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Abstract Single-cell technologies have enhanced comprehensive knowledge regarding the human brain by facilitating an extensive transcriptomic census across diverse brain regions. Nevertheless, understanding the cellular and temporal specificity of neurological disorders remains ambiguous due to developmental variations. To address this gap, we illustrated the dynamics of disorder risk gene expression under development by integrating multiple single-cell RNA sequencing datasets. We constructed a comprehensive single-cell atlas of the developing human brain, encompassing 393,060 single cells across diverse developmental stages. Temporal analysis revealed the distinct expression patterns of disorder risk genes, including those associated with autism, highlighting their temporal regulation in different neuronal and glial lineages. We identified distinct neuronal lineages that diverged across developmental stages, each exhibiting temporal-specific expression patterns of disorder-related genes. Lineages of nonneuronal cells determined by molecular profiles also showed temporal-specific expression, indicating a link between cellular maturation and the risk of disorder. Furthermore, we explored the regulatory mechanisms involved in early brain development, revealing enriched patterns of fetal cell types associated with neuronal disorders indicative of the prenatal stage’s influence on disease determination. Our findings facilitate unbiased comparisons of cell type‒disorder associations and provide insight into dynamic alterations in risk genes during development, paving the way for a deeper understanding of neurological disorders.

Abstract Osteoarthritis (OA) is a degenerative disease of the joints, prevalent worldwide. Polydeoxyribonucleotide (PDRN) is used for treating knee OA. However, the role of PDRN in IL-1β-induced inflammatory responses in human bone marrow-derived mesenchymal stem cells (hBMSCs) remains unknown. Here, we investigated the role of PDRN in IL-1β-induced impairment of chondrogenic differentiation in hBMSCs. hBMSCs treated with PDRN showed a large micromass, enhanced safranin O and alcian blue staining intensity, and increased expression of chondrogenic genes in IL-1β-induced inflammatory responses, in addition to regulation of catabolic and anabolic genes. In addition, PDRN treatment suppressed the expression of inflammatory cytokines and mitigated IL-1β-induced apoptosis in hBMSCs. Mechanistically, PDRN treatment increased the formation of cyclic adenosine monophosphate (cAMP) and upregulated the phosphorylation of cAMP-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) through the adenosine A2A receptor in hBMSCs and thus blocked the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Thus, IL-1β-induced expression of inflammatory cytokines in hBMSCs was directly reduced by adenosine A2A receptor activation. Based on our results, we suggest that PDRN may be a promising MSC-based therapeutic agent for OA.

Abstract While obesity, rapid weight loss, and sedentary lifestyles contribute to gallstones, the impacts of long-term weight patterns and physical activity on gallstone risk have not been extensively studied at the population level. Using Korea’s population-based health database, we created a cohort of 5,062,154 subjects who received over five consecutive biannual health check-ups from 2002 to 2018. Gallstone risk was calculated using hazard ratios (HRs) based on weight patterns (gain, loss, and cycling) and physical activity. Adjustments were made for covariates, such as body mass index (BMI), waist circumference, diabetes, and life style factors. Subgroup analysis was performed by sex and age groups ( 20% weight loss, 1.13 (0.96–1.33) for > 20% weight gain, 1.04 (1.02–1.06) for weight cycling, 1.03 (1.01–1.05) for 5–20% weight gain, and 1.02 (1.00–1.04) for 5–20% weight loss. Risk increased with weight loss or gain in underweight or overweight BMI categories, respectively, and in any weight change for normal BMI. Males and older individuals had higher risks with weight loss, while females and younger individuals had higher risks with weight gain. Weight cycling increased risk for both sexes. Regular physical activity reduced gallstone risk in weight changers to levels similar to weight maintainers, with the highest reduction in those with > 20% weight gain (61%) and the lowest in weight cycling (1%). The risks of gallstones associated with weight gain, loss, or cycling can be mitigated by regular physical activity. The risks vary by sex and age.

Background While inhalation therapy efficacy hinges on attaining proper peak inspiratory flow rate (PIFR), the prevalence of inappropriate PIFR among patients with chronic obstructive pulmonary disease (COPD) remains unstudied in Korea. This study aimed to assess the prevalence of inappropriate PIFR, its correlation with COPD assessment test (CAT) scores, and factors associated with suboptimal PIFR. Methods We enrolled 108 patients with COPD who had been using the same inhaler for at least 1 year without exacerbations. PIFR was measured using an inspiratory flow meter (In-Check DIAL G16). Demographic, clinical, pulmonary function, and CAT score data were collected. Inappropriate was defined as PIFR 90 L/min for aerosol device users. Results The cohort comprised 87 (80.6%) men, mean age 71.0±8.5 years, with mean post-bronchodilator forced expiratory volume in 1 second of 69.1%±1.8% predicted. Twenty-nine (26.9%) used aerosol devices only, 76 (70.4%) used DPIs only, and three (2.8%) used both. Inappropriate PIFRs were found in 17.2% of aerosol device users, and 42.1% of DPI users. CAT scores were significantly higher in the inappropriate PIFR group than in the appropriate PIFR group (11.2±7.7 vs. 7.5±4.9, p=0.003). In DPI users, female, shorter height, lower body weight and maximal voluntary ventilation (MVV) were associated with inappropriate PIFR. Conclusion The prevalence of inappropriate PIFR among patients with COPD is 17.2% for aerosol device users, and 42.1% for DPI users. Suboptimal PIFR correlates with female gender, shorter stature, lower weight and MVV in DPI users.

Abstract Low-level somatic mutations in the human brain are implicated in various neurological disorders. The contribution of low-level brain somatic mutations to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth of 559.3x in 181 cortical, cerebellar, and peripheral tissue samples to identify brain somatic single nucleotide variants (SNVs) in 24 ASD subjects and 31 controls. We detected ~2.4 brain somatic SNVs per exome per single brain region, with a variant allele frequency (VAF) as low as 0.3%. The mutational profiles, including the number, signature, and type, were not significantly different between the ASD patients and controls. Intriguingly, when considering genes with low-level brain somatic SNVs and ASD risk genes with damaging germline SNVs together, the merged set of genes carrying either somatic or germline SNVs in ASD patients was significantly involved in ASD-associated pathophysiology, including dendrite spine morphogenesis (p = 0.025), mental retardation (p = 0.012), and intrauterine growth retardation (p = 0.012). Additionally, the merged gene set showed ASD-associated spatiotemporal expression in the early and mid-fetal cortex, striatum, and thalamus (all p

Abstract Background Ischemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes. Methods Researchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1. Results Out of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13–75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14–3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23–1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30–1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73–1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61–1.56, P = 0.93). Conclusions It could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future. Systematic review registration PROSPERO CRD42022336565.

Gastritis is a disease characterized by inflammation of the gastric mucosa. It is very common and has various classification systems such as the updated Sydney system. As there is a lot of evidence that Helicobacter pylori infection is associated with the development of gastric cancer and that gastric cancer can be prevented by eradication, H. pylori gastritis has been emphasized recently. The incidence rate of gastric cancer in Korea is the highest in the world, and due to the spread of screening endoscopy, atrophic gastritis and intestinal metaplasia are commonly diagnosed in the general population. However, there have been no clinical guidelines developed in Korea for these lesions. Therefore, this clinical guideline has been developed by the Korean College of Helicobacter and Upper Gastrointestinal Research for important topics that are frequently encountered in clinical situations related to gastritis. Evidence-based guidelines were developed through systematic review and de novo processes, and eight recommendations were made for eight key questions. This guideline needs to be periodically revised according to the needs of clinical practice or as important evidence about this issue is published in the future.

ABSTRACT This study addresses the gap in translatable in vitro models for investigating Enterohemorrhagic E. coli (EHEC) infections, particularly relevant to both canine and human health. EHEC is known to induce acute colitis in dogs, leading to symptoms like hemorrhagic diarrhea and hemolytic uremic syndrome, similar to those observed in humans. However, understanding the pathophysiology and developing treatment strategies have been challenging due to the lack of effective models that replicate the clinical disease caused by EHEC in both species. Our approach involved the development of colonoid-derived monolayers using intestinal tissues from healthy, client-owned dogs. These monolayers were exposed to EHEC, and the impact of EHEC was assessed through several techniques, including trans-epithelial electrical resistance (TEER) measurement, immunofluorescence staining for junction proteins and mucus, and scanning electron microscopy for morphological analysis. Modified culture with saline, which was intended to prevent bacterial overgrowth, maintained barrier integrity and cell differentiation. EHEC infection led to significant decreases in TEER and ZO-1 expression, but not in E-cadherin levels or mucus production. In addition, EHEC elicited a notable increase in tumor necrosis factor-alpha production, highlighting its distinct impact on canine intestinal epithelial cells compared to non-pathogenic E. coli. These findings closely replicate in vivo observations in dogs and humans with EHEC enteropathy, validating the canine colonoid-derived monolayer system as a translational model to study host-pathogen interactions in EHEC and potentially other clinically significant enteric pathogens.IMPORTANCEThis study develops a new model to better understand Enterohemorrhagic E. coli (EHEC) infections, a serious bacterial disease affecting both dogs and humans, characterized by symptoms such as hemorrhagic diarrhea and hemolytic uremic syndrome. Traditional research models have fallen short of mimicking how this disease manifests in patients. Our research used intestinal tissues from healthy dogs to create layers of cells, known as colonoid-derived monolayers, which we then exposed to EHEC. We assessed the damage caused by the bacteria using several techniques, observing significant changes similar to those seen in actual cases of the disease. The model proved effective in replicating the interaction between the host and the pathogen, marking an important step toward understanding EHEC’s effects and developing treatments. This canine colonoid-derived monolayer system not only bridges a crucial gap in current research but also offers a promising platform for studying other enteric pathogens affecting both canine and human health.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Abstract Recent growth in space systems has seen increasing capabilities packed into smaller and lighter Earth observation and deep space mission spacecraft. Phase-change materials (PCMs) are nonvolatile, reconfigurable, fast-switching, and have recently shown a high degree of space radiation tolerance, thereby making them an attractive materials platform for spaceborne photonics applications. They promise robust, lightweight, and energy-efficient reconfigurable optical systems whose functions can be dynamically defined on-demand and on-orbit to deliver enhanced science or mission support in harsh environments on lean power budgets. This comment aims to discuss the recent advances in rapidly growing PCM research and its potential to transition from conventional terrestrial optoelectronics materials platforms to versatile spaceborne photonic materials platforms for current and next-generation space and science missions. Materials International Space Station Experiment-14 (MISSE-14) mission-flown PCMs outside of the International Space Station (ISS) and key results and NASA examples are highlighted to provide strong evidence of the applicability of spaceborne photonics.

This study assessed risk factors for blood transfusion after Cesarean section in patients with partial placenta previa. We retrospectively reviewed the medical records of 149 patients who underwent Cesarean sections for partial placenta previa between January 2010 and October 2021. Clinical characteristics were compared between the two groups: the blood transfusion group (n=22), defined as patients who received a blood transfusion during surgery or within 24 hours after surgery, and the non-blood transfusion group (n=127), which included other patients. Multivariable logistic regression analysis identified two risk factors independently associated with blood transfusion: antenatal hemorrhage (adjusted odds ratio [aOR], 16.283; 95% confidence interval [CI], 4.405-60.190; P

Metastasis to the penis from RCC or any other primary cancer site is unusual; when it does occur, it often involves multiple organs. A 75-year-old man presented with penile pain and swelling. Three months earlier, he had open radical nephrectomy with thrombectomy and was diagnosed with clear-cell RCC with tumor thrombosis in the IVC. The follow-up imaging indicated metastasis in the penis, prompting a total penectomy due to worsening pain. The excised mass displayed features consistent with metastatic RCC. This case underscores the need to consider rare metastatic sites, such as metastasis of RCC to the penis, in RCC patients.

Multiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not been identified or the role of genetic variants in mild cases is less understood. Genetic variant testing in mild cases is necessary to provide information on prognosis and risk of occurrence. In this study, we report two sibling patients who were 5 years 9 months old and 3 years 3 months old and presented to the hospital due to developmental delay. Clinical assessment and chromosomal microarray analysis were performed. The patients were diagnosed with mild intellectual disability (ID) and borderline intellectual functioning (BIF). Genetic analysis identified a loss of 12p11.22, including the OVCH1-AS1, OVCH1, and TMTC1 genes, which was the only variant that occurred in both sisters. Identical variants were found in their father with probable BIF. Neither patient presented any brain structural abnormalities or dysmorphism, and no exogenous factors or parenting problems were reported. Thus, loss of 12p11.22 may be associated with our patients’ cognitive impairment. The OVCH1, OVCH1-AS1 and TMTC1 variants identified in this study are the most likely disease-causing genes in the sisters. Our findings may expand as yet limited knowledge on mild ID and BIF causative variants, which would further support the diagnosis even if the severity is mild.

Abstract We aimed to evaluate the incidence and risk of pancreatic cancer (PC) in pancreatitis. We identified patients with acute pancreatitis (AP) (n = 225,811, 50.0%) and chronic pancreatitis (CP) (n = 225,685, 50.0%) from Korean population-based data and matched them with age- and sex-matched controls (n = 4,514,960). We analyzed the incidence and adjusted hazard ratios (aHRs) of PC among patients followed for more than 2 years or 5 years, and assessed risk changes over time in single episode of AP (SAP), recurrent AP (RAP), CP with AP, and CP without AP groups. We also performed subgroup analysis for both sexes. The incidences (per 104 person-years) and risks (aHR) of PC were higher in the RAP (12.69, 5.00) or CP with AP (12.12, 5.74) groups compared to the SAP (2.31, 1.32) or CP without AP (2.28, 1.57) groups. The risks of PC decreased over time, however, the risk of PC remained elevated in the RAP and CP with AP groups for more than 8 years. Females with RAP, SAP, and CP with AP had higher risks of PC than males. The risk of PC is higher and persists for longer duration in patients with RAP and CP with AP compared to those with SAP or CP without AP.

Abstract Pregnancy imposes a substantial metabolic burden on women, but little is known about whether or how multiple pregnancies increase the risk of maternal postpartum diabetes. In this study, we assessed the metabolic impact of multiple pregnancies in humans and in a rodent model. Mice that underwent multiple pregnancies had increased adiposity, but their glucose tolerance was initially improved compared to those of age-matched virgin mice. Later, however, insulin resistance developed over time, but insulin secretory function and compensatory pancreatic β cell proliferation were impaired in multiparous mice. The β cells of multiparous mice exhibited aging features, including telomere shortening and increased expression of Cdkn2a. Single-cell RNA-seq analysis revealed that the β cells of multiparous mice exhibited upregulation of stress-related pathways and downregulation of cellular respiration- and oxidative phosphorylation-related pathways. In humans, women who delivered more than three times were more obese, and their plasma glucose concentrations were elevated compared to women who had delivered three or fewer times, as assessed at 2 months postpartum. The disposition index, which is a measure of the insulin secretory function of β cells, decreased when women with higher parity gained body weight after delivery. Taken together, our findings indicate that multiple pregnancies induce cellular stress and aging features in β cells, which impair their proliferative capacity to compensate for insulin resistance.

Abstract Aim This study aims to investigate the effect and methods of cryotherapy in reducing swelling after total knee arthroplasty. Design Systematic review. Methods We searched PubMed, Embase, CINAHL, Cochrane Library, KoreaMed, KERIS and National Science Digital Library for randomized controlled trials on 19 August 2021. This systematic review was conducted according to the PRISMA 2009 checklist. Results A total of eight randomized controlled trials were systematically reviewed to determine the effect and methods of cryotherapy on reducing postoperative swelling. The effects were not significantly different in six studies. Application time per cryotherapy session was 10–20 min when using an ice pack and up to 48 h when using an automated device. The duration ranged from 2 days to 1 week or until discharge, and the frequency varied from 2 to 72 times per day.

ABSTRACTThis study aimed to compare phytochemical content and antioxidant activities of eight diverse citrus cultivars grown in Jeju Island depending on their harvest time owing to their health benefits. Plant peels, flesh, and leaves were extracted, and their flavonoid contents were measured by HPLC. Flavonoid levels were high in peel followed by leaves and juices. It was highest in immature fruits and rapidly declined during ripening. While total phenolic content in all citrus peels and fleshes reduced during ripening, those of leaves did not significantly decrease. Antioxidant activity matched the total phenolic content. This indicates that immature citrus tissues exhibited the highest flavonoid and phenolic content with high antioxidant activity and can be potentially employed as a readily accessible natural antioxidant source.

Abstract Two-photon microscopy (TPM) is an attractive biomedical imaging method due to its large penetration depth and optical sectioning capability. In particular, label-free autofluorescence imaging offers various advantages for imaging biological samples. However, relatively low intensity of autofluorescence leads to low signal-to-noise ratio (SNR), causing practical challenges for imaging biological samples. In this study, we present TPM using a pulse picker to utilize low pulse repetition rate of femtosecond pulsed laser to increase the pulse peak power of the excitation source leading to higher emission of two-photon fluorescence with the same average illumination power. Stronger autofluorescence emission allowed us to obtain higher SNR images of arterial and liver tissues. In addition, by applying the time gating detection method to the pulse signals obtained by TPM, we were able to significantly reduce the background noise of two-photon images. As a result, our TPM system using the pulsed light source with a 19 times lower repetition rate allowed us to obtain the same SNR image more than 19 times faster with the same average power. Although high pulse energy can increase the photobleaching, we also observed that high-speed imaging with low total illumination energy can mitigate the photobleaching effect to a level similar to that of conventional illumination with a high repetition rate. We anticipate that this simple approach will provide guidance for SNR enhancement with high-speed imaging in TPM as well as other nonlinear microscopy.

Objective To determine correlations of alternation motor rate (AMR), sequential motor rate (SMR), and maximum phonation time (MPT) with the severity of dysphagia in subacute stroke patients. Methods This was a retrospective chart review study. Data of 171 subacute stroke patients were analyzed. Patient’s AMR, SMR, and MPT data were collected from their language evaluations. Video fluoroscopic swallowing study (VFSS) was done. Data of dysphagia scales including penetration-aspiration scale (PAS), American Speech-Language-Hearing Association National Outcomes Measurement System (ASHA-NOMS) scale, clinical dysphagia scale (CDS), and videofluoroscopic dysphagia scale (VDS) were obtained. AMR, SMR, and MPT were compared between a non-aspirator group and an aspirator group. Correlations of AMR, SMR, and MPT with dysphagia scales were analyzed. Results AMR ("ka"), SMR, and modified Rankin Scale were significant associated factors between non-aspirator group and aspirator group, while AMR ("pa"), AMR ("ta"), and MPT were not. AMR, SMR, and MPT showed significant correlations with PAS score, ASHA-NOMS scale, CDS, VDS oral, and VDS pharyngeal scores. The cut-off value for distinguishing non-aspirator group and aspiration group was 18.5 for AMR ("ka") (sensitivity of 74.4%, specificity of 70.8%) and 7.5 for SMR (sensitivity of 89.9%, specificity of 61.0%). AMR and SMR were significantly lower in before-swallow aspiration group. Conclusion Articulatory diadochokinetic tasks that can be easily performed at the bedside would be particularly helpful in determining the oral feeding possibility of subacute stroke patients who cannot undergo VFSS, which is the gold standard for dysphagia assessment.

Adrenal corticosteroid biosynthesis dysregulation can give rise to various pathological conditions, such as Cushing's syndrome, a disorder characterized by the sustained and excessive production of cortisol. Despite the development of several classes of steroidogenesis inhibitors to treat human diseases associated with cortisol overproduction, their use is limited by insufficient efficacy, adverse effects, and/or tolerability. Recently, we identified a series of benzimidazolylurea derivatives, including the representative compound CJ28, as novel cortisol biosynthesis inhibitors [1]. They significantly inhibited both basal and stimulated production of cortisol in NCI-H295R cells, a human adrenocarcinoma cell line. The inhibitory effects were attributed to both attenuated steroidogenesis and de novo cholesterol biosynthesis. Here, we provide transcriptomic (RNA-seq) data from adrenal cell cultures in response to treatment with either CJ28 or metyrapone (MET), an inhibitor of 11β-hydroxylase). Total RNA was extracted from the cells treated with vehicle (0.1% DMSO), CJ28 (30 µM), or MET (30 µM) for 24 h. Primary sequence data were acquired using paired-end sequencing on an Illumina NovaSeq 6000 platform. The raw RNA-seq data have been deposited in the Gene Expression Omnibus (GEO) database (GSE236435). This dataset is a useful resource for providing valuable information on the gene expression networks underlying adrenocortical steroidogenesis.

Owing to their unique tunable optical properties, chalcogenide phase change materials are increasingly being investigated for optics and photonics applications. However, in situ characterization of their phase transition characteristics is a capability that remains inaccessible to many researchers. Herein, a multifunctional silicon microheater platform capable of in situ measurement of structural, kinetic, optical, and thermal properties of these materials is introduced. The platform can be fabricated leveraging industry‐standard silicon foundry manufacturing processes. This platform is fully open‐sourced, including complete hardware design and associated software codes.

Objective To investigate the relationship between Trunk Impairment Scale (TIS) and lumbar spine bone mineral density (BMD) in subacute stroke patients. Methods Twenty-three subacute male stroke patients under the age of 65 were prospectively enrolled to exclude both postmenopausal and senile effects on BMD. The TIS, Berg Balance Scale, the Korean version of the Modified Barthel Index, and manual muscle test were measured at admission and 3 months after stroke onset. BMD of the bilateral lower extremities and lumbar vertebrae was measured by dual-energy X-ray absorptiometry 3 months after stroke onset. Results TIS at baseline (TIS_B) and TIS at 3 months after stroke (TIS_3m) showed significant correlations with lumbar BMD (TIS_B, r=0.522; TIS_3m, r=0.517). Through multiple regression analysis, the TIS_B was associated with lumbar BMD (adjusted R2=0.474). However, BMD of the bilateral lower extremities was not correlated with any clinical measurements except body mass index. Conclusion We found a relationship between TIS_B and lumbar BMD in subacute young male stroke patients. Stroke patients with poor trunk control in the early subacute stage would have low BMD of vertebral bones at 3 months. The TIS can be useful for estimating bone fragility in the lumbar vertebrae of subacute stroke patients.

Abstract Polydeoxyribonucleotide (PDRN) is an agonist that selectively stimulates adenosine A2A receptor (ADORA2A), which suppresses inflammatory responses. Ischemia/reperfusion (I/R) injury plays a major role in the pathogenesis of ischemic stroke by inducing neuroinflammation. Therefore, this study aimed to investigate the therapeutic effects of PDRN in an in vitro I/R injury model. The in vitro model was established with differentiated Neuro-2a cells under oxygen and glucose deprivation condition. The cells were treated with PDRN for 24 h under reoxygenation condition. As the results of RNA-seq transcriptome analysis, CSF1, IL-6, PTPN6, RAC2, and STAT1 were identified of its relation to the effect of PDRN on inflammatory responses in the model. To further investigate therapeutic effects of PDRN, RT-qPCR, western blotting, LDH assay, and TUNEL assay were performed. PDRN significantly reversed the expression of genes and proteins related to inflammatory responses. The elevated ADORA2A expression by PDRN treatment downregulated JAK/STAT pathway in the model. Furthermore, PDRN inhibited neuronal cell death in the model. Consequently, our results suggested that PDRN alleviated inflammatory responses through inhibition of JAK/STAT pathway by mediating ADORA2A expression and inhibited neuronal cell death in the model. These results provide significant insights into potential therapeutic approaches involving PDRN treatment for I/R injury.

Small mammals, such as rodents and shrews, are natural reservoir hosts of zoonotic diseases, including parasitic protozoa. To assess the risk of rodent-borne parasitic protozoa in the Republic of Korea (ROK), this study investigated the status of parasitic protozoa, namely Trypanosoma, Babesia, and Theileria, in small mammals. In total, 331 blood samples from small mammals were analyzed for parasites using PCR and sequenced. Samples were positive for Trypanosoma grosi (23.9%; n = 79) and Babesia microti (10%; n = 33) but not Theileria. Small mammals from Seogwipo-si showed the highest infection rate of T. grosi (48.4%), while the highest B. microti infection rate was observed in those from Gangneung-si (25.6%). Sequence data revealed T. grosi to be of the AKHA strain. Phylogenetic analysis of B. microti revealed the US and Kobe genotypes. B. microti US-type–infected small mammals were detected throughout the country, but the Kobe type was only detected in Seogwipo-si. To our knowledge, this is the first nationwide survey that confirmed T. grosi and B. microti infections at the species level in small mammals in the ROK and identified the Kobe type of B. microti. These results provide valuable information for further molecular epidemiological studies on these parasites.

Background Current guidelines on the management of chronic cough do not provide recommendations for the operation of specialist cough clinics. The objective of the present study was to develop expert consensus on goals and standard procedures for specialist cough clinics. Methods We undertook a modified Delphi process, whereby initial statements proposed by experts were categorised and presented back to panellists over two ranking rounds using an 11-point Likert scale to identify consensus. Results An international panel of 57 experts from 19 countries participated, with consensus reached on 15 out of 16 statements, covering the aims, roles and standard procedures of specialist cough clinics. Panellists agreed that specialist cough clinics offer optimal care for patients with chronic cough. They also agreed that history taking should enquire as to cough triggers, cough severity rating scales should be routinely used, and a minimum of chest radiography, spirometry and measurements of type 2 inflammatory markers should be undertaken in newly referred patients. The importance of specialist cough clinics in promoting clinical research and cough specialty training was acknowledged. Variability in healthcare resources and clinical needs between geographical regions was noted. Conclusions The Delphi exercise provides a platform and guidance for both established cough clinics and those in planning stages.

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation of non-CCS donor HIOs and inhibition of 5HT production in the CCS HIOs resulted in decreased proliferation, suggesting a link between local epithelial 5HT production and control of epithelial stem cell proliferation. This link was confirmed in genetically engineered HIOs with an increased number of enteroendocrine cells. This work provides a new mechanism to explain the pathogenesis of CCS and illustrates the important contribution of HIO cultures to understanding disease etiology and in the identification of novel therapies. Our work demonstrates the principle of using organoids for personalized medicine and sheds light on how intestinal hormones can play a role in intestinal epithelial proliferation.

IntroductionThe emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has caused unprecedented health and socioeconomic crises, necessitating the immediate development of highly effective neutralizing antibodies. Despite recent advancements in anti-SARS-CoV-2 receptor-binding domain (RBD)-specific monoclonal antibodies (mAbs) derived from convalescent patient samples, their efficacy against emerging variants has been limited. In this study, we present a novel dual-targeting strategy using bispecific antibodies (bsAbs) that specifically recognize both the SARS-CoV-2 RBD and fusion peptide (FP), crucial domains for viral attachment to the host cell membrane and fusion in SARS-CoV-2 infection. MethodsUsing phage display technology, we rapidly isolated FP-specific mAbs from an established human recombinant antibody library, identifying K107.1 with a nanomolar affinity for SARS-CoV-2 FP. Furthermore, we generated K203.A, a new bsAb built in immunoglobulin G4-(single-chain variable fragment)2 forms and demonstrating a high manufacturing yield and nanomolar affinity to both the RBD and FP, by fusing K102.1, our previously reported RBD-specific mAb, with K107.1. ResultsOur comprehensive in vitro functional analyses revealed that the K203.A bsAb significantly outperformed the parental RBD-specific mAb in terms of neutralization efficacy against SARS-CoV-2 variants. Furthermore, intravenous monotherapy with K203.A demonstrated potent in vivo neutralizing activity without significant in vivo toxicity in a mouse model infected with a SARS-CoV-2 variant. ConclusionThese findings present a novel bsAb dual-targeting strategy, directed at SARS-CoV-2 RBD and FP, as an effective approach for rapid development and management against continuously evolving SARS-CoV-2 variants.

Background Sugammadex is a widely used medication for the reversal of aminosteroid neuromuscular blockades. Although sugammadex is generally regarded to be safe, concerns about the risk of serious complications have emerged. Case A 57-year-old man without a history of coronary disease was scheduled for general anesthesia to undergo cardiac radiofrequency catheter ablation due to symptomatic persistent atrial fibrillation and flutter. At the end of the procedure, he was given 400 mg of sugammadex. A little later, the electrocardiogram showed a sudden ST elevation on the inferior leads, followed by cardiac arrest. The urgent coronary angiography demonstrated total collapse of the right coronary artery. After two injections of intra-coronary nitroglycerin, the vasospasm of the right coronary artery was completely resolved. The patient recovered without sequelae and was discharged on postoperative day 5. Conclusions Clinicians should pay close attention to the potential risk of coronary vasospasm, even cardiac arrest, after sugammadex administration.

Abstract Here, we report a pathomimetic Leaky Gut Chip that recapitulates increased epithelial permeability and intestinal inflammation to assess probiotic intervention as live biotherapeutics. We leveraged a mechanodynamic human gut-on-a-chip (Gut Chip) that recreates three-dimensional epithelial layers in a controlled oxygen gradient and biomechanical cues, where the addition of a cocktail of pro-inflammatory cytokines, TNF-α and IL-1β, reproducibly induced impaired epithelial barrier followed by intestinal inflammation. This inflamed leaky epithelium was not recovered for up to 3 days, although the cytokine treatment ceased. However, when probiotic bacteria, either Lactobacillus rhamnosus GG or a multi-species mixture (VSL#3), were respectively administered on the leaky epithelium, bacterial cells colonized mucosal surface and significantly improved barrier function, enhanced the localization of tight junction proteins such as ZO-1 and occludin, and elevated mucus production. In addition, inflammatory markers, including p65, pSTAT3, and MYD88, that were highly expressed in the germ-free control were significantly reduced when probiotic bacteria were co-cultured in a Leaky Gut Chip. Probiotic treatment also significantly reduced the production of secretory pro-inflammatory cytokines. Hence, our pathomimetic Leaky Gut Chip may offer a translational strategy to dissect the therapeutic mechanism of live biotherapeutic products and validate their clinical potential by incorporating patient-derived organoids.

All-in-one treatments represent a paradigm shift in future medicine. For example, inflammatory bowel disease (IBD) is mainly diagnosed by endoscopy, which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels. Furthermore, molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy. This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component. These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy. Next, peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions, specifically by nanomicelles. The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation. Hence, the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5 (TLR5) as the main target of flagellin binding and Notch-1. The peptide binding potently suppressed inflammatory signaling without drug loading, where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha. The results were produced using a human colorectal cell line, clinical IBD patient cells, gut-on-a-chip, a mouse IBD model, and pig experiments to validate the translational utility.

Abstract We compared the risk of myocardial infarction (MI) or cerebral infarction (CI) in patients with or without-gallstone-related infection (GSI) and change in the risk following cholecystectomy. GSI (n = 84,467) and non-GSI (n = 406,800) patients with age- and sex-matched controls (n = 4,912,670) were identified from Korean population based data. The adjusted hazard ratios (aHRs) of MI or CI were analyzed in both groups treated with or without cholecystectomy. Subgroup analysis was performed for both sexes and different ages. The risk of MI or CI was higher in the GSI group than in the non-GSI group (aHR for MI; 1.32 vs. 1.07, aHR for CI; 1.24 vs. 1.06, respectively). The risk reduction rate of MI following cholecystectomy was 11.4% in the GSI group, whereas it was 0% in the non-GSI group. The risk of CI after cholecystectomy was more reduced in the GSI group than in the non-GSI group (16.1% and 4.7%, respectively). The original risk of MI or CI in patients with gallstones and risk reduction rates following cholecystectomy were higher in females and younger patients than in males and older patients. Increased risk of MI or CI and greater risk reduction following cholecystectomy were seen in patients with GSI.

The prevalence of emetic strains in food products is rare; however, infection with these may be fatal to the vulnerable population. Bacterial control of the emetic Bacillus cereus strains is still unclear. This study aimed to assess the influence of high temperature on the disinfection of emetic and enterotoxigenic B. cereus. Emetic B. cereus strains survived up to 50 °C; the lag time and maximum growth rate were higher at 42 °C than those at 30 °C. Compared to enterotoxigenic B. cereus, all emetic food strains showed higher minimum inhibitory concentrations and minimum bactericidal concentrations for sodium hypochlorite and citric acid. The disinfectant susceptibility of the emetic B. cereus OS-05 strain incubated at a higher temperature did not increase and was maintained at the highest MBC value. In all emetic B. cereus strains, enterotoxin gene expression was upregulated at 42 °C and 45 °C. Increased ces gene expression was also found in emetic B. cereus strains GP-15 and OS-05, with upregulation of 128- and 820-fold at 42 °C. Thus, emetic B. cereus grown at high temperatures may resist common disinfectants of the food industry. The findings may help control B. cereus in food or the food processing industry.

This study was undertaken to assess the potential of body mass index (BMI) as a risk factor for massive hemorrhage (MH) after cesarean section (CS) in patients with placenta previa. We retrospectively reviewed the medical records of patients who underwent CS for placenta previa between January 2010 and December 2018. MH was defined as an estimated blood loss ≥2,000 mL during surgery. Clinical characteristics, including BMI, were compared between the groups with and without MH. Subsequently, multivariable logistic regression analysis was conducted to identify the independent risk factors for MH. A total of 189 patients were included in this study. MH was observed in 28 patients (14.8%). According to the multivariable logistic regression analysis results, the risk factors independently associated with MH were BMI at delivery (adjusted odds ratio [aOR], 1.19; 95% confidence interval [CI], 1.04-1.35; P=0.012), placenta accreta (aOR, 24.55; 95% CI, 2.75-219.02; P=0.004), and total previa degree (aOR, 9.86; 95% CI, 2.71-35.96; P=0.001). The study findings showed that maternal obesity, namely a higher BMI at delivery, was an independent risk factor for MH after CS in patients with placenta previa. Close attention should be paid to the potential risk of hemorrhage associated with maternal obesity as well as the well-known risk factors of placenta accreta and total previa degree.

Here, we report a case of ultrasound-assisted subarachnoid block in a patient with severe kyphosis. A 69-year-old man was scheduled for metal removal from hip screws. He had a previous experience with subarachnoid block using the landmark-guided technique, but it was very difficult due to severe kyphosis. However, we could easily determine the correct needle insertion point using ultrasound imaging and performed a successful dural puncture on the first attempt. This case demonstrates the clinical usefulness of ultrasound imaging for subarachnoid blocks in patients with severe kyphosis.

Abstract Background There are no guidelines for straightforwardly managing advanced lung cancer (T3 or T4). Although surgery has traditionally been regarded as the mainstay treatment and the only curative modality, it has limited relevance for patients with locally advanced non-small cell lung cancer (NSCLC). Photodynamic therapy (PDT) is a clinically approved cancer therapy; it is an established treatment modality with curative intent for early-stage and superficial endobronchial lesions. However, the efficacy of PDT in advanced lung cancer is controversial, and it has primarily been used in palliative care. Case presentation This case report describes a 70-year-old male who had right upper lung cancer and an endobronchial lesion that extended into the distal trachea. A biopsy specimen was obtained upon bronchoscopy, and the result confirmed squamous cell carcinoma. We performed a definitive sleeve lobectomy and intraoperative PDT. Gross total resection of the tumor was achieved, but the presence of microscopic residual tumors was inevitable. Complete anatomical resection of the primary tumor by pneumonectomy was not possible due to poor lung function and endobronchial extension to the distal trachea. We decided to apply intraoperative PDT to the lumen and outer wall of the bronchi and distal trachea for local tumor control. The patient is alive with no evidence of disease after 13 months of follow-up. Conclusions This is the first report to describe the feasibility and efficacy of intraoperative PDT as part of multimodal therapy for locally advanced NSCLC.

Abstract Background Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. Methods A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled clinical trials (RCTs) of carbohydrate-restricted diets and ten articles on eight RCTs of IF was performed. Results Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Conclusion Here, we describe the results of our analysis and the evidence for these recommendations.

Long-term exposure to volatile organic compounds (VOCs) and carbonyl compounds in beauty products may adversely impact the health of beauty salon technicians. Previous studies have focused on assessing indoor air concentrations of chemicals, such as benzene and toluene, and not on personal exposure concentrations. This study measured the indoor and personal exposure concentrations of VOCs and carbonyl compounds in fifty-three beauty salons in Korea. Non-carcinogenic and carcinogenic risks and sensitivity were analyzed using the Monte Carlo simulation technique. The indoor and personal exposure concentrations of acetone were 82.24 µg/m3 and 104.97 µg/m3, respectively, the highest among all measured chemicals. Beauty salon technicians who experienced adverse health effects had significantly higher concentrations of acetone, benzaldehyde, and toluene than those who did not experience adverse health effects (p-value < 0.05). The average hazard quotients of formaldehyde and acetaldehyde were higher than the acceptable risk level (1), and the average cancer risks of formaldehyde exceeded the acceptable risk level (10−6). Wearing personal protective equipment was the most efficient risk reduction strategy for reducing the non-cancer risks of acetaldehyde and formaldehyde and the carcinogenic risks of formaldehyde. The results of this study can be used as a basis for reducing exposure to VOCs and carbonyl compounds among salon technicians.

Recent advances in asthma research have led to the development of novel biologicals that hinder the pathological actions of key molecules in severe asthma. Traditional randomised controlled studies (RCTs), the gold standard for evaluating the efficacy and safety of medical interventions with excellent internal validity, have proven the clinical benefits and favourable safety profiles of type 2 biologicals in severe asthma. However, RCTs are not always ideal because of shortcomings such as limited external validity and practical issues in the management of severe asthma that cannot be solved through strictly designed clinical trials. Thus, the applicability of their findings may be questioned because treatment adherence is frequently poor in the real world. Real-world evidence includes a wide range of real-world data (RWD) collected from multiple sources in clinical practice, such as electronic medical records, healthcare insurance claims and retrospective or prospective patient registries. RWD may help clinicians decide how to manage patients with severe asthma. Real-world evidence is also gaining attention in addressing clinical questions not answered by traditional RCTs. Because there are various types of RWD with different possibilities and limitations, it is important to decide which type of RWD could be “fit for purpose” to address a specific question. This narrative review discusses the challenges and opportunities of RWD for evaluating the effectiveness and clinical outcomes of biological treatments for severe asthma.

Abstract The habenula (Hb) is an epithalamic structure that links multiple forebrain areas with the mid/hindbrain monoaminergic systems. As an anti-reward center, it has been implicated in the etiology of various neuropsychiatric disorders, particularly those associated with dysregulated reward circuitry. In this regard, Hb has been proposed as a therapeutic target for treatment-resistant depression associated with a higher risk of suicide. Therefore, we aimed to gain insight into the molecular signatures of the Hb in association with suicide in individuals with major depression. Postmortem gene expression analysis identified 251 differentially expressed genes (DEGs) in the Hb tissue of suicides in comparison with Hb tissues from neurotypical individuals. Subsequent bioinformatic analyses using single-cell transcriptome data from the mouse Hb showed that the levels of a subset of endothelial cell-enriched genes encoding cell–cell junctional complex and plasma membrane-associated proteins, as well as the levels of their putative upstream transcriptional regulators, were significantly affected in suicides. Although our findings are based on a limited number of samples, the present study suggests a potential association of endothelial dysfunction in the Hb with depression and suicidal behavior.

Tissue clearing for 3-dimensional (3D) imaging is increasingly utilized in many biomedical applications, including the pathological examination of human biopsy specimens. Although many protocols offer rapid and efficient tissue clearing (>1 d), immunofluorescence labeling of thick specimens is a highly time-consuming process. The use of low molecular weight chemical dyes has potential benefits in terms of speed and quality of 3D labeling. Accordingly, we tested several chemical dyes to assess their potential applications in 3D imaging. The combination of SYTO 16 and eosin (S&E) was found to be a potential fluorescent version of the hematoxylin–eosin (H&E) stain. Furthermore, picrosirius red (for collagen), Congo red (for senile plaques), and fluorescent Nissl (for neurons in the normal brain or blood vessels in the injured brain) stains can be used alone or in combination with antibody labeling. As chemical labeling requires a relatively short incubation time (

Abstract Background The 6-min walk test (6MWT) and incremental shuttle walk test (ISWT) are valid and reliable measures to assess exercise capacity of patients with chronic obstructive pulmonary disease (COPD). However, the comparison of correlation between peak oxygen uptake (peak VO2) and 6MWT or ISWT distance has not been investigated. We aimed to investigate the correlation between peak VO2 and 6MWT and ISWT distances in COPD patients through a meta-analysis. Methods We systematically searched MEDLINE, Scopus, Embase, and the Cochrane Library up to June, 2020 for studies comparing the correlation of peak VO2 with either 6MWT or ISWT in COPD patients. Meta-analysis was performed with R software using a fixed-effect model. We compared the correlation coefficient and measured the heterogeneity using I2 statistics. Results We identified 12 studies involving 746 patients. Meta-analysis showed a significant correlation between peak VO2 and 6MWT and ISWT distances (6MWT: r = 0.65, 95% CI 0.61–0.70; ISWT: r = 0.81, 95% CI 0.74–0.85; p

Background and Objectives: Gramicidin, a bactericidal antibiotic used in dermatology and ophthalmology, has recently garnered attention for its inhibitory actions against cancer cell growth. However, the effects of gramicidin on ovarian cancer cells and the underlying mechanisms are still poorly understood. We aimed to elucidate the anticancer efficacy of gramicidin against ovarian cancer cells. Materials and Methods: The anticancer effect of gramicidin was investigated through an in vitro experiment. We analyzed cell proliferation, DNA fragmentation, cell cycle arrest and apoptosis in ovarian cancer cells using WST-1 assay, terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL), DNA agarose gel electrophoresis, flow cytometry and western blot. Results: Gramicidin treatment induces dose- and time-dependent decreases in OVCAR8, SKOV3, and A2780 ovarian cancer cell proliferation. TUNEL assay and DNA agarose gel electrophoresis showed that gramicidin caused DNA fragmentation in ovarian cancer cells. Flow cytometry demonstrated that gramicidin induced cell cycle arrest. Furthermore, we confirmed via Western blot that gramicidin triggered apoptosis in ovarian cancer cells. Conclusions: Our results strongly suggest that gramicidin exerts its inhibitory effect on cancer cell growth by triggering apoptosis. Conclusively, this study provides new insights into the previously unexplored anticancer properties of gramicidin against ovarian cancer cells.

Background & aimsChronic rhinosinusitis (CRS) is one of the most prevalent upper respiratory tract diseases. However, little is known the effect of CRS on the cardiovascular aspects of patients. This study aimed to investigate the incidence of acute myocardial infarction (AMI) in patients with CRS compared with that in the general population.MethodsThis retrospective cohort study was performed using the Korean National Health Insurance Service (NHIS) database. To minimize confounding, age, sex, and cardiovascular risk profiles were adjusted. The primary endpoint was newly diagnosed AMI in patients between January 2005 and December 2018. The relative risk of AMI in patients with CRS was compared with that in controls. Kaplan-Meier survival curves and Cox proportional regression tests were used for statistical analyses.ResultsAmong 5,179,981 patients from the NHIS database, 996,679 patients with CRS were selected. The control group was 10 times (n = 9,966,790) the number of individuals in the CRS group. The CRS group had better cardiovascular profiles than those of the control group and had an adjusted hazard ratio of 0.99 (95% confidence interval, 0.97-1.02) for AMI.ConclusionThere was no significant association between the two groups regardless of the presence of nasal polyps. This is the first study adjusting cardiovascular risk profiles and analyzing the relationship between CRS and AMI. CRS was not associated with a high incidence of AMI after adjusting for cardiovascular risk factors.

Summary: The human gut-on-a-chip has demonstrated in vivo-relevant cellular fidelity and physiological functions of Caco-2 intestinal epithelium compared to its static cultures. However, transcriptomic dynamics that controls the morphogenic and mechanodynamic perturbation of Caco-2 epithelium in a microphysiological culture remain elusive. Single-cell transcriptomic analysis revealed that a gut-on-a-chip culture drives three clusters that illustrate distinct gene expressions and their spatial representation in three-dimensional (3D) epithelial layers. A pseudotemporal trajectory analysis elucidated the evolutionary transition from a homogeneous ancestral genotype in Transwell cultures into heterogeneous transcriptomes in gut-on-a-chip cultures, verified in cell cycle perturbation, cytodifferentiation, and intestinal functions in digestion, transport, and drug metabolism. Furthermore, the inversed transcriptomic signature of oncogenes and tumor-suppressor genes of Caco-2 cells confirmed that gut-on-a-chip cultures induce post-mitotic reprogramming of cancer-associated genes. Our study suggests that a physiological gut-on-a-chip culture induces the transcriptomic perturbation of Caco-2 epithelium to elicit in vivo-relevant morphogenesis and restoration of normal physiological functions.

Abstract Although surgery is the gold standard for treatment of primary spontaneous pneumothorax (PSP), recurrence after surgery remains a concern. This study sought to evaluate the efficacy of simultaneous pleurodesis using Viscum album (VA) extract and video-assisted thoracic surgery (VATS) bullectomy for the treatment of PSP. From March 2016 to June 2020, 175 patients with PSP underwent bullectomy and intraoperative pleurodesis with VA extract at a single institution. All operations were performed through thoracoscopy by one surgeon. Upon completion of bullectomy, a polyglycolic acid sheet was used to cover the stapler lines, and 40 mg of VA extract was instilled over the entire chest wall before chest tube placement. The median operating time was 20 min (interquartile ranges, 15–30) and the median indwelling time of chest drainage was 2 days (interquartile ranges, 2–3). There were no postoperative complications over grade 3. During the median follow-up period of 38 months (interquartile ranges, 15–48), no recurrence of pneumothorax was observed. The results of this study demonstrated that simultaneous Viscum pleurodesis and VATS bullectomy provides a feasible and effective treatment option for preventing postoperative pneumothorax in patients with PSP.

Abstract Background Photoactivation targeting macrophages has emerged as a therapeutic strategy for atherosclerosis, but limited targetable ability of photosensitizers to the lesions hinders its applications. Moreover, the molecular mechanistic insight to its phototherapeutic effects on atheroma is still lacking. Herein, we developed a macrophage targetable near-infrared fluorescence (NIRF) emitting phototheranostic agent by conjugating dextran sulfate (DS) to chlorin e6 (Ce6) and estimated its phototherapeutic feasibility in murine atheroma. Also, the phototherapeutic mechanisms of DS-Ce6 on atherosclerosis were investigated. Results The phototheranostic agent DS-Ce6 efficiently internalized into the activated macrophages and foam cells via scavenger receptor-A (SR-A) mediated endocytosis. Customized serial optical imaging-guided photoactivation of DS-Ce6 by light illumination reduced both atheroma burden and inflammation in murine models. Immuno-fluorescence and -histochemical analyses revealed that the photoactivation of DS-Ce6 produced a prominent increase in macrophage-associated apoptotic bodies 1 week after laser irradiation and induced autophagy with Mer tyrosine-protein kinase expression as early as day 1, indicative of an enhanced efferocytosis in atheroma. Conclusion Imaging-guided DS-Ce6 photoactivation was able to in vivo detect inflammatory activity in atheroma as well as to simultaneously reduce both plaque burden and inflammation by harmonic contribution of apoptosis, autophagy, and lesional efferocytosis. These results suggest that macrophage targetable phototheranostic nanoagents will be a promising theranostic strategy for high-risk atheroma. Graphical abstract