Incidence and pattern of second primary cancer in patients diagnosed with primary cancer.

The long survival of patients with primary cancer increases the chance of such patients developing second primary cancer (SPC). The development of SPC in cancer survivors exerts a large psychological, social and economic burden on patients and their families. The aim of the present study was to assess the risk of cancer survivors developing SPC. The study included patients who had been diagnosed with a first primary cancer in five organs (stomach, colorectum, lung, breast and thyroid), which are the five most common sites of cancer in patients from Korea, at the regional cancer center in Jeonbuk National University Hospital between January 2007 and December 2009. The standardized incidence ratio (SIR) of SPC according to sex and site was calculated from 5,209 patients who were followed up to September 2017. General incidence was acquired from the National Cancer Registry of Republic of Korea. SPC occurred in 6.2% (323/5,209) of patients, and the incidence of SPC among the five major types of cancer was in the order of breast (8.8%, 46/524), colorectum (8.6%, 86/1,003), gastric (6.6%, 89/1,358), thyroid (4.7%, 67/1,437) and lung cancer (3.9%, 35/887). When all SPC sites were included, the SIRs of SPC in patients with colorectal cancer and breast cancer were >1.0 (1.21 and 1.66, respectively). Breast cancer and thyroid cancer exhibited a high site relationship (P<0.05), and colorectal cancer had a high site relationship with gastric cancer (P<0.05). The present study analyzed the incidence and pattern of SPC in patients with cancer who were diagnosed with primary carcinoma in five organs. The results of the study may be useful for effective follow-up and early detection of SPC in patients with cancer.

Tilorone mitigates the propagation of α-synucleinopathy in a midbrain-like organoid model.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons and the accumulation of Lewy-body protein aggregates containing misfolded α-synuclein (α-syn) in a phosphorylated form. The lack of effective models for drug screens has hindered drug development studies for PD. However, the recent development of in vitro brain-like organoids provides a new opportunity for evaluating therapeutic agents to slow the progression of this chronic disease. METHODS: In this study, we used a 3D brain-like organoid model to investigate the potential of repurposing Tilorone, an anti-viral drug, for impeding the propagation of α-synucleinopathy. We assessed the effect of Tilorone on the uptake of fluorescently labeled α-syn preformed fibrils (sPFF) and sPFF-induced apoptosis using confocal microscopy. We also examined Tilorone's impact on the phosphorylation of endogenous α-syn induced by pathogenic sPFF by immunoblotting midbrain-like organoid extracts. Additionally, quantitative RT-PCR and proteomic profiling of sPFF-treated organoids were conducted to evaluate the global impact of Tilorone treatment on tissue homeostasis in the 3D organoid model. RESULTS: Tilorone inhibits the uptake of sPFF in both mouse primary neurons and human midbrain-like organoids. Tilorone also reduces the phosphorylation of endogenous α-syn induced by pathogenic α-syn fibrils and mitigates α-syn fibril-induced apoptosis in midbrain-like organoids. Proteomic profiling of fibril-treated organoids reveals substantial alterations in lipid homeostasis by α-syn fibrils, which are reversed by Tilorone treatment. Given its safety profile in clinics, Tilorone may be further developed as a therapeutic intervention to alleviate the propagation of synucleinopathy in PD patients.

Application of ChatGPT for Orthopedic Surgeries and Patient Care.

Artificial intelligence (AI) has rapidly transformed various aspects of life, and the launch of the chatbot "ChatGPT" by OpenAI in November 2022 has garnered significant attention and user appreciation. ChatGPT utilizes natural language processing based on a "generative pre-trained transfer" (GPT) model, specifically the transformer architecture, to generate human-like responses to a wide range of questions and topics. Equipped with approximately 57 billion words and 175 billion parameters from online data, ChatGPT has potential applications in medicine and orthopedics. One of its key strengths is its personalized, easy-to-understand, and adaptive response, which allows it to learn continuously through user interaction. This article discusses how AI, especially ChatGPT, presents numerous opportunities in orthopedics, ranging from preoperative planning and surgical techniques to patient education and medical support. Although ChatGPT's user-friendly responses and adaptive capabilities are laudable, its limitations, including biased responses and ethical concerns, necessitate its cautious and responsible use. Surgeons and healthcare providers should leverage the strengths of the ChatGPT while recognizing its current limitations and verifying critical information through independent research and expert opinions. As AI technology continues to evolve, ChatGPT may become a valuable tool in orthopedic education and patient care, leading to improved outcomes and efficiency in healthcare delivery. The integration of AI into orthopedics offers substantial benefits but requires careful consideration and continuous improvement.

Factors Causing Unintended Sagittal and Axial Alignment Changes in High Tibial Osteotomy: Comparative 3-Dimensional Analysis of Simulation and Actual Surgery.

BACKGROUND: Unintended secondary changes in the posterior tibial slope (PTS) and tibial torsion angle (TTA) may occur after medial open-wedge high tibial osteotomy (MOWHTO). In surgical procedures using patient-specific instruments (PSIs), it is essential to reproduce the PTS and TTA that were planned in simulations. PURPOSE: To analyze the factors causing unintended sagittal and axial alignment changes after MOWHTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Overall, 63 patients (70 knees) who underwent MOWHTO using a PSI between June 2020 and June 2023 were retrospectively reviewed. Preoperative and postoperative computed tomography scans were 3-dimensionally reconstructed. Simulated osteotomy was performed so that the weightbearing line could pass through the target point. A PSI gapper was 3-dimensionally printed to fit the posteromedial corner of the osteotomy gap in the simulated HTO model. After MOWHTO using the PSI gapper, the actual postoperative model was compared with the preoperative or simulation model. This assessment included PTS, TTA, hinge axis, and osteotomy-related parameters. Cortical breakage around the lateral hinge was evaluated to assess stability. RESULTS: The mean PTS and TTA did not change in the simulation. However, significant changes were observed in the actual postoperative PTS and TTA (change, -2.4°± 2.2° and -3.9°± 4.7°, respectively). The PTS was reduced, while the TTA decreased with internal rotation of the distal fragment. The difference in the axial hinge axis angle (AHA) between the simulation and actual surgery was the factor most correlated with the difference in the PTS (r = 0.625; P < .001). In regression analysis, the difference in the AHA was the only factor associated with the difference in the PTS (ß = 0.558; P = .001), and there were no factors that showed any significant associations with the difference in the TTA. In subgroup analyses for the change in the TTA, the correction angle and anterior osteotomy angle were significantly higher in the more internal rotation group (P = .023 and P = .010, respectively). The TTA change was significantly higher in the unstable group with lateral cortical breakage (P = .018). The unstable group was more likely to show an internal rotation of ≥5° (odds ratio, 5.0; P = .007). CONCLUSION: The AHA was associated with a difference in the PTS between the simulation and actual surgery. The change in the TTA was caused by a combination of multiple factors, such as a large correction angle and anterior osteotomy angle, but mainly by instability of the lateral cortical hinge.

Clinical characteristics of the "Gap" between the prevalence and incidence of hearing loss using National Health Insurance Service data.

OBJECTIVES: Hearing loss is the inability to hear speech or sounds well, owing to a number of causes. This study aimed to simultaneously determine the prevalence, incidence, and the Gap between them in hearing loss in South Korean patients at the same point in time as well as to identify patients who have not recovered from hearing loss. METHODS: We examined the prevalence and incidence of patients diagnosed with hearing loss in the National Health Insurance Service database over an 11-year period from 2010 to 2020. The difference between the prevalence and the incidence was defined in this study as the term "Gap". Gap is the number of patients converted into the number of patients per 100,000 people by subtracting the incidence from the prevalence. Clinical characteristics such as sex and age per 100,000 individuals were examined. RESULTS: As of 2020, the domestic prevalence obtained in this study was 1.84%, increasing annually, and the prevalence increased with age to 4.10% among those over 60. The domestic incidence was 1.57%, increasing annually, and the incidence increased with age to 3.36% for those over 60s. The Gap was 0.27%, showing a steady increase from 2011 to 2020 with a corresponding increase in insurance benefit expenses. CONCLUSION: To fully understand the burden of hearing loss and develop effective prevention and treatment strategies, it is important to measure the Gap between its prevalence and incidence. This Gap means a lot because hearing loss is an irreversible disease. Gap represents patients who have already been diagnosed with hearing loss and are being diagnosed every year, indicating that the number of patients who do not recover is increasing. In other words, the increase in Gap meant that there were many patients who constantly visited the hospital for diagnosis of hearing loss.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

PURPOSE: To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). METHODS: This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24 and 48 weeks. Secondary outcomes included arthroscopic, histological and magnetic resonance imaging assessments at 1 year. RESULTS: Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignment and clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). CONCLUSION: hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. LEVEL OF EVIDENCE: Level II, Prospective Comparative Cohort Study.

Radical-Driven Crystal-Amorphous-Crystal Transition of a Metal-Organic Framework.

Self-assembly-based structural transition has been explored for various applications, including molecular machines, sensors, and drug delivery. In this study, we developed new redox-active metal-organic frameworks (MOFs) called DGIST-10 series that comprise π-acidic 1,4,5,8-naphthalenediimide (NDI)-based ligands and Ni2+ ions, aiming to boost ligand-self-assembly-driven structural transition and study the involved mechanism. Notably, during the synthesis of the MOFs, a single-crystal-amorphous-single-crystal structural transition occurred within the MOFs upon radical formation, which was ascribed to the fact that radicals prefer spin-pairing or through-space electron delocalization by π-orbital overlap. The radical-formation-induced structural transitions were further confirmed by the postsynthetic solvothermal treatment of isolated nonradical MOF crystals. Notably, the transient amorphous phase without morphological disintegration was clearly observed, contributing to the seminal structural change of the MOF. We believe that this unprecedented structural transition triggered by the ligand self-assembly magnifies the structural flexibility and diversity of MOFs, which is one of the pivotal aspects of MOFs.

Herbivory limits success of vegetation restoration globally.

Restoring vegetation in degraded ecosystems is an increasingly common practice for promoting biodiversity and ecological function, but successful implementation is hampered by an incomplete understanding of the processes that limit restoration success. By synthesizing terrestrial and aquatic studies globally (2594 experimental tests from 610 articles), we reveal substantial herbivore control of vegetation under restoration. Herbivores at restoration sites reduced vegetation abundance more strongly (by 89%, on average) than those at relatively undegraded sites and suppressed, rather than fostered, plant diversity. These effects were particularly pronounced in regions with higher temperatures and lower precipitation. Excluding targeted herbivores temporarily or introducing their predators improved restoration by magnitudes similar to or greater than those achieved by managing plant competition or facilitation. Thus, managing herbivory is a promising strategy for enhancing vegetation restoration efforts.

Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample.

OBJECTIVES: We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea. METHODS: In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022. RESULTS: In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%. CONCLUSIONS: The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.

Efficacy of Plant-Made Human Recombinant ACE2 against COVID-19 in a Golden Syrian Hamster Model.

Coronavirus disease 2019 (COVID-19) is a novel infectious respiratory disease caused by SARS-CoV-2. We evaluated the efficacy of a plant-based human recombinant angiotensin-converting enzyme 2 (hrACE2) and hrACE2-foldon (hrACE2-Fd) protein against COVID-19. In addition, we analyzed the antiviral activity of hrACE2 and hrACE2-Fd against SARS-CoV-2 using real-time reverse-transcription PCR and plaque assays. The therapeutic efficacy was detected using the Golden Syrian hamster model infected with SARS-CoV-2. Both hrACE2 and hrACE2-Fd inhibited SARS-CoV-2 by 50% at concentrations below the maximum plasma concentration, with EC50 of 5.8 µg/mL and 6.2 µg/mL, respectively. The hrACE2 and hrACE2-Fd injection groups showed a tendency for decreased viral titers in nasal turbinate tissues on day 3 after virus inoculation; however, this decrease was not detectable in lung tissues. Histopathological examination on day 9 after virus inoculation showed continued inflammation in the SARS-CoV-2 infection group, whereas decreased inflammation was observed in both the hrACE2 and hrACE2-Fd injection groups. No significant changes were observed at other time points. In conclusion, the potential therapeutic efficacy of plant-based proteins, hrACE2 and hrACE2-Fd, against COVID-19 was confirmed in a SARS-CoV-2-inoculated Golden Syrian hamster model. Further preclinical studies on primates and humans are necessary to obtain additional evidence and determine the effectiveness of these therapies.

Epidemiology of idiopathic sudden sensorineural hearing loss in the era of big data.

OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a medical emergency, and delayed treatment can have permanent sequelae. However, the etiology of ISSNHL is diverse and unclear; thus, it is idiopathic. To develop an insight into this condition, patients with ISSNHL must be clearly identified. We propose an operational definition for the unambiguous identification of ISSNHL patients. Patients are identified through suggested definitions, and prevalence and general information are investigated. METHODS: A retrospective study of patients with ISSNHL was performed using the Health Insurance and Review Assessment-National Patient Sample from 2009 to 2016. To present a new operational definition, a systematic review was conducted for studies on ISSNHL from January 2007 to June 2021. After constructing several operant definitions using the conditions that can specify patients with ISSNHL in big data, we compared each definition to propose an operational definition. RESULTS: The important conditions required to classify patients with ISSNHL using big data were the International Classification of Diseases (ICD)-10 code, number of pure tone audiometry (PTA) tests, and whether steroids were prescribed. Among them, those who had undergone PTA tests more than twice could be clearly identified as patients with ISSNHL. CONCLUSION: As the use of big data becomes smoother, research using national medical data is being conducted; however, the results of the studies may vary depending on how a patient with ISSNHL is classified. Clear identification of patients with ISSNHL will be beneficial for better management of this condition.

Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation.

Mutations in DNAJC5/CSPα are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease featuring lysosome-derived autofluorescent storage materials (AFSMs) termed lipofuscin. Functionally, DNAJC5 has been implicated in chaperoning synaptic proteins and in misfolding-associated protein secretion (MAPS), but how DNAJC5 dysfunction causes lipofuscinosis and neurodegeneration is unclear. Here we report two functionally distinct but coupled chaperoning activities of DNAJC5, which jointly regulate lysosomal homeostasis: While endolysosome-associated DNAJC5 promotes ESCRT-dependent microautophagy, a fraction of perinuclear and non-lysosomal DNAJC5 mediates MAPS. Functional proteomics identifies a previously unknown DNAJC5 interactor SLC3A2/CD98hc that is essential for the perinuclear DNAJC5 localization and MAPS but dispensable for microautophagy. Importantly, uncoupling these two processes, as seen in cells lacking SLC3A2 or expressing ANCL-associated DNAJC5 mutants, generates DNAJC5-containing AFSMs resembling NCL patient-derived lipofuscin and induces neurodegeneration in a Drosophila ANCL model. These findings suggest that MAPS safeguards microautophagy to avoid DNAJC5-associated lipofuscinosis and neurodegeneration.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AFSM: autofluorescent storage materials; ANCL: adult neuronal ceroid lipofuscinosis; Baf. A1: bafilomycin A1; CLN: ceroid lipofuscinosis neuronal; CLU: clusterin; CS: cysteine string domain of DNAJC5/CSPα; CUPS: compartment for unconventional protein secretion; DN: dominant negative; DNAJC5/CSPα: DnaJ heat shock protein family (Hsp40) member C5; eMI: endosomal microautophagy; ESCRT: endosomal sorting complex required for transport; GFP: green fluorescent protein; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INCL: infant neuronal ceroid lipofuscinosis; JNCL: juvenile neuronal ceroid lipofuscinosis; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LAPTM4B: lysosomal protein transmembrane 4 beta; LN: linker domain of DNAJC5/CSPα; MAPS: misfolding-associated protein secretion; mCh/Ch: mCherry; mCi/Ci: mCitrine; MTOR: mechanistic target of rapamycin kinase; NCL: neuronal ceroid lipofuscinosis; PPT1: palmitoyl-protein thioesterase 1; PQC: protein quality control; SBP: streptavidin binding protein; SGT: small glutamine-rich tetratricopeptide repeat; shRNA: short hairpin RNA; SLC3A2/CD98hc: solute carrier family 3 member 2; SNCA/α-synuclein: synuclein alpha; TMED10: transmembrane p24 trafficking protein 10; UV: ultraviolet; VPS4: vacuolar protein sorting 4 homolog; WT: wild type.

Association of dietary factors with noise-induced hearing loss in Korean population: A 3-year national cohort study.

Noise-induced hearing loss (NIHL) is a hearing impairment (HI) caused by various clinical factors. Identifying the relationship between NIHL and nutrient consumption could help in reducing the prevalence of hearing loss. The aim of this study was to analyze the relationship between NIHL and dietary factors using data of the Korea National Health and Nutrition Examination survey (KNHANES). The data were collected from The Fifth KNHANES 2010-2012. The survey was taken by a total of 10,850 participants aged 20-65 years. Air conduction audiometry was measured at 500, 1000, 2000, and 4000 Hz in both ears. Metabolic syndrome, noise exposure, alcohol consumption, smoking, income level, marital status, and nutritional intake were evaluated. The differences between non-HI and HI participants in the noise-exposed group showed statistically significant differences in age, sex, marital and smoking status, alcohol consumption, and fasting glucose and triglyceride levels (p<0.05). In a multiple regression analysis of the noise-exposed group, age showed a significant association with HI (OR: 0.604; 95% CI: 0.538-0.678) after adjusting for confounders. In multivariate analysis for dietary factors affecting HI in noise-exposed groups, retinol (OR: 1.356; 95% CI: 1.068-1.722), niacin (OR: 1.5; 95% CI: 1.022-2.201), and carbohydrates (OR: 0.692; 95% CI: 0.486-0.985) showed a significant association with NIHL. Age was identified as the only factor significantly affecting NIHL. When the dietary factors of the noise-exposed group were analyzed, high intake of niacin and retinol and low intake of carbohydrates appeared to reduce the risk of hearing loss.

π-Stacks of radical-anionic naphthalenediimides in a metal-organic framework.

Radical-ionic metal-organic frameworks (MOFs) have unique optical, magnetic, and electronic properties. These radical ions, forcibly formed by external stimulus-induced redox processes, are structurally unstable and have short radical lifetimes. Here, we report two naphthalenediimide-based (NDI-based) Ca-MOFs: DGIST-6 and DGIST-7. Neutral DGIST-6, which is generated first during solvothermal synthesis, decomposes and is converted into radical-anionic DGIST-7. Cofacial (NDI)2•- and (NDI)22- dimers are effectively stabilized in DGIST-7 by electron delocalization and spin-pairing as well as dimethylammonium counter cations in their pores. Single-crystal x-ray diffractometry was used to visualize redox-associated structural transformations, such as changes in centroid-to-centroid distance. Moreover, the unusual rapid reduction of oxidized DGIST-7 into the radical anion upon infrared irradiation results in effective and reproducible photothermal conversion. This study successfully illustrated the strategic use of in situ prepared cofacial ligand dimers in MOFs that facilitate the stabilization of radical ions.

Supplementation with Vitis vinifera Jingzaojing Leaf and Shoot Extract Improves Exercise Endurance in Mice.

Switching myofibers from the fast-glycolytic type to the slow-oxidative type is associated with an alleviation of the symptoms associated with various cardiometabolic diseases. This study investigates the effect of Vitis vinifera Jingzaojing leaf and shoot extract (JLSE), which is rich in phenolic compounds, on the regulation of skeletal muscle fiber-type switching, as well as the associated underlying mechanism. Male C57BL/6N mice were supplemented orally with vehicle or JLSE (300 mg/kg) and subjected to treadmill exercise training. After four weeks, mice in the JLSE-supplemented group showed significantly improved exercise endurance and mitochondrial oxidative capacity. JLSE supplementation increased the expression of sirtuin 6 and decreased Sox6 expression, thereby elevating the number of mitochondria and encouraging fast-to-slow myofiber switching. The results of our experiments suggest that JLSE supplementation reprograms myofiber composition to favor the slow oxidative type, ultimately enhancing exercise endurance.

Nationwide changes in physical activity, nutrient intake, and obesity in South Korea during the COVID-19 pandemic era.

Background: This study aimed to examine changes in obesity rates and obesity-related factors during the COVID-19 pandemic compared to a previous period. Methods: An ecological time-series study was designed using the Korean National Health and Nutritional Examination Survey (KNHANES) database from 2014 to 2020. The expected values of obesity rate, physical activity rate, and nutrient intake for 2020 were estimated. The differences between the predicted and actual values for 2020 were also examined. In addition, a multiple logistic regression model was used to examine the changes in obesity and physical activity rates in 2020 compared to 2019. Results: The actual obesity rates in 2020 were higher, and the walking and aerobic physical activity rates were lower than the predicted values for the same year. However, the actual resistance training rates in 2020 were higher and the total energy intake was lower than the predicted values for 2020. In the multiple logistic regression model, the odds ratios for obesity, aerobic physical activity, and walking among men in 2020 were 1.29 (95% CI: 1.08 to 1.55), 0.86 (0.74 to 1.01), and 0.84 (0.73 to 0.97), respectively, compared to those in 2019. However, there were no significant differences between the values for women in 2020 and 2019. Conclusions: This study suggests that the male obesity rate in Korea has significantly increased during the COVID-19 epidemic, mainly due to a decrease in physical activity.

Studying Unconventional Secretion of Misfolded Proteins in Cultured Cells and Primary Neurons.

Protein misfolding poses a significant threat to the fitness of eukaryotic cells, particularly for neurons facing environmental stress. To effectively triage and remove defective and unwanted proteins, cells have evolved diverse protein quality control (PQC) mechanisms relying on proteasome- and endolysosome-mediated degradation systems. Defects in PQC functions are linked to various human diseases including many aging-associated neurodegenerative diseases. Misfolding-associated protein secretion (MAPS) is a recently reported PQC mechanism that eliminates misfolded cytosolic proteins by an unconventional secretory pathway using an endo-vesiclular network. This process implicates DNAJC5, a chaperone that escorts misfolded cargos to intracellular vesicles to facilitate their secretion. Cargos of DNAJC5 include Parkinson's and Alzheimer's disease-associated proteins known to undergo cell-to-cell transmission during disease progression. Thus, elucidating how these proteins are secreted may reveal novel therapeutic targets for these diseases. Here we describe a collection of methods used to detect either the basal or induced secretion of misfolded proteins from cell lines and cultured primary neurons.

Nonequilibrium Charge-Density-Wave Melting in 1T-TaS2 Triggered by Electronic Excitation: A Real-Time Time-Dependent Density Functional Theory Study.

Ultrafast charge transfer in van der Waals (vdW) heterostructures enables efficient control of two-dimensional material properties through strong optical absorption and subsequent carrier transfer. Here, using real-time time-dependent density functional theory coupled to molecular dynamics, we investigated the nonequilibrium dynamics of charge-density-wave (CDW) melting in 1T-TaS2 triggered by ultrafast charge transfer in 1T-TaS2/MoSe2 or WSe2 heterostructures. Despite the fast and sufficient charge transfer from the MoSe2 (or WSe2) "electrode" to the 1T-TaS2 layer, the electronic excitation of the vdW heterostructure does not lead to the nonthermal CDW transition of 1T-TaS2. Instead, the TaS2 lattice is heated by carrier-lattice scattering, leading to thermal CDW melting at high ionic temperatures. The lack of nonthermal melting follows from the fact that the time scale of carrier recombination in 1T-TaS2 is similar to or faster than that of charge transfer. These findings provide physical insights into understanding the CDW melting dynamics in vdW heterostructures under nonequilibrium conditions.

IgM+ and IgM- memory B cells represent heterogeneous populations capable of producing class-switched antibodies and germinal center B cells upon rechallenge with P. yoelii.

Memory B cells (MBCs) are essential for maintaining long-term humoral immunity to infectious organisms, including Plasmodium. MBCs are a heterogeneous population whose function can be dictated by isotype or expression of particular surface proteins. Here, aided by antigen-specific B-cell tetramers, MBC populations were evaluated to discern their phenotype and function in response to infection with a nonlethal strain of P. yoelii. Infection of mice with P. yoelii 17X resulted in 2 predominant MBC populations: somatically hypermutated isotype-switched (IgM- ) and IgM+ MBCs that coexpressed CD73 and CD80 that produced antigen-specific antibodies in response to secondary infection. Rechallenge experiments indicated that IgG-producing cells dominated the recall response over the induction of IgM-secreting cells, with both populations expanding with similar timing during the secondary response. Furthermore, using ZsGreen1 expression as a surrogate for activation-induced cytidine deaminase expression alongside CD73 and CD80 coexpression, ZsGreen1+ CD73+ CD80+ IgM+ , and IgM- MBCs gave rise to plasmablasts that secreted Ag-specific Abs after adoptive transfer and infection with P. yoelii. Moreover, ZsGreen1+ CD73+ CD80+ IgM+ and IgM- MBCs could differentiate into B cells with a germinal center phenotype after adoptive transfer. A third population of B cells (ZsGreen1- CD73- CD80- IgM- ) that is apparent after infection responded poorly to reactivation in vitro and in vivo, indicating that these cells do not represent a canonical population of MBCs. Together these data indicated that MBC function is not defined by immunoglobulin isotype, nor does coexpression of key surface markers limit the potential fate of MBCs after recall.

Safeguarding Lysosomal Homeostasis by DNAJC5/CSPα-Mediated Unconventional Protein Secretion and Endosomal Microautophagy.

Neuronal ceroid lipofuscinosis (NCL) is a collection of genetically inherited neurological disorders characterized by vision loss, seizure, brain death, and premature lethality. At the cellular level, a key pathologic hallmark of NCL is the build-up of autofluorescent storage materials (AFSM) in lysosomes of both neurons and non-neuronal cells. Molecular dissection of the genetic lesions underlying NCLs has shed significant insights into how disruption of lysosomal homeostasis may lead to lipofuscin accumulation and NCLs. Intriguingly, recent studies on DNAJC5/CSPα, a membrane associated HSC70 co-chaperone, have unexpectedly linked lipofuscin accumulation to two intimately coupled protein quality control processes at endolysosomes. This review discusses how deregulation of unconventional protein secretion and endosomal microautophagy (eMI) contributes to lipofuscin accumulation and neurodegeneration.