Therapeutic potential of ginseng leaf extract in inhibiting mast cell-mediated allergic inflammation and atopic dermatitis-like skin inflammation in DNCB-treated mice.

Ginseng leaves are known to contain high concentrations of bioactive compounds, such as ginsenosides, and have potential as a treatment for various conditions, including fungal infections, cancer, obesity, oxidative stress, and age-related diseases. This study assessed the impact of ginseng leaf extract (GLE) on mast cell-mediated allergic inflammation and atopic dermatitis (AD) in DNCB-treated mice. GLE reduced skin thickness and lymph node nodules and suppressed the expression and secretion of histamine and pro-inflammatory cytokines. It also significantly lowered the production of inflammatory response mediators including ROS, leukotriene C4 (LTC4), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). GLE inhibited the phosphorylation of MAPKs (ERK, P38, JNK) and the activation of NF-κB, which are both linked to inflammatory cytokine expression. We demonstrated that GLE's inhibitory effect on mast cell-mediated allergic inflammation is due to the blockade of the NF-κB and inflammasome pathways. Our findings suggest that GLE can be an effective therapeutic agent for mast-cell mediated and allergic inflammatory conditions.

Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants that Confer Risk for Breast Cancer.

Breast cancer includes several subtypes with distinct characteristic biological, pathological, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate development of improved prevention and treatment approaches. Here, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case GWAS (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead variants in 12 loci remained statistically significant after accounting for previously reported breast cancer susceptibility variants, among which two were genome-wide significant. Fine mapping implicated putative functional/causal variants and risk genes at several loci, e.g., 3q26.31/TNFSF10, 8q22.3/NACAP1/GRHL2, and 8q23.3/LINC00536/TRPS1, for TNBC as compared to luminal cancer. Functional investigation further identified rs16867605 at 8q22.3 as a SNP that modulates enhancer activity of GRHL2. Subtype-informative polygenic risk scores (PRS) were derived, and patients with a high subtype-informative PRS had an up to 2-fold increased risk of being diagnosed with TNBC instead of luminal cancers. The CC-GWAS PRS remained statistically significant after adjusting for TNBC PRS derived from traditional case-control GWAS in The Cancer Genome Atlas and the African Ancestry Breast Cancer Genetic Consortium. The CC-GWAS PRS was also associated with overall survival and disease-specific survival among breast cancer patients. Overall, these findings have advanced our understanding of the genetic etiology of breast cancer subtypes, particularly for TNBC.

Multifunctional MXene/Carbon Nanotube Janus Film for Electromagnetic Shielding and Infrared Shielding/Detection in Harsh Environments.

Multifunctional, flexible, and robust thin films capable of operating in demanding harsh temperature environments are crucial for various cutting-edge applications. This study presents a multifunctional Janus film integrating highly-crystalline Ti3C2Tx MXene and mechanically-robust carbon nanotube (CNT) film through strong hydrogen bonding. The hybrid film not only exhibits high electrical conductivity (4250 S cm-1), but also demonstrates robust mechanical strength and durability in both extremely low and high temperature environments, showing exceptional resistance to thermal shock. This hybrid Janus film of 15 µm thickness reveals remarkable multifunctionality, including efficient electromagnetic shielding effectiveness of 72 dB in X band frequency range, excellent infrared (IR) shielding capability with an average emissivity of 0.09 (a minimal value of 0.02), superior thermal camouflage performance over a wide temperature range (- 1 to 300 °C) achieving a notable reduction in the radiated temperature by 243 °C against a background temperature of 300 °C, and outstanding IR detection capability characterized by a 44% increase in resistance when exposed to 250 W IR radiation. This multifunctional MXene/CNT Janus film offers a feasible solution for electromagnetic shielding and IR shielding/detection under challenging conditions.

Alamouti-coded DSP algorithm with a simplified PTBC decoder for next-generation optical access networks.

The use of Alamouti-coded polarization-time block code (A-PTBC) in combination with a simple single polarization coherent receiver enables phase-diverse coherent detection without any optical polarization tracking. However, applying this technique to high-speed single-carrier systems is not straightforward, as it requires specialized digital signal processing (DSP) algorithms for data recovery, which increases DSP complexity. In this paper, we propose a novel Alamouti-coded coherent algorithm designed to significantly reduce the complexity of the receiver DSP for data recovery. The proposed algorithm achieves the comparable performance to the conventional algorithm but requires only half the number of necessary equalizers for data recovery. We validate its performance through simulations and also experimentally demonstrate a 100 Gb/s 16-quadrature amplitude modulation (QAM) single-carrier coherent system employed the single-polarization coherent receiver over 20 km of standard single-mode fiber (SMF). Through the performance verification, the coherent system with the proposed algorithm exhibits performance comparable to that of the conventional Alamouti-coded coherent system and achieves a power budget of 34 dB when the transmit launch power is set to 7 dBm at a Bit Error Rate (BER) of 1 × 10-2 for 0-20 km fiber transmission.

Fabrication of thermo-responsive multicore microcapsules using a facile extrusion process.

A process employing extrusion was used to produce multicore microcapsules composed of multiple beads. The inner beads were made from κ-carrageenan (κ-c), a thermo-responsive linear sulphated polymer whose gelling temperature ranges at 40-60 °C, depending on the concentration of κ-c polymer and the amount of potassium chloride used for gelation. The resulting beads were then enveloped by chitosan through gelation with sodium triphosphate. The pesticide ammonium glufosinate was encapsulated in the κ-c/chitosan multicore microcapsules for demonstration of controlled release of the encapsulant. It was found that in response to an external stimulus, such as elevated temperature or solar simulation, the microcapsules exhibit the gradual release of encapsulated pesticide molecules from multicore microcapsules, compared with beads only. This process of making multicore microcapsules can be extended to other polymer pairs based on applications. This work is relevant to agriculture, where the controlled-release of the pesticides or fertilizers could be triggered by the sun and/or temperature changes, thus extending the residual period of the chemicals as well as decreasing the extent of pollution by leaching of abundant chemicals.

Bismuth-Based Quadruple Therapy as First-Line Treatment for Clarithromycin-resistant Helicobacter pylori Infection: A Prospective Randomized Comparison of 7- and 14-Day Treatment Regimens.

Background/Aims: : Bismuth-based quadruple therapy (BQT) is a treatment option for clarithromycin-resistant Helicobacter pylori (HP) infection. The aim of this study was to compare the efficacy of 7-day BQT with that of 14-day BQT as first-line treatment for clarithromycin-resistant HP infection. Methods: : A total of 162 treatment-naïve patients with peptic ulcer disease and clarithromycin-resistant HP infection confirmed by real-time polymerase chain reaction (RT-PCR) were enrolled. The enrolled patients were prospectively randomized to receive BQT for either 7 or 14 days of treatment. Eradication of HP infection was assessed using a 13C-urea breath test. Eradication and adverse event rates of the two groups were assessed. Results: : The overall eradication rates in the intention-to-treat (ITT) and per-protocol (PP) analyses were 83.0% (95% confidence interval [CI], 77.2% to 88.9%; 132/159) and 89.8% (95% CI, 84.9% to 94.7%; 132/147), respectively. The eradication rates in the ITT analysis were 79.0% (64/81) in the 7-day group and 87.2% (68/78) in the 14-day group (p=0.170). The eradication rates in the PP analysis were 86.5% (64/74) in the 7-day group and 93.2% (68/73) in the 14-day group (p=0.182). Clinically significant adverse events occurred in 18.2% of patients. There was no statistically significant difference in the rates of individual or all adverse events between the two groups. Conclusions: : Both 7-day and 14-day BQT were effective and safe as first-line therapy for HP infections identified as resistant to clarithromycin by RT-PCR. For clarithromycin-resistant HP infections, 7-day BQT may be sufficient as first-line therapy.

Characteristics and Trends of Pediatric Trauma in Jeju Island, South Korea: A Community Level Serial Cross-sectional study.

Objective: This study aimed to investigate the characteristics and epidemiological trends of pediatric injuries among patients visiting emergency departments (EDs) on Jeju Island. Method: Employing a community-level serial cross-sectional analysis, we targeted pediatric patients aged 18 years or younger who visited EDs for injuries over a ten-year period. The data, sourced from the Jeju Injury Surveillance System (JISS), facilitated a comprehensive examination of injury characteristics and epidemiological trends. This included an evaluation of the annual incidence and overall trends in pediatric injury cases. Results: The study found toddlers (42.5% of cases) to be the most frequently injured age group. Males were more prone to injuries, with a male-to-female ratio of 1.7:1. Injuries among visitors accounted for 17.3% of cases, with a seasonal spike in Summer, evenings and weekends. Most incidents occurred at home, predominantly accidental in nature, with adolescents more likely to require EMS services. The common mechanisms of injuries were blunt force (49.2%), slips/falls (22.0%), and motor vehicle collisions (13.2%), leading to bruises, cuts, and sprains. Over the decade, a general increase in pediatric injuries was observed. Accidental injuries initially surged but later stabilized, while self-harm/suicide and assault/violence injuries showed a concerning upward trend. Age-specific analysis revealed increasing trends in infants and adolescents. Conclusion: The study underscores the crucial need for targeted injury prevention and resource allocation strategies, particularly for high-risk groups and times, to effectively mitigate pediatric trauma on Jeju Island.

Enhanced electrophysiological activity and neurotoxicity screening of environmental chemicals using 3D neurons from human neural precursor cells purified with PSA-NCAM.

The assessment of neurotoxicity for environmental chemicals is of utmost importance in ensuring public health and environmental safety. Multielectrode array (MEA) technology has emerged as a powerful tool for assessing disturbances in the electrophysiological activity. Although human embryonic stem cell (hESC)-derived neurons have been used in MEA for neurotoxicity screening, obtaining a substantial and sufficiently active population of neurons from hESCs remains challenging. In this study, we successfully differentiated neurons from a large population of human neuronal precursor cells (hNPC) purified using a polysialylated neural cell adhesion molecule (PSA-NCAM), referred to as hNPCPSA-NCAM+. The functional characterization demonstrated that hNPCPSA-NCAM+-derived neurons improve functionality by enhancing electrophysiological activity compared to total hNPC-derived neurons. Furthermore, three-dimensional (3D) neurons derived from hNPCPSA-NCAM+ exhibited reduced maturation time and enhanced electrophysiological activity on MEA. We employed subdivided population analysis of active mean firing rate (MFR) based on electrophysiological intensity to characterize the electrophysiological properties of hNPCPSA-NCAM+-3D neurons. Based on electrophysiological activity including MFR and burst parameters, we evaluated the sensitivity of hNPCPSA-NCAM+-3D neurons on MEA to screen both inhibitory and excitatory neuroactive environmental chemicals. Intriguingly, electrophysiologically active hNPCPSA-NCAM+-3D neurons demonstrated good sensitivity to evaluate neuroactive chemicals, particularly in discriminating excitatory chemicals. Our findings highlight the effectiveness of MEA approaches using hNPCPSA-NCAM+-3D neurons in the assessment of neurotoxicity associated with environmental chemicals. Furthermore, we emphasize the importance of selecting appropriate signal intensity thresholds to enhance neurotoxicity prediction and screening of environmental chemicals.

Target trial emulation of carfilzomib safety among patients with relapsed/refractory multiple myeloma using a nationwide observational data in Korea.

PURPOSE: Carfilzomib, commonly used for relapsed/refractory multiple myeloma (RRMM), has been associated with various adverse events in randomized controlled trials (RCTs). However, real-world safety data for a more diverse population are needed, as carfilzomib received expedited approval. This study aimed to evaluate carfilzomib's safety in Korea by comparing new users of KRd (carfilzomib, lenalidomide, and dexamethasone) to Rd (lenalidomide and dexamethasone) using a nationwide administrative claims database. METHODS: The retrospective cohort study utilized target trial emulation, focusing on adverse events in various organ systems similar to the ASPIRE trial. RESULTS: This study included 4,580 RRMM patients between 2007 and 2020, and the KRd group showed significantly higher risks of hematologic adverse events (anemia, neutropenia, thrombocytopenia) and some non-hematologic adverse events (cough, hypokalemia, constipation, hypertension, heart failure) compared to the Rd group. Among non-hematologic adverse events, cardiovascular events (heart failure [HR 2.04; 95% CI 1.24-3.35], hypertension [HR 1.58; 95% CI 1.15-2.17]) had the highest risk in the KRd group. CONCLUSION: The safety profile of carfilzomib in Korean patients was similar to previous RCTs. Therefore, caution should be exercised when using carfilzomib in Asian individuals with RRMM due to the increased risk of cardiovascular adverse events.

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: exploring the influence of prior transarterial chemoembolization and additional transarterial chemoembolization on survival outcomes.

Background: The selection of an efficacious treatment modality for patients with hepatocellular carcinoma (HCC) diagnosed as refractory to transarterial chemoembolization (TACE) presents numerous challenges. In addition to systemic therapies, hepatic arterial infusion chemotherapy (HAIC) may serve as an alternative option. However, it is imperative to identify patients who are appropriate candidates for HAIC to confer a survival benefit. Our study aimed to evaluate the impact of the number of TACE sessions prior to HAIC treatment and the addition of TACE during HAIC on the survival of HCC patient's refractory to TACE. Methods: This retrospective study included 82 patients with HCC refractory to TACE (mean age 60.5 years, 75 males). Survival analysis was conducted using the Kaplan-Meier method, with comparison between two groups via the log-rank test; the Cox regression model was utilized to identify factors influencing survival. Results: The overall response rate (ORR) was observed to be 29.3%, with a disease control rate (DCR) of 56.1%. Patients receiving more than four TACE sessions prior to HAIC exhibited a significantly poorer survival prognosis compared to those receiving fewer than four TACE sessions, with a hazard ratio (HR) of 0.151 (P=0.02). The median overall survival (OS) was markedly different, being 3.4 (range, 0.5-13.6) months for the former group and 14 (range, 8.5-19.5) months for the latter (P=0.01). Furthermore, patients undergoing additional TACE while receiving HAIC treatment demonstrated improved survival outcomes compared to those who did not, with an HR of 0.491 (P=0.02); the respective OS for these groups was 14 (range, 3.6-14.4) and 6.7 (range, 2.8-11) months (P=0.02). Conclusions: HAIC can be a suitable alternative treatment for HCC patient's refractory to TACE. For those with a history of more than 4 TACE sessions, other alternative treatments should be considered. The addition of TACE during HAIC treatment may extend patient OS time, provided it is balanced with maintaining safe liver function.

Abnormal Silicon Etching Behaviors in Nanometer-Sized Channels.

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

Higher objective responses by hepatic arterial infusion chemotherapy following atezolizumab and bevacizumab failure than when used as initial therapy in hepatocellular carcinoma: a retrospective study.

PURPOSE: Atezolizumab/bevacizumab (atezo-bev) is the first-line chemotherapy for patients with unresectable hepatocellular carcinoma (HCC). However, hepatic artery infusion chemotherapy (HAIC) can be used as an alternative. Our aim was to compare the prognosis of HAIC treatment between newly diagnosed patients and patients treated after failure of atezo-bev. METHODS: We retrospectively assessed 73 patients with HCC treated with HAIC between January 2022 and September 2023. Fifty-seven patients were treated with HAIC at initial diagnosis, while 16 were treated with HAIC after first-line atezo-bev combination chemotherapy. We evaluated tumor responses, such as overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: No significant difference was observed in either OS or PFS between patients with HCC treated with HAIC at the initial diagnosis and those treated after atezo-bev treatment failure. However, the ORR of the initial HAIC group was 19.6% and that of the HAIC group after atezo-bev therapy failure was 43.6%, which was a statistically significantly difference. CONCLUSION: Although no significant difference was observed for OS and PFS, the ORR of patients in the HAIC group after the failure of atezo-bev therapy was superior to that of newly diagnosed patients. HAIC may prolong survival in patients with HCC after atezo-bev treatment failure.

Complete and Incomplete Alcohol Sclerotherapy for Treatment of Symptomatic Hepatic Cysts: Comparison of Volume Reduction and Clinical Outcomes.

Background: The purpose of this study was to compare the efficacy of incomplete alcohol sclerotherapy with complete treatment for hepatic cysts. Methods: From 2005 to 2021, a total of 80 patients (19 males, 61 females; median age 65 years; age range, 42-86 years) who underwent alcohol sclerotherapy for symptomatic benign hepatic cysts were enrolled and retrospectively reviewed. Complete treatment was defined as injecting 25-33% of the aspirated cyst volume with alcohol in 2-3 cycles, with a maximum of 100 mL per cycle. The overall volume reduction rate was compared between the complete and incomplete treatment groups. The response, based on cystic volume reduction, was classified as a complete regression (CR), near-complete regression (NCR), partial regression (PR), or no response (NR). CR and NCR were considered objective responses. Among 80 patients with 85 hepatic cysts, 26 patients with 29 hepatic cysts received incomplete treatment. Results: The overall volume reduction rate was not significantly different between the complete and incomplete treatment groups (94.39% vs. 95.47%, respectively, p = 0.623). The CR and NCR groups showed a significantly higher rate of symptom improvement than the PR and NR groups (p = 0.043). Conclusions: In conclusion, the efficacy of incomplete alcohol sclerotherapy was not inferior to that of complete treatment.

Incidence and Risk Factors of Acute Ischemic Cholecystitis after Transarterial Chemoembolization: Correlation with Cone Beam CT Findings.

Purpose: Acute cholecystitis is a complication of transarterial chemoembolization (TACE) that occasionally requires surgical intervention. We aimed to analyze the incidence and risk factors of cholecystitis requiring surgical intervention in patients with embolic material uptake on cone beam CT (CBCT) performed immediately after various TACE procedures. Materials and Methods: After a retrospective review of 2633 TACE procedures performed over a 6-year period, 120 patients with embolic material retention in the gallbladder wall on CBCT immediately after TACE were selected. We analyzed the incidence of and risk factors for acute cholecystitis. Results: The overall incidence of acute cholecystitis requiring surgical intervention was 0.45% (12 of 2633 TACE procedures); however, it was present in 10% (12 of 120) of procedures that showed high-density embolic material retention in the gallbladder wall on CBCT performed immediately after TACE. Acute cholecystitis requiring surgical intervention occurred in eight patients (66.7%) who underwent direct cystic arterial embolization. Surgical intervention was performed 15 days (mean) after TACE. Conclusion: Most unintended chemolipiodol deposits in the gallbladder wall resolved without intervention or surgery. However, superselective direct cystic arterial chemoembolization was associated with a high incidence of acute cholecystitis requiring surgery, and patients who undergo this procedure should be closely monitored.

Mercury monitoring in the coastal areas of the Republic of Korea using the black-tailed gull egg as an indicator.

In the southeast and east coasts of the Republic of Korea, it is essential to monitor mercury accumulation in coastal organisms in view of the higher mercury distribution in sediments and human samples. However, mercury pollution monitoring in organisms, especially higher trophic-level organisms that can exhibit high mercury accumulation, is limited. Here, we examined the applicability of the eggs of the black-tailed gull (Larus crassirostris), which belongs to a high trophic level, for mercury monitoring in coastal areas. Breeding sites were selected in West, Southeast, and East Seas with different mercury concentrations in other matrices (sediment and biological samples of residents). The 5-year mean total mercury concentration in eggs collected during the breeding seasons from 2016 to 2020 was lower in Baengnyeongdo (705 ± 81 ng/g dry weight (dry), West Sea) than in Hongdo (1,207 ± 214 ng/g dry, Southeast Sea) and Ulleungdo (1,095 ± 95 ng/g dry, East Sea). The different patterns of mercury concentration in gull eggs among the breeding sites was consistent with those in the other matrices among the coastal areas. These results support the applicability of the black-tailed gull egg as an indicator for establishing a monitoring framework in the coastal areas of the Republic of Korea.

Role of Portosystemic Shunt and Portal Vein Stent in Managing Portal Hypertension Due to Hematological Diseases.

INTRODUCTION: Patients with hematological diseases experience complications related to portal hypertension, including life-threatening complications such as variceal bleeding. METHODS: We analyzed the prognosis of patients with hematological diseases and portal hypertension treated with transjugular intrahepatic portosystemic shunts (TIPS) or portal vein stents. We retrospectively assessed patients with hematological diseases and portal hypertension who had variceal bleeding. We evaluated the characteristics and prognosis of the enrolled patients. A total of 11 patients with hematological diseases who underwent TIPS, or portal vein stenting, were evaluated. RESULTS: The median follow-up period was 420 days. Of the 11 patients, eight showed resolution of portal hypertension and its complications following TIPS, or stent insertion. One patient experienced rebleeding due to incomplete resolution of portal hypertension, and two other patients also experienced rebleeding because they underwent TIPS closure or revision due to repetitive hepatic encephalopathy. CONCLUSION: Portosystemic shunt and stent installation are effective treatment options for portal hypertension due to hematological diseases.

Safety assessment and gastrointestinal retention of orally administered cerium oxide nanoparticles in rats.

Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the "no observed adverse effect level" of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.

Fibrates and risk of congenital malformations: a nationwide cohort study in South Korea.

PURPOSE: To examine the association between maternal prescriptions for fibrates and congenital malformations in live births. METHODS: Nationwide retrospective cohort study was conducted using the data sourced from the Korean National Health Insurance database. A cohort of 756,877 completed pregnancies linked to live-born infants in 215,600 women with dyslipidemia between 2012 and 2021. The study compared data on congenital anomalies between pregnancies who were exposed to fibrates and those who were not exposed to fibrates in the first trimester. Odds ratios (OR) were calculated by a multivariable analyses using logistic regression models to adjust for potential confounders. RESULTS: 260 pregnancies (0.12%) were exposed to fibrates during the first trimester. The prevalence of malformations in exposed offspirng was 10.77%, not significantly different compared with 9.68% in offspring of women who were not prescribed fibrates during pregnancy in patients with dyslipidemia (OR 1.13; 95% CI 0.75-1.70). CONCLUSION: This study implies that the use of fibrates during pregnancy may be safe, as it did not show any association with congenital anomalies. However, caution is warranted due to an elevated risk associated with prolonged exposure.

Design, Synthesis, and Acid-Responsive Disassembly of Shell-Sheddable Block Copolymer Labeled with Benzaldehyde Acetal Junction.

Smart nanoassemblies degradable through the cleavage of acid-labile linkages have attracted significant attention because of their biological relevance found in tumor tissues. Despite their high potential to achieve controlled/enhanced drug release, a systematic understanding of structural factors that affect their pH sensitivity remains challenging, particulary in the consruction of effective acid-degradable shell-sheddable nanoassemblies. Herein, the authors report the synthesis and acid-responsive degradation through acid-catalyzed hydrolysis of three acetal and ketal diols and identify benzaldehyde acetal (BzAA) exhibiting optimal hydrolysis profiles in targeted pH ranges to be a suitable candidate for junction acid-labile linkage. The authors explore the synthesis and aqueous micellization of well-defined poly(ethylene glycol)-based block copolymer bearing BzAA linkage covalently attached to a polymethacrylate block for the formation of colloidally-stable nanoassemblies with BzAA groups at core/corona interfaces. Promisingly, the investigation on acid-catalyzed hydrolysis and disassembly shows that the formed nanoassemblies meet the criteria for acid-degradable shell-sheddable nanoassemblies: slow degradation at tumoral pH = 6.5 and rapid disassembly at endo/lysosomal pH = 5.0, while colloidal stability at physiological pH = 7.4. This work guides the design principle of acid-degradable shell-sheddable nanoassemblies bearing BzAA at interfaces, thus offering the promise to address the PEG dilemma and improve endocytosis in tumor-targeting drug delivery.