Development of chimeric antigen receptor (CAR)-T cells targeting A56 viral protein implanted by oncolytic virus.

To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.

CRIF1 deficiency induces FOXP3LOW inflammatory non-suppressive regulatory T cells, thereby promoting antitumor immunity.

Recently identified human FOXP3lowCD45RA- inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (Tregs). In spite of their implication in tumors, the mechanism for generation of FOXP3lowCD45RA- INS cells in vivo is unclear. We showed that the FOXP3lowCD45RA- cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3lowINS-Tregs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinflammatory cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased α-ketoglutarate-derived 2-hydroxyglutarate down-regulated Foxp3 expression by methylating the Foxp3 gene regulatory regions. Furthermore, CRIF1 deficiency-induced Foxp3lowINS-Tregs suppressed tumor growth in an IFN-γ-dependent manner. Thus, CRIF1 deficiency-mediated mitochondrial dysfunction results in the induction of Foxp3lowINS-Tregs including FOXP3lowCD45RA- cells that promote antitumor immunity.

Peptide-Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis-Like Inflammation.

Peptide-drug conjugates (PDCs) are a promising class of drug delivery systems that utilize covalently conjugated carrier peptides with therapeutic agents. PDCs offer several advantages over traditional drug delivery systems including enhanced target engagement, improved bioavailability, and increased cell permeability. However, the development of efficient transcellular peptides capable of effectively transporting drugs across biological barriers remains an unmet need. In this study, physicochemical criteria based on cell-penetrating peptides are employed to design transcellular peptides derived from an antimicrobial peptides library. Among the statistically designed transcellular peptides (SDTs), SDT7 exhibits higher skin permeability, faster kinetics, and improved cell permeability in human keratinocyte cells compared to the control peptide. Subsequently, it is found that 6-Paradol (PAR) exhibits inhibitory activity against phosphodiesterase 4, which can be utilized for an anti-inflammatory PDC. The transcellular PDC (SDT7-conjugated with PAR, named TM5) is evaluated in mouse models of psoriasis, exhibiting superior therapeutic efficacy compared to PAR alone. These findings highlight the potential of transcellular PDCs (TDCs) as a promising approach for the treatment of inflammatory skin disorders.

Research status of east Asian traditional medicine treatment for chronic cough: A scoping review.

BACKGROUND: When patients continue to experience cough despite conventional treatment, East Asian traditional medicine (EATM) including herbal medicine and/or acupuncture has been frequently used. Previous systematic reviews of EATM treatment for chronic cough have been conducted mainly on herbal medicine, targeting patients with conditions that cause cough. In clinical practice, EATM interventions are not limited to herbal medicine, and considering that chronic cough is often caused by two or more conditions or unspecific causes, a comprehensive investigation is clinically relevant. We examined the current research status of EATM for chronic cough. METHODS: Based on Arksey and O'Malley's scoping review methodological framework, a total of six English, Chinese, Korean, and Japanese electronic databases were searched on August 2022. Any clinical studies on EATM targeting chronic cough patients (regardless of their cause) were included. RESULTS: Among 474 included studies, the study designs were mainly randomized controlled trials (72.4%), and the population was evenly distributed between children and adults. The cause of cough was not reported in most studies (56.1%). The common cause of cough was upper airway cough syndrome and post-respiratory infection (9.5%, each), followed by mixed cause (7.6%), nonspecific cause (5.9%), and gastroesophageal reflux disease (4.0%). EATM was conducted for a mean of 19.1 days, and herbal medicine was the most common (80.6%). Conventional medication was frequently used as a control (81.2%). For outcomes, the total effective rate was the most frequently utilized (94.3%), followed by cough severity (53.8%). EATM treatment showed positive outcomes in most studies. CONCLUSIONS: In future EATM studies, it is necessary to either specify the cause of chronic cough or to report that the study was targeting nonspecific chronic cough. In addition, high-quality studies assessing the efficacy of EATM with placebo control treatment should be conducted, using validated evaluation tools.

Macrophage activation syndrome in neonatal lupus presenting with fever and rash.

Neonatal lupus can occur in infants born to mother with autoimmune disorders through transplacental auto-antibodies. Clinical manifestations in neonatal lupus include cutaneous lesions and hematologic or hepatobiliary findings resembling those seen in systemic lupus erythematosus. In autoimmune state, macrophage activation syndrome (MAS) represent a critical and potentially fatal complication that can result in mortality if not immediately identified and managed with the appropriate care. Here we present a 33-day-old girl diagnosed with neonatal lupus and serious MAS. She was delivered by a primipara mother who did not exhibit any autoimmune symptoms. The patient visited the hospital due to fever and pancytopenia. Laboratory data were compatible with MAS, including pancytopenia, high level of ferritin, soluble interleukin-2, and decreased natural killer cell activity. In addition, autoimmune study showed positive results for anti-nuclear antibody (ANA), anti-Sjogren syndrome antigen A (SSA), and SSB, The autoimmune study for mother also showed positive results for ANA, anti-SSA, and SSB. The patient recovered after she received high dose steroid and supportive care. Our case indicates that neonatal lupus should be taken into consideration when fever, erythematous skin rash, and pancytopenia are observed in infants, even if their mothers have no prior history of autoimmune conditions.

Comparison of specificity and sensitivity of diagnostic methods for Enteromyxum leei and Enteromyxum fugu detected from cultured tiger puffer, Takifugu rubripes in Korea.

Enteromyxum leei and Enteromyxum fugu, which are myxosporean parasites, were first found in cultured tiger puffer Takifugu rubripes in Korea. We collected four tiger puffers that showed severe emaciation signs for our experiments. DNA sequencing was confirmed that the tiger puffers were coinfected with E. leei and E. fugu. Furthermore, similar amounts of E. leei and E. fugu were confirmed using real-time PCR in the intestine. To the best of our knowledge, there have been no reports of E. fugu infection in the olive flounder Paralichthys olivaceus. However, the diagnosis of inflowing water, discharged water and olive flounder samples using highly sensitive diagnostic methods confirmed the presence of E. fugu in water and fish samples from olive flounder farms near the tiger puffer farm. Therefore, the present study aimed to develop highly sensitive diagnostic methods such as real-time and two-step PCR for early diagnosis and follow-up of the emaciation disease and multiplex PCR for rapid diagnosis. The multiplex PCR method exhibited the same sensitivity as the one-step PCR method developed in this study, demonstrating its efficacy for rapid diagnosis. Therefore, the suggested methods can be utilized for the early diagnosis and rapid diagnosis of emaciation diseases and reduction of economic losses through rapid disease control.

Mechanistic insights into the anti-restenotic effects of HSP27 and HO1 modulated by reconstituted HDL on neointimal hyperplasia.

High-density lipoprotein (HDL) therapy has demonstrated beneficial effects in acute stroke and acute myocardial infarction models by reducing infarct size. In this study, we investigated the inhibitory effects of reconstituted HDL (rHDL) on neointimal hyperplasia and elucidated its underlying mechanism using a balloon injury rat model. Our finding revealed a significant 37% reduction in the intima to media ratio in the arteries treated with 80 mg/kg rHDL compared to those subjected to injury alone (p < 0.05), indicating a specific inhibition of neointimal hyperplasia. In vivo analysis further supported the positive effects of rHDL by demonstrating a reduction in smooth muscle cell (SMC) proliferation and an increase in endothelial cell (EC) proliferation. Additionally, rHDL treatment led to decreased infiltration of leukocytes and downregulated the expression of matrix metallopeptidase 9 (MMP9) in the neointimal area. Notably, rHDL administration resulted in decreased expression of VCAM1 and HIF1α, alongside increased expression of heme oxygenase 1 (HO1) and heat shock protein 27 (HSP27). Overexpression of HSP27 and HO1 effectively inhibited SMC proliferation. Moreover, rHDL-mediated suppression of injury-induced HIF1α coincided with upregulation of HSP27. Interestingly, HSP27 and HO1 had varying effects on the expression of chemokine receptors and rHDL did not exert significant effect on chemokine receptor expression in THP1 cells. These findings underscore the distinct roles of HSP27 and HO1 as potential regulatory factors in the progression of restenosis. Collectively, our study demonstrates that rHDL exerts a potent anti-neointimal hyperplasia effect by reducing leukocytes infiltration and SMC proliferation while promoting EC proliferation.

Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis.

Objectives: Chronic cough is a frequent condition worldwide that significantly impairs quality of life. Herbal medicine (HM) has been used to treat chronic cough due to the limited effectiveness of conventional medications. This study aimed to summarize and determine the effects of HM on patients with chronic cough. Methods: A comprehensive search of 11 databases was conducted to find randomized controlled clinical trials (RCTs) that reported the effects of HM for patients with chronic cough on 16 March 2023. The primary outcome was cough severity, and the secondary outcomes included cough-related quality of life, cough frequency, total effective rate (TER), and cough recurrence rate. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and the certainty of the evidence for effect estimates was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations tool. Results: A total of 80 RCTs comprising 7,573 patients were included. When HM was used as an alternative therapy to conventional medication, there were inconsistent results in improving cough severity. However, HM significantly improved cough-related quality of life and TER and significantly lowered the cough recurrence rate compared with conventional medication. When used as an add-on therapy to conventional medication, HM significantly improved cough severity, cough-related quality of life, and TER and significantly lowered the recurrence rate. In addition, HM had a significantly lower incidence of adverse events when used as an add-on or alternative therapy to conventional medication. The subgroup analysis according to age and cause of cough also showed a statistically consistent correlation with the overall results. The certainty of the evidence for the effect of HM was generally moderate to low due to the risk of bias in the included studies. Conclusion: HM may improve cough severity and cough-related quality of life, and lower the cough recurrence rate and incidence of adverse events in patients with chronic cough. However, due to the high risk of bias and clinical heterogeneity of the included studies, further high-quality placebo-controlled clinical trials should be conducted using a validated and objective assessment tool. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418736, CRD42023418736.

Using an Online Panel to Crosswalk Alternative Measures of Alcohol Use As Fielded in Two National Samples.

Introduction: Accurate estimation of the health effects of drinking is hampered by inconsistent phrasing of questions about alcohol use in commonly-used health surveys (e.g., HRS, NYLS79), and measurement error in brief self-reports of drinking. We fielded an online survey to a diverse pool of respondents, assessing two versions of alcohol use questions. We used the measurement survey responses to evaluate correspondence across question versions and create a crosswalk between versions of alcohol questions from two different nationally representative studies of middle-aged adults. The measurement model can also be used to incorporate measurement error correction. Methods: Respondents to two measurement survey platforms (Centiment and Qualtrics) were asked drinking frequency and quantity questions as phrased in the Health and Retirement Study (HRS: average days per week drank in the last 3 months; quantity consumed on days drank in the last 3 months) and differently phrased questions from the National Longitudinal Survey of Youth 1979 (NLSY79: days drank in last 30 days, average quantity consumed on days drank). The order in which respondents encountered different versions of the questions was randomized. From these questions, we derived measures of average weekly alcohol consumption. In the online panel data, we regressed responses to the HRS question on responses to the NLSY question and vice versa to create imputation models. HRS (n=14,639) and NLSY79 (n=7,069) participants aged 50-59 self-rated their overall health (range 0-4, 0=excellent and 4=poor). NLSY79 or HRS participants' responses to the alcohol question from the other survey were multiply imputed (k=30) using the measurement model from the measurement survey participant data (k=30). We regressed self-rated health on each alcohol measure and estimated covariate-adjusted coefficients from observed and imputed versions of the questions. Results: The measurement survey (n=2,070) included respondents aged 50+; 64.8% female; 21.4% Hispanic, 23.95% Black, 27.1% White, and 27.6% another ("Other") self-reported racial/ethnic identity. Associations of observed alcohol question responses with self-reported health were slightly smaller than associations of imputed responses for frequency of alcohol use and consumption on days when alcohol was used. For example, using the HRS version of the frequency of alcohol use (days per week), the estimate for the observed question in HRS respondents was ꞵ =-0.045 [-0.055,-0.036]; and the estimate for the imputed version of the HRS question in NLSY79 respondents was ꞵ=-0.051 [-0.065,-0.037]. The estimated effect of average drinks per week was substantially larger for the imputed version of the measure (ꞵ for the observed question in HRS=-0.002 [-0.004,0.001], ꞵ for the imputed version of the HRS measure in NLSY79 respondents=-0.02 [-0.027,-0.012]). Patterns were similar when using the NLSY79 versions of questions as reported in NLSY79 and imputed for HRS respondents. For example, the estimated effect of average drinks per week was substantially larger for the imputed version of the NLSY79 question (ꞵ for the observed question in NLSY79=-0.006 [-0.01,-0.002], ꞵ for the imputed version of the HRS question in NLSY79 respondents=-0.019 [-0.027,-0.01]). Conclusions: Measurement inconsistencies and imperfect reliability are major challenges in estimating effects of alcohol use on health. Collecting additional data using online panels is a feasible and flexible approach to quantifying measurement differences. This approach may enable measurement error corrections, improve meta-analyses, and promote evidence triangulation.

Efficient and sustainable water electrolysis achieved by excess electron reservoir enabling charge replenishment to catalysts.

Suppressing the oxidation of active-Ir(III) in IrOx catalysts is highly desirable to realize an efficient and durable oxygen evolution reaction in water electrolysis. Although charge replenishment from supports can be effective in preventing the oxidation of IrOx catalysts, most supports have inherently limited charge transfer capability. Here, we demonstrate that an excess electron reservoir, which is a charged oxygen species, incorporated in antimony-doped tin oxide supports can effectively control the Ir oxidation states by boosting the charge donations to IrOx catalysts. Both computational and experimental analyses reveal that the promoted charge transfer driven by excess electron reservoir is the key parameter for stabilizing the active-Ir(III) in IrOx catalysts. When used in a polymer electrolyte membrane water electrolyzer, Ir catalyst on excess electron reservoir incorporated support exhibited 75 times higher mass activity than commercial nanoparticle-based catalysts and outstanding long-term stability for 250 h with a marginal degradation under a water-splitting current of 1 A cm-2. Moreover, Ir-specific power (74.8 kW g-1) indicates its remarkable potential for realizing gigawatt-scale H2 production for the first time.

A booster administration of the OKA/SK strain causes fatal disseminated varicella in an immunocompetent child.

Live varicella vaccines are known to provide robust immunity against varicella zoster virus (VZV) infections. However, problems with viral attenuation have led to pathogenic VZV vaccine strains causing varicella-like rash and herpes zoster in immunocompetent children after immunization. We report the first fatal case of VZV infection caused by OKA/SK strain contained in the vaccine administrated as a booster shot in an immunocompetent child, which has been independently developed from any currently available varicella vaccines that are OKA strain or MAV/06 strain based. The patient died due to sudden pulmonary alveolar hemorrhage as a secondary complication of VZV pneumonitis. Sequencing of the four SNPs unique to the OKA/SK strain (SNP loci 14 035T; 32 626C; 58 777G; 70 319G) enabled discrimination of the strain responsible for the disseminated infection. OKA/SK strain does not have any SNPs in ORF62 postulated to be responsible for the attenuation of varicella vaccines which have been safely and effectively used world-wide or locally, and exclusively enriches a virulent factor in ORF31 identified in parental OKA strain, thus possibly resulting in disseminated VZV infection leading to mortality. Therefore, actions need to be taken to prevent vaccine related morbidity and mortality in children.

Sensor development for multiple simultaneous classifications using genetically engineered M13 bacteriophages.

Sensors for detecting infinitesimal amounts of chemicals in air have been widely developed because they can identify the origin of chemicals. These sensing technologies are also used to determine the variety and freshness of fresh food and detect explosives, hazardous chemicals, environmental hormones, and diseases using exhaled gases. However, there is still a need to rapidly develop portable and highly sensitive sensors that respond to complex environments. Here, we show an efficient method for optimising an M13 bacteriophage-based multi-array colourimetric sensor for multiple simultaneous classifications. Apples, which are difficult to classify due to many varieties in distribution, were selected for classifying targets. M13 was adopted to fabricate a multi-array colourimetric sensor using the self-templating process since a chemical property of major coat protein p8 consisting of the M13 body can be manipulated by genetic engineering to respond to various target substances. The twenty sensor units, which consisted of different types of manipulated M13, exhibited colour changes because of the change of photonic crystal-like nanostructure when they were exposed to target substances associated with apples. The classification success rate of the optimal sensor combinations was achieved with high accuracy for the apple variety (100%), four standard fragrances (100%), and aging (84.5%) simultaneously. We expect that this optimisation technique can be used for rapid sensor development capable of multiple simultaneous classifications in various fields, such as medical diagnosis, hazardous environment monitoring, and the food industry, where sensors need to be developed in response to complex environments consisting of various targets.

Comparison of associations of household-level and neighbourhood-level poverty markers with paediatric asthma care utilisation by race/ethnicity in an open cohort of community health centre patients.

OBJECTIVE: The objective of this research was to examine how different measurements of poverty (household-level and neighborhood-level) were associated with asthma care utilisation outcomes in a community health centre setting among Latino, non-Latino black and non-Latino white children. DESIGN, SETTING AND PARTICIPANTS: We used 2012-2017 electronic health record data of an open cohort of children aged <18 years with asthma from the OCHIN, Inc. network. Independent variables included household-level and neighborhood-level poverty using income as a percent of federal poverty level (FPL). Covariate-adjusted generalised estimating equations logistic and negative binomial regression were used to model three outcomes: (1) ≥2 asthma visits/year, (2) albuterol prescription orders and (3) prescription of inhaled corticosteroids over the total study period. RESULTS: The full sample (n=30 196) was 46% Latino, 26% non-Latino black, 31% aged 6-10 years at first clinic visit. Most patients had household FPL <100% (78%), yet more than half lived in a neighbourhood with >200% FPL (55%). Overall, neighbourhood poverty (<100% FPL) was associated with more asthma visits (covariate-adjusted OR 1.26, 95% CI 1.12 to 1.41), and living in a low-income neighbourhood (≥100% to <200% FPL) was associated with more albuterol prescriptions (covariate-adjusted rate ratio 1.07, 95% CI 1.02 to 1.13). When stratified by race/ethnicity, we saw differences in both directions in associations of household/neighbourhood income and care outcomes between groups. CONCLUSIONS: This study enhances understanding of measurements of race/ethnicity differences in asthma care utilisation by income, revealing different associations of living in low-income neighbourhoods and households for Latino, non-Latino white and non-Latino black children with asthma. This implies that markers of family and community poverty may both need to be considered when evaluating the association between economic status and healthcare utilisation. Tools to measure both kinds of poverty (family and community) may already exist within clinics, and can both be used to better tailor asthma care and reduce disparities in primary care safety net settings.

Using adenosine triphosphate bioluminescence level monitoring to identify bacterial reservoirs during two consecutive Enterococcus faecium and Staphylococcus capitis nosocomial infection outbreaks at a neonatal intensive care unit.

INTRODUCTION: This study aimed to assess the role of adenosine triphosphate (ATP) bioluminescence level monitoring for identifying reservoirs of the outbreak pathogen during two consecutive outbreaks caused by Enterococcus faecium and Staphylococcus capitis at a neonatal intensive care unit (NICU). The secondary aim was to evaluate the long-term sustainability of the infection control measures employed one year after the final intervention measures. METHODS: Two outbreaks occurred during a 53-day period in two disconnected subunits, A and B, that share the same attending physicians. ATP bioluminescence level monitoring, environmental cultures, and hand cultures from healthcare workers (HCW) in the NICU were performed. Pulsed-field gel electrophoresis (PFGE) typing was carried out to investigate the phylogenetic relatedness of the isolated strains. RESULTS: Four cases of E. faecium sepsis (patients A-8, A-7, A-9, B-8) and three cases of S. capitis sepsis (patients A-16, A-2, B-8) were diagnosed in six preterm infants over a span of 53 days. ATP levels remained high on keyboard 1 of the main station (2076 relative light unit [RLU]/100 cm2) and the keyboard of bed A-9 (4886 RLU/100 cm2). By guidance with the ATP results, environmental cultures showed that E. faecium isolated from the patients and from the main station's keyboard 1 were genotypically indistinguishable. Two different S. capitis strains caused sepsis in three patients. A total 77.8% (n = 7/9) of S. capitis cultured from HCW's hands were genotypically indistinguishable to the strains isolated from A-2 and A-16. The remaining 22.2% (n = 2/9) were genotypically indistinguishable to patient B-8. Three interventions to decrease the risk of bacterial transmission were applied, with the final intervention including a switch of all keyboards and mice in NICU-A and B to disinfectable ones. Post-intervention prospective monitoring up to one year showed a decrease in blood culture positivity (P = 0.0019) and catheter-related blood stream infection rate (P = 0.016) before and after intervention. CONCLUSION: ATP monitoring is an effective tool in identifying difficult to disinfect areas in NICUs. Non-medical devices may serve as reservoirs of pathogens causing nosocomial outbreaks, and HCWs' hands contribute to bacterial transmission in NICUs.

CTHRC1 Induces Pancreatic Stellate Cells (PSCs) into Myofibroblast-like Cancer-Associated Fibroblasts (myCAFs).

[BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1-PSCs-cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation.

Photothermally Active Core-Shell Catalyst Based on UiO-66 and Polydopamine for Highly Effective Detoxification of Nerve Agents.

A new, photothermally active, catalytic composite (Fe3O4@PD@UiO-66) based on UiO-66 and polydopamine (PD) was prepared for the decomposition of chemical warfare agents (CWAs). An iron oxide nanoparticle was introduced to enable rapid recovery after the reaction. The PD layer enabled conversion of the absorbed light into heat under infrared (IR) irradiation and increased the reaction temperature, thereby increasing the reaction rate. Dendrimer-functionalized silica particles (NH2-DS) were used as heterogeneous catalyst regenerators instead of N-ethylmorpholine. Under IR irradiation, a mixture of Fe3O4@PD@UiO-66 and NH2-DS was effective as a heterogeneous catalyst for degrading DMNP, with a 5 min half-life in water. Without IR irradiation, the half-life of DMNP was 45 min using the same catalyst mixture. Various bases including arginine, histidine, and D4 were directly modified on the surface of Fe3O4@PD@UiO-66 and used without NH2-DS or N-ethylmorpholine in order to compare their reactivities. Furthermore, a mixture of Fe3O4@PD@UiO-66 and NH2-DS was used for the decomposition of nerve agents, including sarin (GB), soman (GD), and VX, under IR-LED irradiation. Remarkably, GB was effectively decomposed with a half-life of 4.2 min, and GD demonstrated a half-life of 8.7 min. VX was hydrolyzed with a half-life of 14.0 min.

The transcription factor Mef2d regulates B:T synapse-dependent GC-TFH differentiation and IL-21-mediated humoral immunity.

Communication between CD4 T cells and cognate B cells is key for the former to fully mature into germinal center-T follicular helper (GC-TFH) cells and for the latter to mount a CD4 T cell-dependent humoral immune response. Although this interaction occurs in a B:T synapse-dependent manner, how CD4 T cells transcriptionally regulate B:T synapse formation remains largely unknown. Here, we report that Mef2d, an isoform of the myocyte enhancer factor 2 (Mef2) transcription factor family, is a critical regulator of this process. In CD4 T cells, Mef2d negatively regulates expression of Sh2d1a, which encodes SLAM-associated protein (SAP), a critical regulator of B:T synapses. We found that Mef2d regulates Sh2d1a expression via DNA binding-dependent transcriptional repression, inhibiting SAP-dependent B:T synapse formation and preventing antigen-specific CD4 T cells from differentiating into GC-TFH cells. Mef2d also impeded IL-21 production by CD4 T cells, an important B cell help signaling molecule, via direct repression of the Il21 gene. In contrast, CD4 T cell-specific disruption of Mef2d led to a substantial increase in GC-TFH differentiation in response to protein immunization, concurrent with enhanced SAP expression. MEF2D mRNA expression inversely correlates with human systemic lupus erythematosus (SLE) patient autoimmune parameters, including circulating TFH-like cell frequencies, autoantibodies, and SLEDAI scores. These findings highlight Mef2d as a pivotal rheostat in CD4 T cells for controlling GC formation and antibody production by B cells.

Cost-effectiveness analysis of herbal medicines in children with idiopathic short stature.

BACKGROUND: Herbal medicines have been used for a long time to treat idiopathic short stature (ISS) in children in East Asian countries. The aim of this study was to analyze the cost-effectiveness of 5 herbal medicines frequently used in clinical settings for children with ISS based on medical records. METHODS: Patients with ISS who had been prescribed a 60-day supply of herbal medicines in 1 Korean medicine hospital were included in this analysis. Their height and height percentile were measured before and after treatment within 6-months. The average cost-effectiveness ratios (ACERs) of 5 herbal medicines for height (cm) and height percentile were calculated for boys and girls, respectively. RESULTS: The ACERs per 1 cm height growth were USD 56.2 (Naesohwajung-Tang), USD 74.8 (Ogapi-Growth decoction), USD 86.6 (Gamcho-Growth decoction), USD 94.6 (Gwakhyangjeonggi-San plus Yukmijihwang-Tang), and USD 113.8 (Boyang-Growth decoction). The ACERs per 1 percentile height growth were USD 205 (Naesohwajung-Tang), USD 293 (Ogapi-Growth decoction), USD 470 (Gamcho-Growth decoction), USD 949 (Boyang-Growth decoction), and USD 1051 (Gwakhyangjeonggi-San plus Yukmijihwang-Tang). CONCLUSION: Herbal medicine might be a potential economical alternative treatment for ISS.

4-EA-NBOMe, an amphetamine derivative, alters glutamatergic synaptic transmission through 5-HT1A receptors on cortical neurons from SpragueDawley rat and pyramidal neurons from C57BL/6 mouse.

New psychoactive substances (NPSs) are compounds designed to mimic illegal recreational drugs. In particular, there are difficulties in legal restrictions because there is no fast NPS detection method to suppress the initial spread of NPS with criminal records; thus, they expose the public to serious health threats, including toxicity and dependence. However, the effects of NPSs on the brain and the related cellular mechanisms are well unknown. One of the recently emerging drugs is 4-ethylamphetamine-NBOMe (4-EA-NBOMe), a member of the 2 C phenylalanine family with a similar structure to methamphetamine (methA). In this study, we tested the effect of methA analogs on the glutamatergic synaptic transmission on primary cultured cortical neurons of SpragueDawley (SD) rats and C57BL/6 mice, and also layer 2/3 pyramidal neurons of the medial prefrontal cortex (mPFC) of C57BL/6 mice. We found that acute treatment with 4-EA-NBOMe inhibits spontaneous excitatory postsynaptic currents (EPSCs) and that withdrawal after chronic inhibition by 4-EA-NBOMe augments glutamatergic synaptic transmission. These modifications of synaptic responses are mediated by 5-HT1A receptors. These findings suggest that 4-EA-NBOMe directly affects the central nervous system by changing the efficacy of glutamatergic synaptic transmission.