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An acute brain lesion (ABL) identified by brain magnetic resonance imaging (MRI) after acute carbon monoxide (CO) poisoning is a strong prognostic factor for the development of delayed neuropsychiatric syndrome (DNS). This study aimed to identify predictors of ABLs on MRI in patients with acute CO poisoning. This was a multicenter prospective registry-based observational study conducted at two tertiary hospitals. A total of 1,034 patients were included. Multivariable logistic regression analysis showed that loss of consciousness (LOC) (adjusted odds ratio [aOR] 2.68, 95% Confidence Interval [CI]: 1.49-5.06), Glasgow Coma Scale (GCS) score < 9 (aOR 2.41, 95% CI: 1.49-3.91), troponin-I (TnI) (aOR 1.22, 95% CI: 1.08-1.41), CO exposure duration (aOR 1.09, 95% CI: 1.05-1.13), and white blood cell (WBC) (aOR 1.05, 95% CI: 1.01-1.09) were independent predictors of ABLs on MRI. LOC, GCS score, TnI, CO exposure duration, and WBC count can be useful predictors of ABLs on MRI in patients with acute CO poisoning, helping clinicians decide the need for an MRI scan or transfer the patient to an appropriate institution for MRI or hyperbaric oxygen therapy., (© 2023. The Author(s).)

Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the "don't-eat-me" signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML., (© 2023 by The American Society of Hematology.)

The study aimed to investigate the antioxidant and antidiabetic activity of Brugmansia arborea L. flower extracts, solvent fractions, and isolated compounds. B. arborea L flowers were extracted with aqueous methanol, and concentrated extract was successively partitioned into EtOAc, n -BuOH, and H 2 O fractions. Repeated silica gel and octadecyl silica gel column chromatographies for EtOAc and n -BuOH fractions led to the isolation of a new phenylalkyl glycoside ( 6 ), along with five known ones. Several spectroscopic data led to the structure determination of one new phenylalky glycoside as brugmansioside C (named) ( 6 ) and five known ones as benzyl- O - β -D-glucopyranoside ( 1 ), benzyl- O - β -D-glucosyl-(1→6)- β -D-glucopyranoside ( 2 ), 2-phenylethyl- O - β -D-glucopyranoside ( 3 ), 2-phenylethyl- O - β -D-glucosyl-(1→6)- β -D-glucopyranoside ( 4 ), and 3-phenylpropyl- O - β -D-glucopyranoside ( 5 ). The five known ones ( 1 - 5 ) were isolated from B. arborea flowers for the first time in this study. The extract, solvent fractions, and all isolated compounds showed radical scavenging activities using ABTS radical, and EtOAc fraction showed the highest scavenging capacity, whereas compounds 2, 4, and 6 did not display the capacity to use the DPPH radical. The extract, solvent fractions, and all isolated compounds showed a protective effect on pancreatic islets damaged by alloxan treatment in zebrafish larvae. The pancreatic islet size treated with EtOAc, n -BuOH fractions, and all compounds significantly increased by 64.0%, 69.4%, 82.0%, 89.8%, 80.0%, 97.8%, 103.1%, and 99.6%, respectively, compared to the alloxan-induced group. These results indicate that B. arborea flowers and their isolated compounds are useful as potential antioxidant and antidiabetic agents.

ATP-binding cassette (ABC) transporters, notably ABCB1 (P-glycoprotein) and ABCG2, play a crucial role in the development of multidrug resistance (MDR) during the administration of chemotherapy for cancer patients. With a lack of approved treatments for addressing multidrug-resistant cancers, MDR remains a substantial challenge to the effective management of cancer. Rather than focusing on developing novel synthetic inhibitors, a promising approach to combat MDR involves repurposing approved therapeutic agents to enhance the sensitivity to cytotoxic antiproliferative drugs of multidrug-resistant cancer cells with high expression of ABCB1 or ABCG2. In this investigation, we observed a substantial reversal of MDR conferred by ABCB1 and ABCG2 in multidrug-resistant cancer cells through the use of mobocertinib, an approved third-generation inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. Mobocertinib demonstrated the ability to hinder drug transport function without causing changes in protein expression. The interactions between mobocertinib and ABCB1, as well as ABCG2, were validated through ATPase assays. Furthermore, in silico docking simulations were utilized to substantiate the binding of mobocertinib within the drug-binding pockets of both ABCB1 and ABCG2. We conclude that further testing of mobocertinib in combination therapy is warranted for patients with tumors expressing elevated levels of the ABC drug transporters ABCB1 and ABCG2., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as novel cardioprotective agents. However, their direct impact on cardiomyocyte injury is yet to be studied. In this work, we investigate the underlying molecular mechanisms of empagliflozin (EMPA), an SGLT2 inhibitor, in mitigating palmitate (PA)-induced cardiomyocyte injury in H9c2 cells. We found that EMPA significantly attenuated PA-induced impairments in insulin sensitivity, ER stress, inflammatory cytokine gene expression, and cellular apoptosis. Additionally, EMPA elevated AMP levels, activated the AMPK pathway, and increased carnitine palmitoyl transferase1 (CPT1) gene expression, which collectively enhanced fatty acid oxidation and reduced stress signals. This study reveals a novel mechanism of EMPA's protective effects against PA-induced cardiomyocyte injury, providing new therapeutic insights into EMPA as a cardioprotective agent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Cui, Lee, Cui, Son, Kim, Kim, Kim, Choi, Kang, Kim, Jeon and Lee.)

Background: Previous studies suggest that aromatase inhibitors (AIs) increase the risk of adverse cardiovascular events and cardiac arrhythmias in patients with breast cancer, but it is unclear whether AIs also increase the risk of new-onset atrial fibrillation (AF)., Objectives: The purpose of this study was to investigate whether the use of AIs was associated with an increased risk of new-onset AF in patients with breast cancer., Methods: We performed a retrospective analysis involving 5,707 patients with breast cancer (mean age 63.9 ± 11.2 years and 99.9% women) who received adjunctive hormone therapy with an AI (AI group, n = 4,878) or tamoxifen (tamoxifen group, n = 829) in Hong Kong between January 1, 1999, and December 31, 2020. After propensity score matching, there were 1,658 and 829 patients with balanced characteristics in the AI group and tamoxifen group, respectively., Results: After 8,863 patient-years of follow-up, patients who were prescribed AI had a trend toward more new-onset arrhythmias compared with those prescribed tamoxifen (0.62 vs 0.30 per 100 patient-years; crude HR: 2.05; P = 0.053). The difference in arrhythmic risk was mainly driven by a higher incidence rate of new-onset AF in the AI group (0.59 vs 0.27 per 100 patient-years; crude HR: 2.18; P = 0.046). The use of AIs was confirmed to be an independent risk factor for new-onset AF on multivariate analysis (adjusted HR: 2.75; P = 0.01)., Conclusions: Among breast cancer patients prescribed adjunctive hormonal therapy, AI was associated with an increased risk of new-onset AF. Regular surveillance for new-onset AF should be considered in breast cancer patients treated with an AI., Competing Interests: This study was partly supported by the Li Shu Pui Medical Foundation Fellowship/Dean’s Fund, Li Shu Pui Medical Foundation, and the University of Hong Kong; and by the Li Shu Fan Medical Fellowship for Internal Medicine, Li Shu Fan Medical Foundation, and the University of Hong Kong, Hong Kong SAR. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

A bulk-heterojunction (BHJ) blend is commonly used as the photoactive layer in organic photodetectors (OPDs) to utilize the donor (D)/acceptor (A) interfacial energetic offset for exciton dissociation. However, this strategy often complicates optimization procedures, raising serious concerns over device processability, reproducibility, and stability. Herein, highly efficient OPDs fabricated with single-component organic semiconductors are demonstrated via solution-processing. The non-fullerene acceptors (NFAs) with strong intrinsic D/A character are used as the photoactive layer, where the emissive intermolecular charge transfer excitonic (CTE) states are formed within <1 ps, and efficient photocurrent generation is achieved via strong quenching of these CTE states by reverse bias. Y6 and IT-4F-based OPDs show excellent OPD performances, low dark current density (≈10 -9 A cm -2 ), high responsivity (≥0.15 A W -1 ), high specific detectivity (>10 12 Jones), and fast photo-response time (<10 µs), comparable to the state-of-the-art BHJ OPDs. Together with strong CTE state quenching by electric field, these excellent OPD performances are also attributed to the high quadrupole moments of NFA molecules, which can lead to large interfacial energetic offset for efficient CTE dissociation. This work opens a new way to realize efficient OPDs using single-component systems via solution-processing and provides important molecular design rules., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Breast cancer is one of the major malignancies in women, and most related deaths are due to recurrence, drug resistance, and metastasis. The expression of the mouse double minute 2 (MDM2) oncogene is upregulated in breast cancer; however, its regulatory mechanism has yet to be fully elucidated. Herein, we identified the tumor suppressor death-associated protein kinase 1 (DAPK1) as a novel MDM2 regulator by unbiased peptide library screening. DAPK1 is directly bound to MDM2 and phosphorylates it at Thr419. DAPK1-mediated MDM2 phosphorylation promoted its protein degradation via the ubiquitin-proteasome pathway, resulting in upregulated p53 expression. DAPK1 overexpression, but not its kinase activity-deficient form, decreased colony formation and increased doxorubicin-induced cell death; however, DAPK1 knockdown produced the opposite effects in human breast cancer cells. In a xenograft tumorigenesis assay, DAPK1 overexpression significantly reduced tumor formation, whereas inhibition of DAPK1 kinase activity reduced its antitumorigenic effect. Finally, DAPK1 expression was negatively correlated with MDM2 levels in human breast cancer tissues. Thus, these results suggest that DAPK1-mediated MDM2 phosphorylation and its protein degradation may contribute to its antitumorigenic function in breast cancer., (© 2023. The Pharmaceutical Society of Korea.)

Background: Postpancreatectomy hemorrhage (PPH) is the most feared complication after pancreaticoduodenectomy (PD). The most common cause is erosion of the gastroduodenal artery stump. Preventive measures have been previously reported, but a consensus is lacking. The aim of this study was to analyze the preventive effect of reinforcing the hepatic artery using a polyglycolic acid (PGA) sheet during PD., Methods: A multicenter retrospective study was performed, collecting data from three tertiary hospitals in Korea. Patients receiving PD from January 2016 to December 2021 were included. The primary endpoint was rate of PPH from the hepatic artery. Arterial reinforcement (AR) was performed by wrapping the artery with Neoveil (Gunze Ltd) and applying fibrin glue. The perioperative data of patients who did not receive AR were compared with data of those who received AR., Results: A total of 904 patients were analyzed. The rate of PPH from the hepatic artery was significantly lower in the AR group. (3.5% vs 0.7%, p = .002) In patients with CR-POPF, the 90 day mortality rate of the AR group was less than half that of the non-AR group (7.2% vs 3.5%, p = .455) Risk factor analysis showed CR-POPF to be an independent risk factor for PPH. Arterial reinforcement was shown to be a strong protective factor for PPH (OR 0.20, 95% CI: 0.05-0.72, p = .014)., Conclusions: AR of the hepatic artery using Neoveil and fibrin glue is a simple method that greatly reduces the rate of PPH after PD., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: This study aimed to investigate the diagnostic performance of the rapid antigen test (RAT) for screening patients with cycle threshold (Ct) values of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) in the emergency department. Previous studies have shown that Ct values could be used as indicators of infectiousness. Therefore, we considered the Ct value an indicator of potential infectiousness., Methods: This single-center retrospective observational study was conducted between January 1, 2020, and March 31, 2022. Patients who underwent both RT-PCR and RAT for the diagnosis of COVID-19 were included. Patients with negative RT-PCR results were excluded. Patients with Ct values lower than 26 and 30 were considered potentially infectious for COVID-19., Result: A total of 386 patients were analyzed. At Ct value cutoffs of 26 and 30, the result of the RAT showed a sensitivity of 82% and 74%, specificity of 84% and 89%, and area under the curve (AUC) of 0.829 and 0.813, respectively, in the receiver operating characteristic curve. However, the NPV was relatively low at 55% and 25%., Conclusion: The RAT might be a rapid screening tool for detecting patients with the infectiousness of SARS-CoV-2. However, considering the low NPV, it is challenging to depend only on a negative test result from an antigen test to terminate quarantine. Clinicians should consider additional factors, such as the duration of symptoms and the immunocompromised state, for SARS-CoV-2 transmission., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Rachycentron canadum (cobia) is a marine fish species of high economic value in aquaculture due to its fast growth rate and good feed conversion efficacy. Regrettably, the industry has been affected by significant setbacks from high mortality due to diseases. Consequently, an improved perception of innate immunity correlated to each mucosal-associated lymphoid tissue (MALT) in teleost fish is necessary to understand hosts' response towards infections better. The utilization of polysaccharides in seaweed to stimulate the immune system has gathered unprecedented attention. The present study examined the immunostimulatory effects of Sarcodia suae water extracts (SSWE) on in vivo gill-, gut- and skin-associated lymphoid tissues (GIALT, GALT, and SALT) via immersion and oral ingestions. The GIALT genes (TNF-α, Cox2, IL-1β, IL-6, IL-8, IL-17 A/F1-3, IL-11, IL-12, IL-15, IL-18, MHCIa, IgM, and IgT) except IL-10 recorded positive upregulations in a dose-dependent manner post 24 h immersion in SSWE, indicating the algae extract contained bioactive compounds that could stimulate the immune genes. The upregulation of IL-12, IL-15, and IL-18 in the gills and hindgut post-SSWE immersion indicated that the extract could promote Th1-related responses in the MALTs. The modulation of immune gene expressions in the feeding trial was less potent than in the SSWE immersion. These findings indicated that the SSWE stimulated robust immune responses in both the GIALT and GALT of cobia. This suggests that the SSWE could be further explored as an effective immersive stimulant for fish, enhancing their immune system against pathogens., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Development of highly efficient and robust electrocatalysts for oxygen evolution reaction (OER) under specific electrolyte is a key to actualize commercial low-temperature water electrolyzers. Herein, a rational catalyst design strategy is first reported based on amorphous-crystalline (a-c) interfacial engineering to achieve high catalytic activity and durability under diverse electrolytes that can be used for all types of low-temperature water electrolysis. Abundant a-c interface (ACI) is implemented into a hollow nanocubic (pre)-electrocatalyst which is derived from Ir-doped Ni-Fe-Zn Prussian blue analogues (PBA). The implemented c-a interface is well maintained during prolonged OER in alkaline, alkalized saline, and acidic electrolytes demonstrating its diverse functionality for water electrolysis. Notably, the final catalyst exhibits superior catalytic activity with excellent durability for OER compared to that of benchmark IrO 2 catalyst, regardless of chemical environment of electrolytes. Hence, this work can be an instructive guidance for developing the ACI engineered electroctalyst which can be diversely used for different types of low-temperature electrolyzers., (© 2023 Wiley-VCH GmbH.)

In chronic hepatitis B (CHB) patients, quantification of HBV pgRNA in plasma has the potential to provide information on disease prognosis and liver injury or histopathology. However, current methods for detecting HBV pgRNA present technical difficulties due to the co-existence of HBV DNA in plasma samples. We have successfully established a novel one-step RT-PCR assay that allows selective quantification of HBV pgRNA. Two cohorts of participants were recruited for assay validation, including treatment-naïve patients with CHB and HBeAg-positive CHB patients who were treated with Tenofovir and monitored for 6 months to assess the predictive value of baseline HBV RNA for HBeAg seroclearance. Statistical analysis was performed using MedCalc version 20.019 software. The novel selective one-step RT-PCR assay for detecting HBV pgRNA was validated with a limit of detection of 100 copies/mL. The assay was able to selectively measure HBV pgRNA even in the presence of excess HBV rcDNA. In treatment-naïve CHB patients, HBV pgRNA levels were significantly lower than HBV DNA concentration. Serum HBV DNA levels and HBeAg status were positively associated with HBV pgRNA. Baseline serum HBV pgRNA levels were found to be strong predictors of HBeAg seroclearance after 6 months of Tenofovir treatment. The study presents a novel RT-PCR assay that allows accurate measurement of plasma HBV pgRNA in chronic hepatitis B patients, even in the presence of excess HBV DNA. The assay is highly selective and represents a significant advancement with potential for further breakthroughs in understanding the clinical significance of HBV pgRNA., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Current therapies to effectively treat long-bone defects and extensive bone tissue loss remains limited. In this study, we created a new bone substitute by integrating advanced technologies such as structure patterning, controlled release of a bone growth factor and conjugation system for clinically effective bone regeneration. This novel bioactive bone substitute was evaluated for its safety and efficacy using a rabbit ulna model., Methods: A three dimensional bone patterned cylindrical structure with 1.5 cm in length and 5 mm in diameter was printed using poly(L-lactic acid)(PLLA) as a weight-bearing support and space-filling scaffold. And a bone morphogenetic protein 2 (BMP2) was employed to enhance bone regeneration, and coated to a 3D PLLA using alginate catechol and collagen to prolong the release kinetics. This novel bone substitute (BS)was evaluated for its physico-chemical and biological properties in vitro, and histological analysis and radiographical analysis such as X-ray, CT and micro-CT image analysis were performed to evaluate new bone formation in vivo., Results: The BS possesses an ideal shape and mechanically suitable proeperties for clinical use, with an easy-to-grab and break-resistant design at both ends, 80 ± 10 MPa of compression strength, and BMP2 release for two months. Histological analysis demonstrated the biocompability of BS with minimal inflammation and immune response, and X-ray, CT and micro-CT demonstrated effective new bone formation in rabbit ulna defect model., Conclusion: The preclinical study of a novel bioactive bone substitute has shown its safe and effective properties in an animal model suggesting its clinical potential., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

Background: The objective of this study was to investigate differences in oncologic outcomes of patients with pancreas cancer according to natural killer cell activity (NKA)., Methods: A total of 118 patients who underwent curative resection for primary pancreas cancer in two hospitals were analyzed. NKA change pattern was analyzed. Difference in disease-free survival or overall survival was investigated by dividing subjects into two groups based on a normal NKA value for each period., Results: NKA value decreased after surgery compared to the value measured at admission. It recovered to normal levels at 5 weeks postoperatively. The low NKA (less than 250 pg/mL) group at admission, 5 weeks postoperatively, and before 1st chemotherapy had significantly poorer disease-free survival than the normal NKA group. In multivariate analysis, NKA values less than 250 pg/mL at admission (odds ratio = 2.267, p = 0.023) and N 1 or N2 category (odds ratio = 2.478, p = 0.023) were significant factors associated with recurrence after curative resection., Conclusions: NKA in patients with pancreatic cancer demonstrated noticeable changes after surgery. Immunologically predisposed patients with a low NKA value had a high risk of early recurrence and a poor prognosis, although pancreatic cancer was surgically removed., (© 2023 Wiley Periodicals LLC.)

ZSM-5 zeolite was successfully synthesized from bentonite clay sourced from Lam Dong Province, Vietnam, using the hydrothermal method at 170 °C for 18 h. The synthesized ZSM-5 (SiO 2 /Al 2 O 3 ratio ~ 34) exhibited a single phase with high crystallinity (91.8%), and a clear and uniform shape. In a detailed examination of the synthesized material's Pb(II) adsorptive capacity, various factors were taken into account, including pH, interaction time, ionic strength, and the amount of adsorbent. Isotherms and kinetics were examined to elucidate the uptake behavior. Study results suggested that Pb(II) ion uptake by ZSM-5 was most appropriately described by the Sips isotherm and intraparticle diffusion kinetic models. The calculated maximum monolayer adsorption capacity according to the Langmuir isotherm model was 48.36 mg/g. Furthermore, the adsorption mechanisms of Pb(II) on ZSM-5 involving electrostatic interactions, ion exchange, and diffusion into pores were demonstrated using the analytical techniques before and after Pb(II) adsorption. These findings demonstrate that ZSM-5 synthesized from bentonite clay exhibits an excellent adsorption capacity for Pb(II), resulting in promising applications for treating drinking water or aqueous industrial waste containing Pb(II) ions., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Drimane-type sesquiterpenes (DTSs) are significant terpenoid natural products characterized by their unique C 15 bicyclic skeleton. They are produced by various organisms including plants, fungi, bacteria and marine organisms, and exhibit a diverse array of bioactivities. These bioactivities encompass antifeedant, anti-insecticidal, anti-bacterial, anti-fungal, anti-viral and anti-proliferative properties. Some DTSs contribute to the pungent flavor found in herb plants like water pepper, while others serve as active components responsible for the anti-cancer activities observed in medicinal mushrooms such as (-)-antrocin from Antrodia cinnamomea. Recently, DTS synthases have been identified in various organisms, biosynthesizing drimenol, drim-8-ene-11-ol and (+)-albicanol, which all possess the characteristic drimane skeleton. Interestingly, despite these enzymes producing chemical molecules with a drimane scaffold, they exhibit minimal amino acid sequence identity across different organisms. This Concept article focuses on the discovery of DTS synthases and the tailoring enzymes generating the chemical diversity of drimane natural products. We summarize and discuss their key features, including the chemical mechanisms, catalytic motifs and functional domains employed by these terpene synthases to generate DTS scaffolds., (© 2023 Wiley-VCH GmbH.)

Alzheimer's disease (AD) is a complex multifactorial disorder that poses a substantial burden on patients, caregivers, and society. Considering the increased aging population and life expectancy, the incidence of AD will continue to rise in the following decades. However, the molecular pathogenesis of AD remains controversial, superior blood-based biomarker candidates for early diagnosis are still lacking, and effective therapeutics to halt or slow disease progression are urgently needed. As powerful genetic regulators, microRNAs (miRNAs) are receiving increasing attention due to their implications in the initiation, development, and theranostics of various diseases, including AD. In this review, we summarize miRNAs that directly target microtubule-associated protein tau (MAPT), amyloid precursor protein (APP), and β-site APP-cleaving enzyme 1 (BACE1) transcripts and regulate the alternative splicing of tau and APP. We also discuss related kinases, such as glycogen synthase kinase (GSK)-3β, cyclin-dependent kinase 5 (CDK5), and death-associated protein kinase 1 (DAPK1), as well as apolipoprotein E, that are directly targeted by miRNAs to control tau phosphorylation and amyloidogenic APP processing leading to Aβ pathologies. Moreover, there is evidence of miRNA-mediated modulation of inflammation. Furthermore, circulating miRNAs in the serum or plasma of AD patients as noninvasive biomarkers with diagnostic potential are reviewed. In addition, miRNA-based therapeutics optimized with nanocarriers or exosomes as potential options for AD treatment are discussed.

Emerging evidence has demonstrated that using a new manufacturing technology to produce γ-aminobutyric acid (GABA)-fortified oolong (GO) tea could relieve human stress and exert versatile physiological benefits. The purpose of this human study was to investigate the therapeutic effects of daily GO tea consumption on improvements in blood pressure, relaxation-related brain waves, and quality of life (QOL) over a period of 28 consecutive days. Total polyphenols, major catechins, and free amino acids were analyzed via an HPLC assay. Changes in heart rate, blood pressure, α brain waves (index of relaxation), and the eight-item QOL score were investigated on days 0, 7, 14, 21, and 28. The chemical analysis results showed that GO tea contained the most abundant amino acids and GABA, contributing to the relaxation activity. Among all study participants, the daily consumption of GO tea could reduce systolic blood pressure on day 21 and diastolic blood pressure on day 28 ( p < 0.05 for both). For participants with pre-hypertension, GO tea could effectively reduce heart rate and systolic and diastolic blood pressure on day 28 ( p < 0.05). At the end of the study, incremental changes in alpha brain waves and QOL scores were also demonstrated ( p < 0.05 for both). This study suggests that GO tea might potentially serve as a natural source for alternative therapy to improve blood pressure, stress relief, and QOL.

The high expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the emergence of multidrug resistance (MDR) in individuals afflicted with either solid tumors or blood cancers. MDR poses a major impediment in the realm of clinical cancer chemotherapy. Recently, substantial endeavors have been dedicated to identifying bioactive compounds isolated from nature capable of counteracting ABCG2-mediated MDR in cancer cells. Imperatorin, a natural coumarin derivative renowned for its diverse pharmacological properties, has not previously been explored for its impact on cancer drug resistance. This study investigates the chemosensitizing potential of imperatorin in ABCG2-overexpressing cancer cells. Experimental results reveal that at sub-toxic concentrations, imperatorin significantly antagonizes the activity of ABCG2 and reverses ABCG2-mediated MDR in a concentration-dependent manner. Furthermore, biochemical data and in silico analysis of imperatorin docking to the inward-open conformation of human ABCG2 indicate that imperatorin directly interacts with multiple residues situated within the transmembrane substrate-binding pocket of ABCG2. Taken together, these results furnish substantiation that imperatorin holds promise for further evaluation as a potent inhibitor of ABCG2, warranting exploration in combination drug therapy to enhance the effectiveness of therapeutic agents for patients afflicted with tumors that exhibit high levels of ABCG2.

Phase-change random-access memory is a promising non-volatile memory technology. However repeated phase-change operations can cause durability issues owing to defects formed by long-distance atom diffusion. To mitigate these issues, phase-change heterostructure (PCH) devices with confinement material (CM) layers based on transition metal dichalcogenides (TMDs) such as TiTe 2 have been proposed. This study implements PCH devices with additional TMDs, including NiTe 2 and MoTe 2 , alongside TiTe 2 , and analyzes their characteristics by examining the differences in the CM layers. The results show that the NiTe 2 -based PCH device demonstrates a RESET current of 1.4 mA, 38% lower than that of the TiTe 2 -based device, enabling low-power operation. Furthermore, the MoTe 2 -based PCH device exhibits a cycling endurance exceeding 10 7 cycles, a five-fold improvement in durability compare with the TiTe 2 -based device. The performance differences observe in each PCH device can be attributed to the variation in the material properties, such as the cohesive energy and electrical conductivity, of the TMDs used as the CM layer. These results provide critical clues to improve the performance and reliability of conventional PCH memory devices., (© 2023 Wiley-VCH GmbH.)

Background: There is a clinical need to identify patients with an elevated PSA who would benefit from prostate biopsy due to the presence of clinically significant prostate cancer (CSCaP). We have previously reported the development of the MiCheck® Test for clinically significant prostate cancer. Here, we report MiCheck's further development and incorporation of the Roche Cobas standard clinical chemistry analyzer., Objectives: To further develop and adapt the MiCheck® Prostate test so it can be performed using a standard clinical chemistry analyzer and characterize its performance using the MiCheck-01 clinical trial sample set., Design, Settings, and Participants: About 358 patient samples from the MiCheck-01 US clinical trial were used for the development of the MiCheck® Prostate test. These consisted of 46 controls, 137 non-CaP, 62 non-CSCaP, and 113 CSCaP., Methods: Serum analyte concentrations for cellular growth factors were determined using custom-made Luminex-based R&D Systems multi-analyte kits. Analytes that can also be measured using standard chemistry analyzers were examined for their ability to contribute to an algorithm with high sensitivity for the detection of clinically significant prostate cancer. Samples were then re-measured using a Roche Cobas analyzer for development of the final algorithm., Outcome Measurements and Statistical Analysis: Logistic regression modeling with Monte Carlo cross-validation was used to identify Human Epidydimal Protein 4 (HE4) as an analyte able to significantly improve the algorithm specificity at 95% sensitivity. A final model was developed using analyte measurements from the Cobas analzyer., Results: The MiCheck® logistic regression model was developed and consisted of PSA, %free PSA, DRE, and HE4. The model differentiated clinically significant cancer from no cancer or not-clinically significant cancer with AUC of 0.85, sensitivity of 95%, and specificity of 50%. Applying the MiCheck® test to all evaluable 358 patients from the MiCheck-01 study demonstrated that up to 50% of unnecessary biopsies could be avoided while delaying diagnosis of only 5.3% of Gleason Score (GS) ≥3+4 cancers, 1.8% of GS≥4+3 cancers and no cancers of GS 8 to 10., Conclusions: The MiCheck® Prostate test identifies clinically significant prostate cancer with high sensitivity and negative predictive value (NPV). It can be performed in a clinical laboratory using a Roche Cobas clinical chemistry analyzer. The MiCheck® Prostate test could assist in reducing unnecessary prostate biopsies with a marginal number of patients experiencing a delayed diagnosis., Competing Interests: Declaration of Competing Interest The authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Neal D. Shore has neither equity nor salary with Minomic. The author has received honorarium as a consultant/advisor., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this study, the immunomodulatory and antioxidant activity of fermented Caulerpa microphysa byproduct (FCMB) by Bacillus subtilis was evaluated, and its potential as a feed additive for white shrimp (Litopenaeus vannamei) was explored. In vitro experiments showed that the FCMB supernatant contained polysaccharides, polyphenols and flavonoids, and exhibited antioxidant properties as assessed by various antioxidant assays. Additionally, the FCMB supernatant was found to increase the production rate of reactive oxygen species and the activity of phenoloxidase in hemocytes in vitro. Furthermore, the results of the in vivo feeding trial showed that dietary 5 g kg -1 FCMB significantly improved the weight gain and specific growth rate of white shrimp after 56 days of feeding. Although there were no significant differences in total hemocyte count, phagocytosis, superoxide anion production rate, and phenoloxidase activity among the experimental groups, upregulation of immune-related genes was observed, particularly in the hepatopancreas and hemocytes of shrimps fed with 5 g or 50 g FCMB per kg feed, respectively. In the pathogen challenge assay, white shrimp fed with 5 % FCMB exhibited a higher survival rate compared to the control group following Vibrio parahaemolyticus challenge. Therefore, it is concluded that the fermented byproduct of C. microphysa, FCMB, holds potential as a feed additive for enhancing the growth performance and disease resistance against V. parahaemolyticus in white shrimp., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Indigenous peoples globally are at increased risk of COVID-19-associated morbidity and mortality. However, data that describe immune responses to SARS-CoV-2 infection in Indigenous populations are lacking. We evaluated immune responses in Australian First Nations peoples hospitalized with COVID-19. Our work comprehensively mapped out inflammatory, humoral and adaptive immune responses following SARS-CoV-2 infection. Patients were recruited early following the lifting of strict public health measures in the Northern Territory, Australia, between November 2021 and May 2022. Australian First Nations peoples recovering from COVID-19 showed increased levels of MCP-1 and IL-8 cytokines, IgG-antibodies against Delta-RBD and memory SARS-CoV-2-specific T cell responses prior to hospital discharge in comparison with hospital admission, with resolution of hyperactivated HLA-DR + CD38 + T cells. SARS-CoV-2 infection elicited coordinated ASC, Tfh and CD8 + T cell responses in concert with CD4 + T cell responses. Delta and Omicron RBD-IgG, as well as Ancestral N-IgG antibodies, strongly correlated with Ancestral RBD-IgG antibodies and Spike-specific memory B cells. We provide evidence of broad and robust immune responses following SARS-CoV-2 infection in Indigenous peoples, resembling those of non-Indigenous COVID-19 hospitalized patients., (© 2023 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

Background: Density notification laws require notifying women of dense breasts with dense breast prevalence varying by race/ethnicity. We evaluated whether differences in body mass index (BMI) account for differences in dense breasts prevalence by race/ethnicity., Methods: Prevalence of dense breasts (heterogeneously or extremely dense) according to Breast Imaging Reporting and Data System and obesity (BMI > 30 kg/m2) were estimated from 2,667,207 mammography examinations among 866,033 women in the Breast Cancer Surveillance Consortium (BCSC) from January 2005 through April 2021. Prevalence ratios (PR) for dense breasts relative to overall prevalence by race/ethnicity were estimated by standardizing race/ethnicity prevalence in the BCSC to the 2020 U.S. population, and adjusting for age, menopausal status, and BMI using logistic regression., Results: Dense breasts were most prevalent among Asian women (66.0%) followed by non-Hispanic/Latina (NH) White (45.5%), Hispanic/Latina (45.3%), and NH Black (37.0%) women. Obesity was most prevalent in Black women (58.4%) followed by Hispanic/Latina (39.3%), NH White (30.6%), and Asian (8.5%) women. The adjusted prevalence of dense breasts was 19% higher [PR = 1.19; 95% confidence interval (CI), 1.19-1.20] in Asian women, 8% higher (PR = 1.08; 95% CI, 1.07-1.08) in Black women, the same in Hispanic/Latina women (PR = 1.00; 95% CI, 0.99-1.01), and 4% lower (PR = 0.96; 95% CI, 0.96-0.97) in NH White women relative to the overall prevalence., Conclusions: Clinically important differences in breast density prevalence are present across racial/ethnic groups after accounting for age, menopausal status, and BMI., Impact: If breast density is the sole criterion used to notify women of dense breasts and discuss supplemental screening it may result in implementing inequitable screening strategies across racial/ethnic groups. See related In the Spotlight, p. 1479., (©2023 American Association for Cancer Research.)

High-quality molecular markers are essential for marker-assisted selection to accelerate breeding progress. Compared with diploid species, recently diverged polyploid crop species tend to have highly similar homeologous subgenomes, which is expected to limit the development of broadly applicable locus-specific single-nucleotide polymorphism (SNP) assays. Furthermore, it is particularly challenging to make genome-wide marker sets for species that lack a reference genome. Here, we report the development of a genome-wide set of kompetitive allele specific PCR (KASP) markers for marker-assisted recurrent selection (MARS) in the tetraploid minor crop perilla. To find locus-specific SNP markers across the perilla genome, we used genotyping-by-sequencing (GBS) to construct linkage maps of two F2 populations. The two resulting high-resolution linkage maps comprised 2326 and 2454 SNP markers that spanned a total genetic distance of 2133 cM across 16 linkage groups and 2169 cM across 21 linkage groups, respectively. We then obtained a final genetic map consisting of 22 linkage groups with 1123 common markers from the two genetic maps. We selected 96 genome-wide markers for MARS and confirmed the accuracy of markers in the two F2 populations using a high-throughput Fluidigm system. We confirmed that 91.8% of the SNP genotyping results from the Fluidigm assay were the same as the results obtained through GBS. These results provide a foundation for marker-assisted backcrossing and the development of new varieties of perilla., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In pancreaticoduodenectomy (PD), the duodenum and upper jejunum responsible for iron absorption are removed, which can lead to massive hemorrhage during surgery and cause iron deficiency anemia after PD. The aim of this study was to evaluate overall changes in hematologic profiles of patients who underwent pancreaticoduodenectomy. Effect of preoperative intravenous iron treatment on recovery of anemia after surgery was also investigated., Methods: From March 2021 to December 2021, patients who underwent curative PD at our institution due to periampullary lesions were enrolled. They were divided into two groups according to whether or not iron was administered before surgery. In the IV iron group, all patients had been routinely administered with 1000 mg of ferric carboxymaltose intravenously once about 3-7 days before the operation day. Contrarily, patients in the control group did not receive intravenous iron before PD. Changes in hematological profile were measured preoperatively and at 5, 14, and 30 days postoperatively. Clinical results of the two groups were compared and analyzed. Additionally, a subgroup analysis was performed for selected non-anemic patients who had preoperative hemoglobin level of 12.0 g/dl or higher to compare changes in hematologic profiles between the two groups., Results: Thirty patients of the IV iron group and 34 patients of the control group were analyzed. Although no difference was observed in postoperative complications or mortality, hemoglobin and iron levels were recovered significantly faster at two weeks postoperatively in the IV iron group than in the control group. Iron levels were significantly higher in the IV iron group throughout the postoperative period. In subgroup analysis conducted for non-anemic patients, hemoglobin levels were recovered significantly faster and maintained higher in the IV iron group throughout the postoperative period, although baseline levels of hemoglobin were similar between the two groups. In addition, the length of intensive care unit stay was significantly shorter in the IV iron group than in the control group., Conclusions: Preoperative intravenous iron treatment might be effective in facilitating recovery of hematologic profiles of patients during the recovery period after PD regardless of the presence of preoperative anemia, thus preventing postoperative iron deficiency anemia., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Kinetic studies play an instrumental role in determining the most appropriate reaction rate model for industrial-scale applications. This study focuses on the kinetics of methylene blue (MB) adsorption from aqueous solutions by biochar derived from jackfruit peel. Various kinetic models, including pseudo-first-order (PFO), pseudo-second-order (PSO), intra-diffusion, and Elovich models, were applied to study MB adsorption kinetics of jackfruit peel biochar. The experiments were performed with two initial concentrations of MB (24.23 mg/L and 41.42 mg/L) over a span of 240 min. Our findings emphasized that the Elovich model provided the best fit of the experimental data for MB adsorption. When compared to other materials, biochar from jackfruit peel emerges as an eco-friendly adsorbent for dye decolorization, with potential applications in the treatment of environmental pollution., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3-49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04-3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11-3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19-9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23-4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches., (© 2023. Springer Nature Limited.)

This paper presents a study of the propagation of surface acoustic waves in a single and periodic array of metal strip overlays on the surface of layered substrates. Responses of reflected and transmitted surface acoustic waves due to various geometric design parameters of the grating arrays are investigated. An eight-dimensional matrix formulation based on Stroh formalism is adopted to analyze wave propagation in piezoelectric layered media. The dispersion curves for aluminum-zinc oxide films on glass substrates are determined using the surface impedance tensor method. A transfer matrix in terms of the state vectors in cooperation with continuity conditions on the edges of the grating array is used to determine the reflectivity and transmittance of the horizontally propagating surface acoustic waves. The analysis and simulation results show that when the surface acoustic wave is obliquely incident on an array of gratings and the strip width is equal to the gap between strips, the constructive interference of the reflected wave occurs at odd multiples of the strip width to a wavelength ratio of 0.25. When the strip width is unequal to the gap, the constructive interference of the reflected wave is an odd multiple of the strip width to a wavelength ratio of 0.5. An increase in the number of strips concentrates the reflectivity's extreme frequencies, and an increase in the strip height increases the bandwidth of the extreme frequencies. Both of these increases strengthen the reflected wave's constructive interferences.

Galectin-1 is a β-galactoside-binding lectin that has been implicated as a suppressive molecule in cancer and autoimmune diseases. Gal-1 has known immunomodulatory activity and was found to be expressed on regulatory T cells, leading to the potential for targeted immunotherapies. Anti-Gal-1 monoclonal antibodies were generated in this study using classical hybridoma techniques. MAb 6F3 was found to bind to Gal-1 by Western blot and ELISA. Flow cytometry was used to determine cell surface and intracellular binding of mAb 6F3 to Gal-1 in PBMC-derived Tregs and tumor cells, including Treg-like cell lines. These results suggest mAb 6F3 may be used to further study Gal-1 protein expression and function., Competing Interests: Declaration of competing interest THH has received research funding from Novartis and has served on advisory boards for Exelixis, Genentech, EMD-Serono, Ipsen, Cardinal Health, Surface Therapeutics, and Pfizer. The other authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The locus coeruleus (LC) is a brainstem region associated with broad neural arousal because of norepinephrine production, but it has increasingly been associated with specific cognitive processes. These include sustained attention, with deficits associated with various neuropsychological disorders. Neural models of attention deficits have focused on interrupted dynamics between the salience network (SAL) with the frontoparietal network, which has been associated with task-switching and processing of external stimuli, respectively. Conflicting findings for these regions suggest the possibility of upstream signaling leading to attention dysfunction, and recent research suggests LC involvement. In this study, resting-state functional connectivity and behavioral performance on an attention task was examined within 584 individuals. Analysis revealed significant clusters connected to LC activity in the SAL. Given previous findings that attention deficits may be caused by SAL network switching dysfunctions, findings here further suggest that dysfunction in LC-SAL connectivity may impair attention., (© 2023 Massachusetts Institute of Technology.)

Background: The depth of connective tissue window in the side of a recipient nerve in reverse end-to-side transfers (RETS) remains controversial., Objective: To test whether the depth of connective tissue disruption influences the efficiency of donor axonal regeneration in the context of RETS., Methods: Sprague-Dawley rats (n = 24) were assigned to 1 of the 3 groups for obturator nerve to motor femoral nerve RETS: group 1, without epineurium opening; group 2, with epineurium only opening; and group 3, with epineurium and perineurium opening. Triple retrograde labeling was used to assess the number of motor neurons that had regenerated into the recipient motor femoral branch. Thy1-GFP rats (n = 8) were also used to visualize the regeneration pathways in the nerve transfer networks at 2- and 8-week time point using light sheet fluorescence microscopy., Results: The number of retrogradely labeled motor neurons that had regenerated distally toward the target muscle was significantly higher in group 3 than that in groups 1 and 2. Immunohistochemistry validated the degree of connective tissue disruption among the 3 groups, and optical tissue clearing methods demonstrated donor axons traveling outside the fascicles in groups 1 and 2 but mostly within the fascicles in group 3., Conclusion: Creating a perineurial window in the side of recipient nerves provides the best chances of robust donor axonal regeneration across the RETS repair site. This finding aids nerve surgeons by confirming that a deep window should be undertaken when doing a RETS procedure., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Plants are challenged by various pathogens throughout their lives, such as bacteria, viruses, fungi, and insects; consequently, they have evolved several defense mechanisms. In addition, plants have developed localized and systematic immune responses due to biotic and abiotic stress exposure. Animals are known to activate DNA damage responses (DDRs) and DNA damage sensor immune signals in response to stress, and the process is well studied in animal systems. However, the links between stress perception and immune response through DDRs remain largely unknown in plants. To determine whether DDRs induce plant resistance to pathogens, Arabidopsis plants were treated with bleomycin, a DNA damage-inducing agent, and the replication levels of viral pathogens and growth of bacterial pathogens were determined. We observed that DDR-mediated resistance was specifically activated against viral pathogens, including turnip crinkle virus (TCV). DDR increased the expression level of pathogenesis-related (PR) genes and the total salicylic acid (SA) content and promoted mitogen-activated protein kinase signaling cascades, including the WRKY signaling pathway in Arabidopsis. Transcriptome analysis further revealed that defense- and SA-related genes were upregulated by DDR. The atm-2atr-2 double mutants were susceptible to TCV, indicating that the main DDR signaling pathway sensors play an important role in plant immune responses. In conclusion, DDRs activated basal immune responses to viral pathogens.

Background/aims: Due to the possible metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia., Methods: Medical records were reviewed retrospectively in patients who underwent endoscopic resection for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into two groups; annual surveillance vs. biannual surveillance. The incidence of metachronous gastric neoplasia was identified, and the risk factors for metachronous gastric neoplasia were investigated., Results: Among the 1,533 patients who underwent endoscopic resection for gastric neoplasia, 677 patients were enrolled in this study (annual surveillance 302, biannual surveillance 375). Metachronous gastric neoplasia was observed in 61 patients (annual surveillance 26/302, biannual surveillance 32/375, P = 0.989), and metachronous gastric adenocarcinoma was observed in 26 patients (annual surveillance 13/302, biannual surveillance 13/375, P = 0.582). All the lesions were removed by endoscopic resection successfully. In a multivariate analysis, severe atrophic gastritis on gastroscopy was an independent risk factor for metachronous gastric adenocarcinoma (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P = 0.008)., Conclusions: Meticulous observation to detect the metachronous gastric neoplasia is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after endoscopic resection for gastric neoplasia. Annual surveillance gastroscopy might be enough after endoscopic resection for gastric neoplasia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The functional complexity of the central nervous system (CNS) is unparalleled in living organisms. It arises from neural crest-derived cells that migrate by the exact route, leading to the formation of a complex network of neurons and glial cells. Recent studies have shown that novel crosstalk exists between the Notch1 and Nrf2 pathways and is associated with many neurological diseases. The Notch1-Nrf2 axis may act on nervous system development, and the molecular mechanism has recently been reported. In this review, we summarize the essential structure and function of the CNS. The significance of interactions between signaling pathways and between developmental processes like proliferation, apoptosis and migration in ensuring the correct development of the CNS is also presented. We primarily focus on research concerning possible mechanism of interaction between Notch1 and Nrf2 and the functions of Notch1-Nrf2 in neurons. There may be a direct interaction between Notch1 and NRF2, which is closely related to the crosstalk that occurs between them. The significance and potential applications of the Notch1-Nrf2 axis in abnormal development of the nervous system are been highlighten. We also discuss the molecular mechanisms by which the Notch1-Nrf2 axis controls the apoptosis, antioxidant pathway and differentiation of neurons to modulate the development of the nervous system. This information will lead to a better understanding of Notch1-Nrf2 axis signaling pathways in the nervous system and may facilitate the development of new therapeutic strategies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla , Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.

Density functional theory (DFT) calculations were utilized to investigate the electrocatalytic potential of single boron (B) atom doping in defective ReS 2 monolayers as an active site. Our investigation revealed that B-doped defective ReS 2 , containing S and S-Re-S defects, demonstrated remarkable conductivity, and emerged as an exceptionally active catalyst for nitrogen reduction reactions (NRR), exhibiting limiting potentials of 0.63 and 0.53 V, respectively. For both cases, we determined the potential by examining the hydrogenation of adsorbed N 2 * to N 2 H*. Although the competing hydrogen evolution reaction (HER) process appeared dominant in the S-Re-S defect case, its impact was minimal. The outstanding NRR performance can be ascribed to the robust chemical interactions between B and N atoms. The adsorption of N 2 on B weakens the N-N bond, thereby facilitating the formation of NH 3 . Moreover, we verified the selectivity and stability of the catalysts for NRR. Our findings indicate that B-doped defective ReS 2 monolayers hold considerable promise for electrocatalysis in a variety of applications.

The comprehension of silicate oligomer formation during the initial stage of zeolite synthesis is of significant importance. In this study, we investigated the effect of chloride ions (Cl - ) on silicate oligomerization using ab initio molecular dynamics simulations with explicit water molecules. The results show that the presence of Cl - increases the free energy barriers of all reactions compared to the case without the anion. The formation of the 4-ring structure has the lowest free energy barrier (73 kJ/mol), while the formation of the 3-ring structure has the highest barrier (98 kJ/mol) in the presence of Cl - . These findings suggest that Cl - suppresses the formation of 3-rings and favors the formation of larger oligomers in the process of zeolite synthesis. Our study provides important insights into the directing role of Cl - in silicate oligomerization by regulating thermodynamic and kinetic parameters. An important point to consider is the impact of the anion on aqueous reactions, particularly in altering the hydrogen bond network around reactive species. These results also provide a basis for further studies of the formations of larger silicate oligomers in solution.

ATP-binding cassette transporters, including ABCB1 (P-glycoprotein) and ABCG2 (BCRP/MXR/ABCP), are pivotal in multidrug resistance (MDR) development in cancer patients undergoing conventional chemotherapy. The absence of approved therapeutic agents for multidrug-resistant cancers presents a significant challenge in effectively treating cancer. Researchers propose repurposing existing drugs to sensitize multidrug-resistant cancer cells, which overexpress ABCB1 or ABCG2, to conventional anticancer drugs. The goal of this study is to assess whether furmonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor overcomes drug resistance mediated by ABCB1 and ABCG2 transporters. Furmonertinib stands out due to its ability to inhibit drug transport without affecting protein expression. The discovery of this characteristic was validated through ATPase assays, which revealed interactions between furmonertinib and ABCB1/ABCG2. Additionally, in silico docking of furmonertinib offered insights into potential interaction sites within the drug-binding pockets of ABCB1 and ABCG2, providing a better understanding of the underlying mechanisms responsible for the reversal of MDR by this repurposed drug. Given the encouraging results, we propose that furmonertinib should be explored as a potential candidate for combination therapy in patients with tumors that have high levels of ABCB1 and/or ABCG2. This combination therapy holds the potential to enhance the effectiveness of conventional anticancer drugs and presents a promising strategy for overcoming MDR in cancer treatment.

Aspacochioside C (ACC) is a steroidal saponin isolated from Asparagus cochinchinensis. Steroidal saponins, such as pseudoprotodioscin and dioscin, are known to inhibit melanogenesis, but the role of ACC in melanogenesis remains unknown. Due to the toxic effect of the commonly used skin whitening agents like arbutin, kojic acid and α-lipoic acid alternative plant products are recentlybeen studied for their anti-hypergmentation effect. This study explores the role of ACC in melanogenesis in both in vivo and in vitro models. Here, we for the first time demonstrate that ACC attenuated α-MSH- and UVB-induced eumelanin production by inhibiting tyrosinase-related protein (TRP)-2 protein expression in both murine B16F10 and human melanoma MNT1 cells. However, ACC had no significant effect on pheomelanin concentration. ACC also decreased the pigmentation density in zebrafish embryos, which indicates that ACC targets TRP2 and inhibits eumelanin synthesis. Our results demonstrate that ACC inhibits TRP2, thereby attenuating eumelanin synthesis both in in vitro and in vivo zebrafish model. Therefore, ACC can potentially be used as an anti-melanogenic agent for both aesthetic and pharmaceutical purposes., (© 2023. Springer Nature Limited.)

In this study, we assessed the controlled synthesis and efficacy of surface-enhanced Raman scattering (SERS) on two distinct types of star-like Au@Ag core-shell nanoarrays. These nanoarrays were designed based on gold nanostars (AuNSs), which were synthesized with and without CTAB surfactant (AuNSs-CTAB and AuNSs-FS, respectively). The AuNS-FS nanoparticles were synthesized via a novel modification process, which helped overcome the previous limitations in the free-surfactant preparation of AuNSs by significantly increasing the number of branches, increasing the sharpness of the branches and minimizing the adsorption of the surfactant on the surface of AuNSs. Furthermore, the differences in the size and morphology of these AuNSs in the created nanoarrays were studied. To create the nanoarrays, a three-step method was employed, which involved the controlled synthesis of gold nanostars, covering them with a silver layer (AuNSs-FS@Ag and AuNSs-CTAB@Ag), and finally self-assembling the AuNS@Ag core-shelled nanoparticles via the liquid/liquid self-assembly method. AuNSs-FS@Ag showed higher ability in forming self-assembled nanoarrays than the nanoparticles prepared using CTAB, which can be attributed to the decrease in the repulsion between the nanoparticles at the interface. The nano-substrates developed with AuNSs-FS@Ag possessed numerous "hot spots" on their surface, resulting in a highly effective SERS performance. AuNSs-FS featured a significantly higher number of sharp branches than AuNSs-CTAB, making it the better choice for creating nanoarrays. It is worth mentioning that AuNSs-CTAB did not exhibit the same benefits as AuNSs-FS. The morphology of AuNSs with numerous branches was formed by controlling the seed boiling temperature and adding a specific amount of silver ions. To compare the SERS activity between the as-prepared nano-substrates, i.e. , AuNS-CTAB@Ag and AuNS-FS@Ag self-assembled nanoarrays, low concentrations of crystal violet aqueous solution were characterized. The results showed that the developed AuNSs-FS@Ag could detect CV at trace concentrations ranging from 1.0 ng mL -1 to 10 ng mL -1 with a limit of detection (LOD) of 0.45 ng mL -1 and limit of quantification (LOQ) of 1.38 ng mL -1 . The nano-substrates remained stable for 42 days with a decrease in the intensity of the characteristic Raman peaks of CV by less than 7.0% after storage. Furthermore, the spiking method could detect trace amounts of CV in natural water from the Dong Nai River with concentrations as low as 1 to 100 ng mL -1 , with an LOD of 6.07 ng mL -1 and LOQ of 18.4 ng mL -1 . This method also displayed good reproducibility with an RSD value of 5.71%. To better understand the impact of CTAB stabilization of the Au@Ag star-like nanoparticles on their surface-enhanced Raman scattering (SERS) performance, we conducted density functional theory (DFT) calculations. Our research showed that the preparation of AuNSs-FS@Ag via self-assembly is an efficient, simple, and fast process, which can be easily performed in any laboratory. Furthermore, the research and development results presented herein on nanoarrays have potential application in analyzing and determining trace amounts of organic compounds in textile dyeing wastewater., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Exposure setting is crucial in the formation and propagation of SARS-CoV-2 transmission clusters. In this cohort study, transmission networks of 2 waves were differentiated by exposure setting using territory-wide surveillance data with clinical and laboratory records in Hong Kong. Characteristically, the first wave had resulted from imported cases followed by local transmissions, while the second wave was constituted primarily by local infections. With a 4-fold higher caseload, the second wave featured predominance of epidemiologically linked, local, older and asymptomatic patients with higher viral loads and shorter inpatient days. The 1028 transmission clusters formed 155 cascades composing at least two clusters. Daily and social activities were exposure settings that bridged clusters while residences usually terminated transmission cascades. Regulatory restrictions on social activities extinguished cluster formation in bars, but shifted to private parties in the second wave. The results confirmed that strategic interventions targeting exposure settings could achieve effective epidemic control.

Purpose: To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells., Methods: Observational case report., Results: A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect., Conclusion: To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.

Purpose: Investigate components of care for rotator cuff related shoulder pain in workers' compensation in relation to claim outcomes (claim duration, total medical spend, total claim cost, return to work outcome)., Methods: Engagement with (had care, time to care) four components of care (prescribed exercise, imaging, injections, surgery) were obtained from auditing 189 closed workers' compensation files. Associations were analysed between components of care and claim outcomes., Results: 80% received prescribed exercise, 81% imaging, 42% injection and 35% surgery. Median time to imaging (11 days) was shorter than the prescribed exercise (27 days), with injection at 38 days and surgery 118.5 days. With univariable regression analysis higher age, the involvement of legal representation and the presence of rotator cuff pathology from diagnostic imaging (partial thickness tear or full thickness tear) were all associated with increased claim duration, total medical spend, total claim cost and less successful return to work outcomes. After adjusting for these three associations, having an injection or surgery were both positively associated with longer claim duration and greater medical spend, and surgery with greater total claim costs. In general, longer time to receiving components of care was associated with increased claim duration and reduced odds of returning to full duties at work., Conclusion: Early management was not consistent with clinical guidelines for managing workers' compensation rotator cuff related shoulder pain. This may negatively affect claims outcomes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We compared semen quality and sperm DNA fragmentation in cancer patients who underwent sperm banking and controls who underwent sperm cryopreservation for assisted reproductive technology (ART)., Materials and Methods: A total of 132 men, 65 cancer patients and 67 controls, were prospectively enrolled and performed sperm cryopreservation for fertility preservation from May 2019 to February 2021. Sperm quality was determined by measuring semen volume, sperm concentration, sperm motility, and sperm DNA fragmentation index (DFI). Sperm quality and sperm DFI were compared in cancer patients and controls., Results: The major cancers of the 65 cancer patients were leukemia (26.2%), testicular cancer (23.1%), and lymphoma (20.0%). Sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls. Sperm DFI was significantly higher in cancer patients than in controls (24.32%±15.69% vs. 19.11%±11.63%; p=0.033). After excluding 8 cancer patients who received chemotherapy before sperm banking, sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls, but there was no significant difference in sperm DFI for cancer patients and controls (23.14%±12.79% vs. 19.11%±11.63%; p=0.069)., Conclusions: Sperm quality was lower in cancer patients than in controls. There was no difference in the sperm DFI of cancer patients prior to chemotherapy and men presenting for sperm cryopreservation for ART. We recommend that all men who are planning cancer therapy should be offered sperm banking prior to gonadotoxic chemotherapy as a standard of fertility preservation., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

The objective of this study was to establish a multi-residue quantitative method for the analysis of anthelmintic and antiprotozoal drugs in various livestock products (beef, pork, and chicken) using ultra-high-performance liquid chromatography-tandem mass spectrometry. Each compound performed validation at three different levels i.e., 0.5, 1, and 2× the maximum residue limit according to the CODEX guidelines (CAC/GL 71-2009). This study was conducted according to the modified quick, easy, cheap, effective, rugged, and safe procedure. The matrix-matched calibrations gave correlation coefficients >0.98, and the obtained recoveries were in the range of 60.2%-119.9%, with coefficients of variation ≤32.0%. Furthermore, the detection and quantification limits of the method were in the ranges of 0.03-3.2 and 0.1-9.7 μg/kg, respectively. Moreover, a survey of residual anthelmintic and antiprotozoal drugs was also carried out in 30 samples of beef, pork, and chicken collected in Korea. Toltrazuril sulfone was detected in all three samples. Thus, our results indicated that the developed method is suitable for determining the anthelmintic and antiprotozoal drug contents in livestock products., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

As a consequence of cirrhosis, portal hypertension causes resistance to blood flow and leads to the formation of varices. However, colonic variceal hemorrhages are rarely reported but could be a lethal cause of lower gastrointestinal hemorrhage. Currently, there is no consensus on the management of colonic variceal hemorrhage. Variceal ligation, injection sclerotherapy, transjugular intrahepatic portosystemic shunt placement, and balloon-occluded retrograde transvenous obliteration or a combination of the above therapies have been reported with inconsistent success rates. We advocate considering colonic variceal bleeding as a crucial differential diagnosis of lower gastrointestinal bleeding in cirrhotic patients and initiating time-sensitive, definite operative treatment or combination therapy as soon as possible in colonic variceal patients with life-threatening bleeding events, which are often refractory to conservative treatment.