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Endogenous retroviruses (ERVs) are remnants of ancient parasitic infections and comprise sizable portions of most genomes. Although epigenetic mechanisms silence most ERVs by generating a repressive environment that prevents their expression (heterochromatin), little is known about mechanisms silencing ERVs residing in open regions of the genome (euchromatin). This is particularly important during embryonic development, where induction and repression of distinct classes of ERVs occur in short temporal windows. Here, we demonstrate that transcription-associated RNA degradation by the nuclear RNA exosome and Integrator is a regulatory mechanism that controls the productive transcription of most genes and many ERVs involved in preimplantation development. Disrupting nuclear RNA catabolism promotes dedifferentiation to a totipotent-like state characterized by defects in RNAPII elongation and decreased expression of long genes (gene-length asymmetry). Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards RNAPII activity, ERV expression, cell identity, and developmental potency.

Background Anemia is a common complication of chronic kidney disease (CKD). In patients with CKD-related anemia, an inverse relationship between vitamin D and hepcidin levels has been observed. Hepcidin is a key regulator of iron homeostasis, mediated via binding to ferroportin. The aim of this study was to investigate the effects of cholecalciferol and omega-3 fatty acids (FA) on hepcidin levels using 5/6 nephrectomized (Nx) rats. Methods Male Sprague-Dawley rats were divided into five groups: sham control, 5/6 Nx, 5/6 Nx treated with cholecalciferol, 5/6 Nx treated with omega-3 FA, and 5/6 Nx treated with both cholecalciferol and omega-3 FA. We measured the hepcidin and ferroportin levels in the kidney and liver by enzyme-linked immunosorbent assays and Western blots. We evaluated hepcidin expression in the kidney by immunohistochemical staining. Results Among the five groups, 5/6 Nx rats exhibited the worst kidney function. Compared with the sham controls, 5/6 Nx rats showed significantly increased serum hepcidin levels and decreased vitamin D levels. Supplementation with either omega-3 FA or cholecalciferol decreased hepcidin and increased vitamin D levels, with a concurrent improvement of anemia. Furthermore, 5/6 Nx rats treated with omega-3 FA/cholecalciferol showed decreased ferroportin and ferritin levels, while iron and total iron-binding capacity levels increased. Conclusions Treatment with a combination of cholecalciferol and omega-3 FA may improve anemia in a CKD rat model by decreasing hepcidin levels.

Abstract Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer’s disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer’s disease.

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination.

Abstract An unprecedented silver‐mediated intramolecular oxy‐argentation of 3‐amidoaryne precursors that quickly generates a heteroarylsilver species is developed. AgF acts as both a stoichiometric fluoride source and a reagent for the formation of a benzoxazolylsilver intermediate via aryne generation. Pd‐catalyzed coupling reactions of (hetero)aryl iodides with a silver species, generated in situ, allow for the synthesis of various C7‐arylated benzoxazoles. As a result, an aryl group is selectively introduced into the meta‐position of 3‐amidobenzyne precursors. Mechanistic studies have indicated the presence of a benzoxazolylsilver intermediate and revealed that the reaction proceeds via an intramolecular oxy‐argentation process, which is initiated by a direct fluoride attack on the silyl group.

Canopy coverage-based crop growth monitoring is highly dependent on the performance of crop segmentation algorithms. Under field conditions, crop segmentation for unmanned aerial vehicle (UAV) imagery should be sophisticated considering geometric distortion of images by wind and illumination variations. Under Korean cultivation conditions, a plastic mulch used to restrict weeds and prevent cold weather damage increases the complexity of the image background. In particular, on-site monitoring of onion and garlic growth has been limited by their morphology because they have long narrow leaves. The ultimate goal of this study was to quantify the growth parameters of onion and garlic at multiple growth stages using red, green, and blue (RGB) imagery obtained with UAVs. Canopy coverage and plant height were used as predictor variables to develop mathematical models to estimate the fresh weights of onion and garlic. The use of a CIE L*a*b* color space and mean shift (MS) algorithm enhanced the extraction of the canopy coverage of onion and garlic from complex backgrounds, including plastic mulch, soil, and shadows under varying illumination conditions. Multiple linear regression models consisting of the a* band-based vegetation fraction (VF) and structure from motion (SfM)-based plant height (PH) fitted the fresh weight data of onion and garlic well with high coefficients of determination (R2) ranging from 0.82 to 0.92. The validation results showed an almost 1:1 slope with highly linear relationships (R2 > 0.82) between the onion and garlic fresh weights obtained with the UAV RGB imagery and actual fresh weights, confirming that the UAV-RGB imagery based on the use of the a*band and PH can be used to quantify the spatial and temporal variability of onion and garlic growth parameters during the growing season.

Background/Aims: Based on their anatomy, cholangiocarcinomas (CCAs) are classified into intrahepatic, hilar, and distal CCAs. Although the diagnosis and treatment of each type of CCA are thought to be different, real-world data studies on the current practice are limited. Therefore, this study was designed to capture the current practice of diagnosing and treating perihilar CCA in Korea. Methods: We conducted a survey using an online platform. The questionnaire consisted of 18 questions designed to evaluate the current practice of diagnosing and treating perihilar CCA in Korea. The targets of this survey were biliary endoscopists who are members of the Korean Pancreatobiliary Association. Results: In total, 119 biliary endoscopists completed the survey. Of the respondents, 89.9% thought that the use of the International Classification of Diseases, 11th Revision (ICD-11) system is necessary to classify CCA. Approximately half of the respondents would recommend surgery or chemotherapy until patients were 80 years of age. For the pathological diagnosis of CCA, endoscopic retrograde cholangiopancreatography with biopsy was the most preferred modality. Routine preoperative biliary drainage was performed by 44.5% of the respondents. For operable CCAs, 64.7% of the respondents preferred endoscopic biliary drainage using plastic stents. For palliative biliary drainage, 69.7% of the respondents used plastic stents. For palliative endoscopic biliary drainage using metal stents, 63% of the respondents preferred the stent-in-stent method. Conclusions: A new coding system using the ICD-11 is needed for classifying CCAs. Guidelines for diagnosing and treating CCA based on the clinical situation in Korea are needed.

Abstract Introduction To estimate herpes zoster (HZ) incidence rate (IR) and economic burden in individuals with immunocompromised conditions and autoimmune diseases (IC/AID) in the Republic of Korea (ROK). Methods The nationwide Health Insurance Review and Assessment Service database was used to identify HZ cases from 2016 to 2020 in ROK. HZ and non-HZ IC/AID cases were matched 1:3 using age, sex, institution, Charlson comorbidity index, IC/AID, and index date. Annual HZ IRs/1000 persons and 1-year HZ-associated all-cause direct medical costs for IC/AID cases were calculated. Results Among 65,976 individuals with IC/AID (mean age 57.14 years [standard deviation 14.1]; 64.94% female), annual HZ IR (95% confidence interval) fluctuated from 2016 to 2020, averaging 23.41/1000 persons (22.21–24.62) and was higher in women (26.85 [25.40–28.31]) than men (18.96 [18.03–19.89]). IRs were highest in individuals aged ≥ 50 years, and in those with transplants (including solid organ and hematopoietic stem cell transplants; 37.12 [35.45–38.79]) and hemato-oncology conditions (35.5 [31.6–39.3]). Mean 12-month all-cause direct medical costs were higher in individuals with IC/AID and HZ (4,759,671 Korean Republic won [KRW]; approximately 4046 United States dollar [USD; according to the 2020 conversion rate from UNCTAD; 1 KRW = 0.00085 USD]) than those without HZ (3,786,658 KRW; 3219 USD). Conclusion Individuals with IC/AID have a substantial disease and economic burden from HZ in ROK, highlighting the need for appropriate HZ prevention measures in the IC/AID population. Plain Language Summary

The consumption of fructose as sugar and high-fructose corn syrup has markedly increased during the past several decades. This trend coincides with the exponential rise of metabolic diseases, including obesity, nonalcoholic fatty liver disease, cardiovascular disease, and diabetes. While the biochemical pathways of fructose metabolism were elucidated in the early 1990s, organismal-level fructose metabolism and its whole-body pathophysiological impacts have been only recently investigated. In this review, we discuss the history of fructose consumption, biochemical and molecular pathways involved in fructose metabolism in different organs and gut microbiota, the role of fructose in the pathogenesis of metabolic diseases, and the remaining questions to treat such diseases.

The most widely used material in electron transport layers (ETL) of inverted organic solar cells (iOSCs) is zinc oxide (ZnO). However, the brittleness, inorganic nature, surface defects, and photocatalytic activity of ZnO lead to poor stability in iOSCs. Herein, the light‐soaking and thermal stability of iOSCs are substantially improved by modifying ZnO surface with polyurethane diacrylate (SAR) or urethane acrylate (OCS)‐based ultraviolet (UV) resins. The UV resins significantly reduce the energy barrier, suppress surface defects, and improve interfacial contact between ZnO ETL and the organic photoactive layer. Notably, the SAR and OCS resins mitigate the photocatalytic activity of ZnO, electrical leakage, and interfacial resistance during photoaging of OSCs. As a result, iOSCs based on modified ZnOs retain over 80% of initial efficiency under 1 sun illumination for light soaking 1000 h. Furthermore, SAR and OCS resins on ZnO surfaces form a robust crosslinked network with excellent solvent resistant properties, which result in enhanced thermal stability. These results reveal that this simple and effective approach is a promising procedure to fabricate high‐performance iOSCs.

Abstract Strategies to enhance autophagy flux have been suggested to improve outcomes in cardiac ischemic models. We explored the role of adiponectin in mediating cardiac autophagy under ischemic conditions induced by permanent coronary artery ligation. We studied the molecular mechanisms underlying adiponectin's cardio‐protective effects in adiponectin knockout (Ad‐KO) compared with wild‐type (WT) mice subjected to ischemia by coronary artery ligation and H9c2 cardiomyocyte cell line exposed to hypoxia. Systemic infusion of a cathepsin‐B activatable near‐infrared probe as a biomarker for autophagy and detection via noninvasive three‐dimensional fluorescence molecular tomography combined with computerized tomography to quantitate temporal changes, indicated increased activity in the myocardium of WT mice after myocardial infarction which was attenuated in Ad‐KO. Seven days of ischemia increased myocardial adiponectin accumulation and elevated ULK1/AMPK phosphorylation and autophagy assessed by Western blotting for LC3 and p62, an outcome not observed in Ad‐KO mice. Cell death, assessed by TUNEL analysis and the ratio of Bcl‐2:Bax, plus cardiac dysfunction, measured using echocardiography with strain analysis, were exacerbated in Ad‐KO mice. Using cellular models, we observed that adiponectin stimulated autophagy flux in isolated primary adult cardiomyocytes and increased basal and hypoxia‐induced autophagy in H9c2 cells. Real‐time temporal analysis of caspase‐3/7 activation and caspase‐3 Western blot indicated that adiponectin suppressed activation by hypoxia. Hypoxia‐induced mitochondrial reactive oxygen species production and cell death were also attenuated by adiponectin. Importantly, the ability of adiponectin to reduce caspase‐3/7 activation and cell death was not observed in autophagy‐deficient cells generated by CRISPR‐mediated deletion of Atg7. Collectively, our data indicate that adiponectin acts in an autophagy‐dependent manner to attenuate cardiomyocyte caspase‐3/7 activation and cell death in response to hypoxia in vitro and ischemia in mice.

Abstract The simple‐structural and volatile solid additive 1,4‐dibromobenzene (DBrB) can outperform organic solar cells (OSCs) fabricated with 1,4‐diiodobenzene and 1,4‐dichlorobenzene in terms of power conversion efficiency (PCE). A remarkable PCE of 17.0% has been achieved in a binary OSC based on DBrB‐optimized photoactive materials processed from non‐halogenated solvents, which is mainly attributed to the formation of a three‐dimensional interpenetrating network and the orderly arrangement of the photoactive materials by improving the intermolecular interaction. This optimized morphology enables efficient charge transfer/transport as well as suppressed charge recombination, resulting in the simultaneous increase in all photovoltaic parameters. More importantly, we demonstrate that non‐halogenated solvent‐processed DBrB enabled PM6:Y6‐HU OSCs with an impressive PCE of 18.6%, which is the highest efficiency yet reported for binary OSCs. This study suggests that the novel DBrB volatile solid additive is an effective approach to optimizing the morphology and thereby improves the photovoltaic performance of OSCs.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Background Cyclosporine A (CsA)-induced kidney injury is characterized by renal impairment with inflammatory cell infiltrations, apoptosis, fibrosis, and hypoxic injury. It is not clear whether omega-3 fatty acids (O-3 FAs), which have anti-inflammatory and antioxidant roles, affect nuclear factor erythroid 2-related factor 2 (Nrf2) expression. The aim of this study was to investigate whether O-3 FAs affect Nrf2 expression and exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in CsA-induced nephropathy. Methods Male Sprague-Dawley rats were divided into control, CsA-treated, and CsA-treated with O-3 FA groups. Nrf2 expression was measured by Western blots and immunohistochemical staining. Results Kidney function was impaired in the CsA-treated rats compared to the controls. Caspase-3 and caspase-7 were activated in the CsA-treated group, and the Bax/Bcl2 ratio was higher. O-3 FAs attenuated these apoptosis-related changes. ED-1 and inhibition of kappa B (IĸB) protein expression were significantly upregulated in the CsA-treated group. Compared to the control group, O-3 FA supplementation attenuated the increased expression of ED-1 and IĸB related to inflammation. Smad2/3, Smad4, and transforming growth factor-β1 were activated in the CsA group, and O-3 FA treatment prevented these changes related to renal fibrosis. The expression of Nrf2 was reduced in CsA-treated rats, but Nrf-2 was increased by O-3 FA treatment. Conclusions We suggest that Nrf2 is a potential mediator induced by O-3 FA supplementation and that it attenuates pro-inflammatory pathways, fibrotic processes, and apoptosis. Further studies are needed to elucidate the crosstalk between Nrf2 expression and signals related to O-3 FA treatment.

Background: Occipital neuralgia (ON) is an established risk factor for headaches in the posterior cervical region. Several conservative treatments by nerve decompression and pain relief are available for ON, but these treatments have limitations. Acupuncture treatment, which is known to demonstrate analgesic effects, involves various stimulation methods, and several studies have reported their clinical benefit. No recent systematic review (SR) has compared each acupuncture type for ON treatment. Thus, this SR aims to investigate the clinical effectiveness of each acupuncture type for treating ON. Methods: We will identify relevant studies using electronic databases, including EMBASE, MEDLINE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Korean Studies Information Service System (KISS), Korean Medical Database, KoreaMed, and National Digital Science Library (NDSL) from the inception until August 2023. The primary outcome will include the numerical change of pain symptoms (visual analog scale and numerical rating scale) and effective rate. Safety and secondary outcomes will include adverse events and quality of life. We will compare the conservative treatment with the acupuncture treatment using network meta-analysis. The Cochrane Collaboration “risk of bias” tools will be used to assess the quality of included trials. The Grades of Recommendation, Assessment, Development, and Evaluation will be used to examine the evidence level. Conclusion: This study will provide clinical evidence of several acupuncture types for ON and help clinicians decide on the best.

Background: To eliminate tuberculosis (TB), World Health Organization (WHO) initiated “The End TB Strategy” with the goal of a 95% reduction in deaths. While many resources are contributed to eradicating TB, a substantial number of TB patients are still unlikely to receive timely treatment. Thus, we aimed to measure healthcare delay and its association with clinical outcomes from 2013 to 2018. Methods: We conducted a retrospective cohort study using linked data of the National Tuberculosis Surveillance Registry and the health insurance claims data of South Korea. We included incident TB patients, and healthcare delay was defined as the period between the first medical visit with TB-related symptoms and the initiation of an anti-TB regimen. We described the distribution of healthcare delay, and the study population was classified into two groups with mean as a cutoff. The association between healthcare delay and clinical outcomes (all-cause mortality, pneumonia, progression to multi/extensively drug-resistant, intensive care unit admission, and mechanical ventilation use) was evaluated using the Cox proportional hazard model. Several stratified and sensitivity analyses were also conducted. Results: Among 39,747 patients with pulmonary TB, mean healthcare delay was 42.3 days and delayed and non-delayed groups, classified by mean (or average), were 10,680 (26.9%) and 29,067 (73.1%), respectively. Healthcare delay was associated with an increased risk of all-cause mortality (HR 1.10, 95% CI 1.03–1.17), pneumonia (HR 1.13, 95% CI 1.09–1.18), and mechanical ventilation use (HR 1.15, 95% CI 1.01–1.32). We also observed the duration-response of healthcare delay. Stratified analyses showed patients with respiratory diseases were at higher risk, and consistent results were observed in sensitivity analyses. Conclusions: We observed a substantial number of patients experiencing healthcare delays, and it was associated with the deterioration of clinical outcomes. Our findings suggest that attention from authorities and healthcare professionals is needed to attenuate the preventable burden caused by TB through timely treatment.

Indoor position fingerprint-based location estimation methods have been widely used by applications on smartphones. In these localization estimation methods, it is very popular to use the RSSI (Received Signal Strength Indication) of signals to represent the position fingerprint. This paper proposes the design of a particle filter for reducing the estimation error of the machine learning-based indoor BLE location fingerprinting method. Unlike the general particle filter, taking into account the distance, the proposed system designs improved likelihood functions, considering the coordinates based on fingerprint points using mean and variance of RSSI values, combining the particle filter with the k-NN (k-Nearest Neighbor) algorithm to realize the reduction in indoor positioning error. The initial position is estimated by the position fingerprinting method based on the machine learning method. By comparing the fingerprint method based on k-NN with general particle filter processing, and the fingerprint estimation method based on only k-NN or SVM (Support Vector Machine), experiment results showed that the proposed method has a smaller minimum error and a better average error than the conventional method.

Background: Until now, studies on colorectal cancer (CRC) have focused on clinicopathological characteristics based on location without considering sex differences. However, as men and women have fundamentally different physiological characteristics, research results in the clinical field are limited. We aimed to elucidate the differences in the clinicopathological characteristics between right-sided CRC (RCC) and left-sided CRC (LCC) according to sex. Methods: We classified 1492 South Korean patients with no history of colon surgery between July 2005 and June 2015 based on tumor location and sex. For these patients, differences in the clinical characteristics according to sex were compared using univariate and multivariate analyses. Results: Of the 1269 patients, 951 (74.9%) had LCC, and 318 (25.1%) had RCC, making LCC approximately three times more common than RCC. When sex was not taken into account, patients with RCC had significantly higher rates of anemia and undifferentiated cancers than the rates in those with LCC. Even considering sex, anemia and undifferentiated cancer were more prevalent in RCC than in LCC in both men and women. In contrast, age over 65 years and abnormal white blood cell count differed between RCC and LCC only in women. Conclusions: The clinicopathologic characteristics of CRC vary according to the location and sex. Therefore, sex must be considered as a fundamental characteristic of personalized treatment.

Coronavirus disease 2019 (COVID-19) is a highly contagious zoonotic respiratory disease with many similarities to influenza. Effective vaccines are available for both; however, rapid viral evolution and waning immunity make them virtually impossible to eradicate with vaccines. Thus, the practical goal of vaccination is to reduce the incidence of serious illnesses and death. Three years after the introduction of COVID-19 vaccines, the optimal vaccination strategy in the endemic period remains elusive, and health authorities worldwide have begun to adopt various approaches. Herein, we propose a COVID-19 vaccination strategy based on the data available until early 2024 and discuss aspects that require further clarification for better decision making. Drawing from comparisons between COVID-19 and influenza vaccination strategies, our proposed COVID-19 vaccination strategy prioritizes high-risk groups, emphasizes seasonal administration aligned with influenza vaccination campaigns, and advocates the co-administration with influenza vaccines to increase coverage.

Tidal flats provide critical habitat for migratory waterbird species; however, populations of migratory waterbirds have significantly declined due to tidal flat loss and degradation caused by human activities, particularly in Asia. Gochang getbol is one of tidal flats located on the southwest coast of South Korea and a center of clam production. Using bird monitoring data collected at five zones (zone1 to zone5) established across Gochang getbol and near coastal area, we examined distribution patterns of migratory bird diversity and conservation-related species along the coast of Gochang getbol. The intensity of human activity ‒ mudflat culture (mostly bivalve) and aquaculture was relatively high at zone2 and zone3, occupying > 30% of 2km circular area surrounding most sample points of these zones. Zone1 and particularly zone4 contained more natural/semi-natural habitats (less disturbed mudflats and wetlands) and zone5 had smallest mudflat than others. Shannon diversity, species richness, and abundance of migratory birds differed between zones (Anova test, P ≤ 0.02) except Shannon diversity in winter. In fall, all values were higher at zone4 than zone3 and zone5. In winter, zone1 showed greatest species richness and higher abundance than zone2, zone3, and zone5. In spring, while most differences were found between zone4 and zone5, abundance at zone4 was somewhat higher than zone2. The results from the fourth corner analysis indicated that abundance of species foraging at mudflat level was positively associated with zone1 (winter) but negatively with zone3 (fall). Sandpipers were positively associated with zone4. Abundance distribution maps of conservation-related species, created by inverse distance-weighted interpolation modeling, also showed high abundance of most conservation-related species at zone4 and 1. The findings of our study suggest the importance of natural/semi-natural habitat, and the possible link between human activity and distribution patterns of migratory birds in Gochang getbol. While we need further investigation on direct response of migratory birds to human activity, areas with low human activity with more natural/semi-natural habitat, e.g., zone4 and zone1 may be crucial for the conservation of migratory birds.

Abstract The transition of polymer solar cells (PSCs) from laboratory‐scale unit cells to industrial‐scale modules requires the development of new p‐type polymers for high‐performance large‐area PSC modules based on environmentally friendly processes. Herein, a series of 1D/2A terpolymers (PBTPttBD) composed of benzo[1,2‐b:4,5‐b’]dithiophene (BDT‐F), thieno[3,4‐c]pyrrole‐4,6(5H)‐dione (TPD‐TT), and benzo‐[1,2‐c:4,5‐c’]dithiophene‐4,8‐dione (BDD) is synthesized for nonhalogenated solvent processed PSC submodules. The optical, electrochemical, charge‐transport, and nano‐morphological properties of the PBTPttBD terpolymers are modulated by adjusting the molar ratio of the TPD‐TT and BDD components. PBTPttBD‐75:BTP‐eC11‐based PSC submodules, processed with o‐xylene, achieve a notable PCE of 11.57% over a 55 cm2 active area. This PCE value is among the highest reported using a nonhalogenated solvent over a 55 cm2 active area module. The optimized PSC submodule exhibits minimal cell‐to‐module loss, which can be attributed to the optimized crystallinity of the PBTPttBD‐75:BTP‐eC11 photoactive layer system and favorable film formation kinetics.

ABSTRACTAntiangiogenic therapy is a recognized method for countering the immunosuppressive tumor microenvironment (TME) and improving anti-tumor immunity. PB101 is a glycosylated decoy receptor that binds to VEGF-A and PlGF with high affinity, based on the VEGFR1 backbone. Here, we elucidated PB101-induced remodeling of tumor angiogenesis and immunity, which enhances anti-PD-L1 immune checkpoint blockade. PB101 inhibited tumor growth by suppressing angiogenesis and enhancing CD8+ T cell infiltration into the tumors. PB101 induced robust reprogramming of antitumor immunity and activates intratumoral CD8+ T cells. Anti-tumor efficacy of PB101 is mostly dependent on CD8+ T cells and IFN-γ. PB101 reprograms tumor immunity in a manner distinct from that of the conventional VEGF decoy receptor, VEGF-trap. With its potent immune-modulating capability, PB101 synergizes with an anti-PD-L1, triggering strengthened antitumor immunity. Combining PB101 and anti-PD-L1 could establish durable protective immunity against tumor recurrence and metastasis. The findings of this study offer scientific rationales for further clinical development of PB101, particularly when used in combination with immune checkpoint inhibitors, as a potential treatment for advanced cancers.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum–produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum–induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

Background Exposure to cadmium and mercury is associated with renal dysfunction. This study aimed to investigate the possible ability of dietary education to decrease blood cadmium and mercury levels in patients with chronic kidney disease (CKD). Methods Twenty-seven patients with CKD were enrolled in this prospective, single-arm pilot study. Patients with blood cadmium levels ≥1.4 μg/L were instructed to reduce their intake of shellfish, while those with blood mercury levels ≥5.0 μg/L were asked to reduce their intake of externally blue-colored fish. Results Seven dialysis patients and 15 pre-dialysis patients completed the study. Compared with baseline, the blood cadmium (2.0±0.7 μg/L vs. 1.8±0.7 μg/L, p=0.031) and mercury levels (4.4±2.6 μg/L vs. 3.5±1.9 μg/L, p=0.005) after 1 year significantly decreased, although the dietary intake was not significantly different in patients with blood cadmium levels ≥1.4 μg/L and blood mercury levels ≥5.0 μg/L. In pre-dialysis patients, kidney function worsened after 1 year compared with that at baseline despite the reduction in blood cadmium and mercury levels. Conclusions Reduction of food intake containing cadmium and mercury may lower the blood cadmium and mercury levels in CKD patients with higher cadmium and mercury levels. Higher blood cadmium levels may cause renal disease progression in pre-dialysis patients, and further studies are necessary to determine the underlying mechanisms.