cell-mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies., Highlights: Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network modules were associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβ deposition. Dysregulated genes were related to a NK cell-mediated immunity., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Confinement of reactants within nanoscale spaces of low-dimensional materials has been shown to provide reorientation of strained reactants or stabilization of unstable reactants for synthesis of molecules and tuning of chemical reactivity. While few studies have reported chemistry within zero-dimensional pores and one-dimensional nanotubes, organic reactions in confined spaces between two-dimensional materials have yet to be explored. Here, we demonstrate that reactants confined between atomically thin sheets of graphene or hexagonal boron nitride experience pressures as high as 7 gigapascal, which allows the propagation of solvent-free organic reactions that ordinarily do not occur under standard conditions. Specifically, we show that cyclodehydrogenation of hexaphenylbenzene without catalysts as a proof of concept and oxidative polymerization of dopamine into sheet-like crystalline structure are enabled by the effective high pressure experienced by the reactants between the graphene layers. Our results demonstrate a facile, general approach for performing high-pressure chemistry based on confinement of reactants within two-dimensional materials.

The growth of Caenorhabditis elegans involves multiple molting processes, during which old cuticles are shed, and new cuticles are rapidly formed. This process requires the regulated bulk secretion of cuticle components. The transmembrane protein-39 (TMEM-39) mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles. TMEM-39 primarily co-localizes with the coat protein II complex (COPII) in large vesicles rather than small COPII vesicles. These TMEM-39-associated large vesicles (TMEM-39-LVs) form robustly during the molting period and co-localize with various extracellular matrix (ECM) components, including BLI-1 collagen, BLI-3 dual oxidase, and carboxypeptidases. Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells, we identify TMEM39A-associated proteins, including TMEM131. Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C. elegans and human sarcoma cells, indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles. Given the conservation of TMEM39A and its associated proteins between C. elegans and humans, TMEM39A-LV may represent a fundamental machinery for rapid and extensive secretion across metazoans., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Idiopathic pulmonary fibrosis (IPF) can occur at any age; however, studies on younger IPF patients are scarce because it primarily affects the elderly. This study aimed to investigate the clinical features and outcomes of younger IPF patients., Methods: We analyzed the National Korean Health Insurance Review and Assessment Service (HIRA) database from 2015 to 2021. Patients with IPF were identified using the International Classification of Diseases 10th Revision (ICD-10) codes and the Rare Intractable Diseases codes and were categorized into three age groups: <50, ≥50 and <65, and ≥65 years. The risk of acute exacerbation (AE) and mortality was analyzed., Results: Among 4,243 patients with IPF, 91 were under 50. These younger patients, who were predominantly female, exhibited less comorbidities and received more systemic steroids, whereas older group received more pirfenidone. Although AE risk increased with age, it was not statistically significant. Mortality and lung transplantation risks increased notably with age from the <50 group to the ≥50 and <65 group (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 0.93-2.49) and the ≥65 group (HR: 2.44, 95% CI: 1.51-3.93). These risks were influenced by factors such as age, comorbidities, previous AEs, and steroid use. Conversely, pirfenidone treatment reduced the risk., Conclusion: While younger IPF patients had a lower risk of mortality and lung transplantation, with no significant differences in the risk of AEs, they were less likely to receive antifibrotic therapy and more often treated with steroids, which may affect outcomes. Early, targeted treatment strategies, including antifibrotic use, are crucial for improving their prognosis., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians., Methods: Vascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid positivity were assessed at baseline and longitudinally., Results: Baseline analyses revealed that amyloid-negative (Aβ-) cognitively normal (CN) individuals with high FRS had lower cognition compared to Aβ- CN individuals with low FRS (p < 0.0001). Longitudinally, amyloid pathology predominantly drove cognitive decline, while FRS alone had negligible effects on cognition in CN and mild cognitive impairment (MCI) groups., Conclusion: Our findings indicate that managing vascular risk may be crucial in preserving cognition in Aβ- individuals early on and before the clinical manifestation of dementia. Within the CN and MCI groups, irrespective of FRS status, amyloid-positive individuals had worse cognitive performance than Aβ- individuals., Highlights: Vascular risk significantly affects cognition in amyloid-negative older Koreans. Amyloid-negative CN older adults with high vascular risk had lower baseline cognition. Amyloid pathology drives cognitive decline in CN and MCI, regardless of vascular risk. The study underscores the impact of vascular health on the AD disease spectrum., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Delay discounting refers to the devaluation of an outcome as temporal delay increases. Steep discounting is characterized by preferring a smaller, immediate outcome over a larger, delayed outcome and is associated with maladaptive behaviors such as tobacco use. Previous studies have compared delay discounting outcomes between combustible cigarette (CC) smokers and nonusers using various discounting tasks. With the growing use of electronic cigarettes (e-cigarettes [EC]) and various delay discounting tasks available to researchers, we extended previous work in delay discounting and EC use in two ways. The present study assessed delay discounting in a web-based sample of 259 participants to (a) establish convergent validity across four different delay discounting tasks and (b) compare the outcomes between four subgroups: dual users, exclusive EC users, exclusive CC users, and nonusers. The four delay discounting tasks (Monetary Choice Questionnaire, 5-Trial Adjusting Delay Discounting Task [ADT-5], Temporal Discounting Questionnaire, and Brief Intertemporal Choice Task [BRIC Task]) showed moderate to strong convergent validity ( p < .001). Further, findings indicated significant differences between all four subgroups across the four different delay discounting tasks ( p < .048) with small effect sizes. Pairwise comparisons showed that exclusive EC users exhibited significantly steeper discounting than nonusers in ADT-5 ( p = .043) and BRIC Task ( p = .029) and dual users exhibited significantly steeper discounting than nonusers on ADT-5 ( p = .043) and BRIC Task ( p = .030). Our findings replicate previous findings and suggest the potential role of delay discounting in explaining the behavioral mechanism underlying e-cigarette use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models., Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis., Conclusions: NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation., (© 2024. The Author(s).)

We studied the hydroboration of the C 70 fullerene using both B3LYP-D3(BJ)/6-311G(d,p) and M06-2X-D3/6-311G(d,p) levels of theory, incorporating the empirical dispersion interaction, and Fukui index calculations. Potential energy surfaces (PESs) and Gibbs free energy surfaces (GFESs) were calculated for the pathways from four BH 3 adducts (located at the AB , CC , D , and E sites) on the C 70 to eight products formed by the 1,2-addition of BH 3 across the four [6,6]-ring fused bonds ( AB , CC , DE , and EE ) and across the two [5,6]-ring fused bonds ( AA and DD ). These pathways are two-step consecutive reactions. We denoted the positions on the fullerene cage as A through E , from the pole to the equator, based on the D 5h symmetry of the C 70 fullerene. In the first step reaction, the product ratios for the four adduct intermediates should be as the primary intermediate BH 3 ( D ), the secondary intermediate BH 3 ( AB ), the tertiary intermediate BH 3 ( CC ), and the minor intermediate BH 3 ( E ), based on the Fukui indices. In addition, in the second step reaction, transition states (TSs) from four adduct intermediates to eight product isomers, namely, BH 2 ( A )H ( B ) to BH 2 ( E )H ( E ), were obtained using the QST2 method. The calculated reaction coordinates showed exothermic reactions for all bonds except the EE bond. We also confirmed the transition states by frequency calculations and intrinsic reaction coordinate (IRC) analyses. The PESs and GFESs suggest spontaneous processes for the four isomers, of which the primary products are BH 2 ( A )H ( B ) and its isomer BH 2 ( B )H ( A ), the secondary product is BH 2 ( C )H ( C ), and the tertiary product is BH 2 ( D )H ( D ), all formed through adduct intermediates. Therefore, through the hydroboration reaction of C 70 , we could predict and design the site selectivity of C 70 by controlling the energy barrier of the transition state in the second step of the reaction. This implies that we could selectively synthesize mainly BH 2 ( B )H ( A ) isomers across the AB-[6,6]-ring fused bond and also design BH 2 ( D )H( D ) isomers across the DD-[5,6]-ring fused bond. Also, the calculations of formation rate constants can well simulate the experimental ratio of two C 70 H 2 isomers by the hydrolysis of BH 2 ( A )H( B ), BH 2 ( B )H( A ), and BH 2 ( C )H( C ) products at room temperature.

Negative photoconductivity (NPC)-based photodetectors offer a new direction for energy-efficient photodetection technologies, featuring low energy consumption and high responsivity. Two-dimensional (2D) materials are particularly promising for implementing NPC due to their large surface area, abundant surface states, and tunable bandgap properties. In this context, 2D Nb 3 Cl 8 , with its unique kagome lattice structure and broad absorption spectrum, has attracted considerable interest. Notably, metal halides such as Nb 3 Cl 8 demonstrate significant potential as NPC materials due to their low anionic and cationic bonding strength, which allows for the formation of vacancy defects with high probability. However, the NPC characteristics of Nb 3 Cl 8 have not been thoroughly investigated. In this study, we fabricated field-effect transistors (FETs) using Nb 3 Cl 8 single crystals synthesized via chemical vapor transport (CVT). These devices exhibited an electron mobility of 4.24 × 10 -3 cm 2 V -1 s -1 and a high I on / I off ratio of 1.42 × 10 4 . Notably, Nb 3 Cl 8 -based photodetectors demonstrated consistent NPC behavior across a wide wavelength range of 400-1050 nm, with a high responsivity of 156.82 mA W -1 at 400 nm. We propose that the trapping effect due to defect levels within the bandgap is the primary cause of this NPC phenomenon. The present findings reveal the unique photodetector properties of Nb 3 Cl 8 and highlight its promise in energy-efficient photodetectors and various optoelectronic applications.

Background and Purpose: Vertebrobasilar artery stent placement (VBS) is potentially effective in preventing recurrent posterior circulation strokes; however, the incidences of in-stent restenosis and stented-territory ischemic events based on the location of stent placement have rarely been investigated. We aimed to investigate the characteristics and prognosis of VBS between intracranial and extracranial., Materials and Methods: This study was single-center retrospective cohort study, and we obtained medical records of patients who underwent VBS. We compared clinical and periprocedural factors between extracranial and intracranial VBS. The primary outcomes included the incidence of in-stent restenosis (>50% reduction in lumen diameter) and stented-territory ischemic events. We compared the incidence of in-stent restenosis and stented-territory ischemic events by using Kaplan-Meier curves., Results: Of the 105 patients, 41 (39.0%) underwent extracranial VBS, and 64 (61.0%) underwent intracranial VBS. During the follow-up, the incidences of in-stent restenosis and stented-territory ischemic events were 15.2% and 22.9%, respectively. The procedure time was longer (47.7 ± 19.5 minutes versus 74.5 ± 35.2 minutes, P < .001), and the rate of residual stenosis (≥30%) just after VBS was higher (2 [4.9%] versus 24 [37.5%], P < .001) in intracranial VBS than in extracranial VBS. Also, the incidences of in-stent restenosis were significantly higher in intracranial VBS than in extracranial VBS (4.9% versus 21.9%, P = .037). On the other hand, the incidences of stented-territory ischemic events (7.3% versus 32.8%, P < .001) were significantly higher in intracranial VBS than in extracranial VBS. The main mechanisms of stroke were artery-to-artery embolism (2 [66.7%]) in extracranial VBS, and artery-to-artery embolism (9 [42.9%]) and branch atheromatous disease (8 [38.1%]) in intracranial VBS. The Kaplan-Meier curve demonstrated a higher incidence of in-stent restenosis and stented-territory ischemic events in intracranial VBS than in extracranial VBS ( P = .008 and P = .002, respectively)., Conclusions: During the follow-up, the incidence of in-stent restenosis and stented-territory ischemic events was higher in patients with intracranial VBS than in those with extracranial VBS. The higher rates of postprocedural residual stenosis might have contributed to the increased risk of in-stent restenosis. Furthermore, prolonged procedure time and additional stroke mechanism, including branch atheromatous disease, might be associated with a higher risk of stented-territory ischemic events in intracranial VBS., (© 2024 by American Journal of Neuroradiology.)

Objective: To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Design: This population-based cohort study was conducted using a nationwide healthcare claims database (2014-2022) of Korea. We included individuals with MASLD (aged ≥40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimated HRs with 95% CIs., Results: After 1:1 propensity score matching, we included 22 550 patients who initiated SGLT-2i and GLP-1RA (median age=57 years, 60% male), and 191 628 patients who initiated SGLT-2i and TZD (median age=57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.93, 95% CI 0.76 to 1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR 0.77, 95% CI 0.72 to 0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR 0.87 (95% CI 0.80-0.94); female: HR 0.62 (95% CI 0.55-0.69))., Conclusions: In this nationwide cohort study, SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, while demonstrating similar effectiveness to GLP-1RA., Competing Interests: Competing interests: J-YS received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, and pharmaceutical companies, including LG Chem, UCB, SK bioscience and Pfizer, outside the submitted work., (© 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.)

Calcific aortic valve disease (CAVD) is a considerable health burden with a lack of effective therapeutic options. There is an urgent need to develop interventions that inhibit the osteogenic transformation of valvular interstitial cells (VICs) and delay the calcification process. Niclosamide, an FDA-approved anti-helminthic drug, has emerged as a promising candidate that demonstrates a negative regulatory effect on porcine VICs calcification. However, its molecular mechanism in human VICs (hVICs) remains to be investigated. In this study, high-resolution mass spectrometry-based proteomics and phosphoproteomics were employed, and 8373 proteins and 3697 phosphosites were identified in hVICs treated with a pro-calcifying medium and niclosamide. The quantitative proteomic and phosphoproteomic analysis resulted in the identification of calcification markers and osteogenesis-associated proteins. Bioinformatic analysis of the protein-protein interaction network and affected kinase prediction revealed that the AMPK/mTOR/p70S6K signaling cascade was altered upon calcific induction and niclosamide treatment. Further validation indicated that niclosamide inhibited the calcification of hVICs by targeting the mammalian target of the rapamycin (mTOR) signaling pathway. This study provides the first evidence that niclosamide could prevent osteoblastic differentiation in hVICs partially through the inhibition of the AMPK/mTOR/p70S6k signaling pathway, thereby mitigating hVICs calcification. These findings present a foundation for potential therapeutic strategies to impede the progression of CAVD and provide valuable insights into the pharmacological effects of niclosamide on human VICs., 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.)

The ability to learn novel motor skills is essential for patients with Parkinson's disease (PD) to regain activities of daily living. However, the underlying mechanisms of motor learning in PD remain unclear. To identify motor features that are distinctively manifested in PD during motor learning, we quantified a rich set of variables reflecting various aspects of the learning process in a virtual throwing task. While the performance outcome improved similarly over 3 days of practice for both PD patients and age-matched controls, further analysis revealed distinct learning processes between the two groups. PD patients initially performed with a slow release velocity and gradually increased it as practice progressed, whereas the control group began with an unnecessarily rapid release velocity, which they later stabilized at a lower value. Performance characteristics related to the timing of ball release and the inter-release interval did not show significant group differences, although they were modulated across practice in both groups. After one week, both groups retained the performance outcomes and underlying kinematics developed over practice. This study underscores the importance of analyzing the multi-faceted learning process to characterize motor skill learning in PD. The findings may provide insights into PD pathophysiology and inform rehabilitation strategies., (© 2024. The Author(s).)

Introduction: This study aimed to analyze the factors affecting the occurrence of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) in patients using anti-resorptive drugs (ARDs) on different implant position, inclinations, and types of prosthesis., Methods: The data of 75 patients with bone necrosis that progressed around the implant between 2018 and 2022 were retrospectively examined to identify the factors influencing PI-MRONJ. Data, including patient demographics (age, sex, smoking status, concomitant disease, time of ARD therapy, dose of ARDs, and parafunctional habits) and implant-specific information (type of prosthesis, angle of insertion), were extracted from medical and dental records., Results: Tilted implants with an angle ≥ 5.1° relative to the occlusal plane of the prosthesis had a stronger association with PI-MRONJ in comparison to non-tilted implants (inclination was < 5°). Additionally, the boundary of the area of osteonecrosis around the fixture was larger for the splinted implant-supported crowns than for the single implant supported crowns)., Conclusion: In patients taking anti-resorptive medications the inclination of the implant was associated with the occurrence of PI-MRONJ. Further studies are required to confirm the clinical findings., (© 2024 The Author(s). Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)