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Seok Kyu Yoon,1 Kyun-Seop Bae,1 Dong Hyun Hong,2 Seong Su Kim,2 Young Kweon Choi,2 Hyeong-Seok Lim1 1Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea; 2Department of Pharmaceutical Research, iCure Pharmaceutical Incorporated, Seoul, Republic of KoreaCorrespondence: Hyeong-Seok LimDepartment of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul Tel +82-2-3010-4623Fax +82-2-3010-4622Email mdlhs@amc.seoul.krIntroduction: This study characterized the pharmacokinetics (PKs) of a donepezil patch formulation currently under development, using mixed effect modeling analysis, and explored optimal patch dosing regimens in comparison with the donepezil oral formulation.Methods: PK data used in this analysis were from 60 healthy Korean male subjects participating in two Phase I studies, where subjects received single or multiple doses of donepezil of 43.75, 87.5, and 175 mg via patches, and 12 of them received a single oral dose of 10 mg of donepezil, followed by a single dose of donepezil via a patch. Donepezil PKs were analyzed by nonlinear mixed effect modeling using NONMEM software.Results: A well-stirred model with two-compartment distribution and delayed absorption was chosen as the best model for the oral formulation. The PKs of donepezil after the patch applications were best described by a two-compartment linear model with zero-order absorption (D2) and absorption delay. The relative bioavailability (BA) of donepezil after the patch application compared with oral dosing was described to be affected by the duration of patch application.Conclusion: PK simulations based on the chosen PK models suggested that, overall, donepezil exposure in plasma is similar whether with 10 mg of oral donepezil every 24 h or a 175 mg patch every 72 h, and likewise with 5 mg of oral donepezil every 24 h or an 87.5 mg patch every 72 h.Keywords: clinical trial(s), clinical trial simulation(s), pharmacokinetics, pharmacometrics, analysis

Background: Transhepatic arterial chemoembolization (TACE), as a local treatment, has been widely used in the treatment of unresectable liver cancer. The introduction of drug carrier microspheres has brought new hope for the therapeutic effect of TACE. Microspheres can realize the slow release and directional delivery of drugs, reduce systemic toxicity and improve local curative effect., Aim: To compare the effectiveness of traditional transcatheter arterial chemoembolization against microsphere-assisted transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma that is incurable., Methods: We searched the PubMed, Embase, Cochrane Library, and CNKI databases for clinical trials of drug-luting beads TACE (DEB-TACE) vs conventional TACE (cTACE) for the treatment of unresectable liver cancer. We screened references based on inclusion and exclusion criteria and then selected valid data for meta-analysis using RevMan 53 software. The complete response (CR) rate, partial response (PR) rate, postoperative stable disease (SD) rate, and 6-month and 12-month survival rates were compared., Results: A total of 12 articles were included, including 1177 patients, 519 of whom received DEB-TACE and 658 of whom received cTACE. The CR rate in the DEB-TACE group was much greater than that in the cTACE group [relative risk (RR) = 1.42, 95%CI: 1.18-1.72, P = 0.0002]. The 12-month survival rate significantly increased (RR = 1.09; 95%CI: 1.01- 1.17, P = 0.03); the PR rate (RR = 1.13; 95%CI: 0.97-1.30, P = 0.12); the SD rate (RR = 0.82; 95%CI: 0.64-1.05, P = 0.12); and the 6-month survival rate (RR = 1.05; 95%CI: 1.00-1.10, P = 0.07). There was no significant difference ( P < 0.05)., Conclusion: Compared with those of iodized oil TACE, the drug-loaded microspheres tended to have therapeutic advantages., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Awake prone positioning (APP) may be beneficial in patients with respiratory failure who are not receiving mechanical ventilation. Randomized controlled trials of APP have been performed during peak COVID-19 periods in unvaccinated populations, with limited data on compliance or patient acceptability. We aimed to evaluate the efficacy and acceptability of APP in a lower-middle income country in an open-label randomized controlled trial using a dedicated APP implementation team and wearable continuous-monitoring devices., Methods: The trial was performed at a tertiary level hospital in Ho Chi Minh City, Vietnam, recruiting adults (≥18 years) hospitalized with moderate or severe COVID-19 and receiving supplemental oxygen therapy via nasal/facemask systems or high-flow nasal cannula (HFNC). Patients were allocated by a computer-generated random number sequence in a 1:1 ratio to standard care or APP, where a dedicated team provided bedside support. Wearable devices continuously recorded pulse oximetry and body position continuously. Our primary outcome was escalation of respiratory support within 28 days of randomization., Results: Ninety-three patients were enrolled in this study between March 2022 and March 2023. Eighty (86%) patients had received ≥2 doses of SARS-CoV2 vaccine. The study was terminated early because of a reduction in the number of eligible patients. Data from 46 patients allocated to APP and 47 to standard care were available for analysis. At baseline, 19/47 (40%) patients allocated to the standard care group and 14/46 (30%) patients allocated to the APP group received HFNC. Continuous monitoring data were available for all patients monitored with wearable devices. Significantly greater mean daily APP times were achieved in those allocated to APP, however, most achieved less than the target 8 h/day. We did not detect clear differences in the primary outcome (relative risk,RR, 0.85, 95% CI 0.40-1.78, p=0.67) or secondary outcomes, including intubation rate and 28-day mortality. Patients reported prone positioning was comfortable, although almost all patients preferred supine positioning. No adverse events associated with the intervention were observed., Conclusions: APP was not associated with benefit, but there was no sign of harm. Continuous monitoring with wearable devices is both feasible and acceptable for patients. In our population, achieving prolonged APP time was challenging despite a dedicated support team, and patients preferred supine positioning., Clinical Trials Registration: NCT05083130., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Phong NT et al.)

As an essential reaction of water splitting in alkaline solution, the hydrogen evolution reaction (HER) is seriously limited by its ponderous dynamics and the dissolution of Ru. Herein, we propose a strategy for the electrochemical deposition of Ru nanoparticles on the surface of Ag nanowires (Ag NWs) to generate a core-shell Ru@Ag/AgCl catalyst through an accelerated galvanostatic interaction conducted in RuCl 3 solution. The active sites of Ru were precisely controlled by tailoring the number of cycles in cyclic voltammetry (CV). Interestingly, the as-designed Ru@Ag/AgCl-200 electrode maintained its original morphology after 200 CV cycles, demonstrating the high stability of the designed electrocatalyst. The electrochemical performance of the Ru@Ag/AgCl-200 catalyst justifies its excellent HER performance, including a low overpotential of 40.2 mV at a current density of 10 mA cm -2 , small Tafel slope of 53.24 mV dec -1 , and great stability, compared to other control catalysts. Furthermore, the Ru@Ag/AgCl-200 catalyst delivered a low output potential of 1.53 V and sustained long-term stability of 50 h at a current density of 10 mA cm -2 for water splitting. This work provides a framework for accelerated galvanostatic interaction for the controlled synthesis of Ru-based catalysts, which can be used for boosting the HER in alkaline solutions.

Hornworts are the only land plants that employ a pyrenoid to optimize Rubisco's CO 2 fixation, yet hornwort Rubisco remains poorly characterized. Here we assembled the hornwort Anthoceros agrestis Rubisco (AaRubisco) using the Arabidopsis thaliana SynBio expression system and observed the formation of stalled intermediates, prompting us to develop a new SynBio system with A. agrestis cognate chaperones. We successfully assembled AaRubisco and Rubisco from three other hornwort species. Unlike A. thaliana Rubisco, AaRubisco assembly is not dependent on RbcX or Raf2. Kinetic characterization reveals that hornwort Rubiscos exhibit a range of catalytic rates (3-10 s -1 ), but with similar affinity (∼30 μM) and specificity (∼70) for CO 2 . These results suggest that hornwort Rubiscos do not comply with the long-held canonical catalytic trade-off observed in other land plants, providing experimental support that Rubisco kinetics may be phylogenetically constrained. Unexpectedly, we observed a 50% increase in AaRubisco catalytic rates when RbcX was removed from our SynBio system, without any reduction in specificity. Structural biology, biochemistry, and proteomic analysis suggest that subtle differences in Rubisco large-subunit interactions, when RbcX is absent during biogenesis, increases the accessibility of active sites and catalytic turnover rate. Collectively, this study uncovered a previously unknown Rubisco kinetic parameter space and provides a SynBio chassis to expand the survey of other Rubisco kinetics. Our discoveries will contribute to developing new approaches for engineering Rubisco with superior kinetics., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Alveolar bone defects pose a significant challenge in oral clinical treatments, impacting procedures such as dental implants, orthodontics, and oral restoration. Despite their frequent occurrence due to various causes, the effective restoration and reconstruction of alveolar bone defects remain a significant clinical challenge in dentistry. Existing treatments often rely on intrinsic blood coagulation to stabilize bone grafts, but they present limitations such as gradual clotting and reduced effectiveness in patients with coagulation dysfunction. Injectable gel holds promise as an alternative to coagulation-dependent bone graft matrices, but it also faces challenges, including low initial viscosity and dependence on the natural formation of the defect area during the curing process. Here, we present a ceramic-craft-inspired osteogenic (CIO) hydrogel, designed to achieve moldable and curable properties for bone defect regeneration. This injectable paste, composed of gelatin methacrylate (GelMA), nanoclay, and bone grafts, allows for local injection and manual shaping without the need for molds. The shaped hydrogel rapidly crosslinks within 15 s under UV irradiation, providing malleability, strength, and coagulation-independent bone graft stabilization. This approach offers a potential breakthrough in addressing the persistent clinical challenge of alveolar bone defect restoration., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The Eaf6 protein, a conserved component of the NuA4 and NuA3 complexes in yeast and MOZ/MORF complexes in humans, plays crucial roles in transcriptional activation, gene regulation, and cell cycle control. Despite its significance in other organisms, the functional role of Eaf6 in entomopathogenic fungi (EPF) remained unexplored. Here, we investigate the function of BbEaf6, the Eaf6 homolog in the entomopathogenic fungus Beauveria bassiana . We demonstrate that BbEaf6 is predominantly localized in nuclei, similar to its counterpart in other fungi. Deletion of BbEaf6 resulted in delayed conidiation, reduced conidial yield, and altered conidial properties. Transcriptomic analysis revealed dysregulation of the genes involved in asexual development and cell cycle progression in the Δ BbEaf6 mutant. Furthermore, the Δ BbEaf6 mutant exhibited decreased tolerance to various stresses, including ionic stress, cell wall perturbation, and DNA damage stress. Notably, the Δ BbEaf6 mutant displayed attenuated virulence in insect bioassays, accompanied by dysregulation of genes associated with cuticle penetration and haemocoel infection. Overall, our study elucidates the multifaceted role of BbEaf6 in stress response, development, and virulence in B. bassiana , providing valuable insights into the molecular mechanisms governing fungal pathogenesis and potential targets for pest management strategies.

Not available.

Cerebral small vascular disease (CSVD) has a high incidence worldwide, but its pathological mechanisms remain poorly understood due to the lack of proper animal models. The current animal models of CSVD have several limitations such as high mortality rates and large-sized lesions, and thus it is urgent to develop new animal models of CSVD. Ultrasound can activate protoporphyrin to produce reactive oxygen species in a liquid environment. Here we delivered protoporphyrin into cerebral small vessels of rat brain through polystyrene microspheres with a diameter of 15 μm, and then performed transcranial ultrasound stimulation (TUS) on the model rats. We found that TUS did not affect the large vessels or cause large infarctions in the brain of model rats. The mortality rates were also comparable between the sham and model rats. Strikingly, TUS induced several CSVD-like phenotypes such as cerebral microinfarction, white matter injuries and impaired integrity of endothelial cells in the model rats. Additionally, these effects could be alleviated by antioxidant treatment with N-acetylcysteine (NAC). As control experiments, TUS did not lead to cerebral microinfarction in the rat brain when injected with the polystyrene microspheres not conjugated with protoporphyrin. In sum, we generated a rat model of CSVD that may be useful for the mechanistic study and drug development for CSVD., Competing Interests: Declaration of competing interest The authors declare that there is no competing interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Complicated intra-abdominal infections (cIAIs), often caused by multidrug-resistant bacteria such as carbapenem-resistant A. baumannii (CRAB) and carbapenem-resistant Enterobacteriaceae (CRE) are a critical challenge in ICUs. Owing to their high mortality and treatment failure rates, there is an urgent need for effective therapies. This trial will compare eravacycline to tigecycline for treating cIAIs in patients in the ICU, aiming to provide a superior treatment option., Methods: This is a multicenter, single-blind, parallel randomized controlled trial. Adult patients in the ICU with complex abdominal infections who meet the eligibility criteria will be included. The main outcome is the all-cause 30-day mortality of patients in clinically evaluable and microbiologically evaluable populations. Secondary outcomes include the proportion of total responsive patients in the clinically evaluable population at the end of treatment and test of cure visits; the proportion of total responsive patients in the microbiologically evaluable population at the end of treatment and test of cure visits; and ICU hospitalization time and costs. Safety assessments include the incidence of various adverse events and changes in clinical laboratory test results. The subjects will be randomly assigned to receive treatment with either eravacycline or tigecycline at a 1:1 ratio. The all-cause mortality rates of patients treated with eravacycline and TGC were 17.7 and 18.7%, respectively, with an estimated actual mortality rate of 0.95. A total sample size of 262 subjects is required to reach 80% power with an α of 0.05. Considering a 10% loss rate, 292 patients will be enrolled and randomly assigned to the three groups in equal proportions., Ethics and Communication: This trial was approved by the Ethics Committee of Ansteel Group General Hospital. The communication plan includes presentations at scientific conferences, scientific publications, and presentations to the public through nonprofessional media., Clinical Trial Registration: https://clinicaltrials.gov/, ChiCTR2300078646., 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 © 2024 Liu, Guo, Wang, Li, Li, Liu, Yang and Zhang.)

Vibrio parahaemolyticus in seafood and marine environments poses significant health risks, causing gastroenteritis worldwide. Current detection methods fail to differentiate live from dead cells, leading to inaccuracies in food safety assessments. This study introduces a novel method combining cis-diamminedichloroplatinum (CDDP) with direct colorimetric loop-mediated isothermal amplification (LAMP) for rapid and accurate detection of viable V. parahaemolyticus cells in seafood samples. CDDP treatment at 37 °C for 30 min selectively inhibits DNA from dead cells, enhancing the specificity of the assay by ensuring only live cell DNA is amplified. The optimized CDDP-LAMP procedure detects alive V. parahaemolyticus within 1 h, with results observable through a color change. The CDDP-LAMP assay demonstrates excellent specificity, identifying live V. parahaemolyticus cells while excluding dead cells and other bacteria. It shows a detection limit of 2.348 CFU per reaction and successfully detects V. parahaemolyticus in seafood samples across different food matrices. This study is the first to combine CDDP with colorimetric LAMP for direct detecting viable bacteria in food, enhancing specificity by eliminating signals from dead cells. The CDDP-LAMP assay provides a rapid, accurate process for detecting viable V. parahaemolyticus cells, especially in resource-limited settings. It also gives a model for screening different bacterial pathogens, speeding up and improving foodborne illness risk assessments., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background/objectives: Unmet oral health needs of residents in residential aged care facilities (RACFs) arise due to the unique challenges of assessing oral health statuses and maintaining oral healthcare in RACFs. This pilot study assessed the feasibility of using real-time teledentistry under the guidance of a dentist to train RACF staff to undertake an oral health assessment., Methods: An oral health assessment of residents was first conducted by RACF staff at two Queensland, Australia RACFs using the Oral Health Assessment Tool, with an intra-oral camera connected to a laptop, through videoconferencing, under the guidance of a dentist. A survey recorded the views of RACF staff on the acceptability of the teledentistry method. The quality of the images obtained through the camera was assessed by the dentist. Finally, cost-effectiveness was calculated between teledentistry and traditional face-to-face assessments., Results: Sixteen residents (mean age 79.3 ± 8.68 years) and eight staff (mean age 33.3 ± 6.16 years) participated in this study. Both RACF staff and residents found that the real-time teledentistry set-up was user-friendly, while the dentist rated the quality of the images as acceptable for diagnostic purposes. Real-time teledentistry was more cost-effective than bringing a dentist on-site, while taking the RACF residents to an off-site dental office for examination was the most expensive approach., Conclusions: Real-time teledentistry is feasible and cost-effective, and it is an acceptable alternative to a face-to-face clinical exam for oral health assessment in RACFs. This approach could be used in RACFs where wireless internet connectivity is available.

Three uncommon isospongian diterpenoids including a new one, 3-epi-kravanhin A (2), were isolated from the leaves of Amomum tsao-ko. Compounds 2 and 3 dose-dependently promoted GLP-1 secretion on STC-1 cells with promotion ratios of 109.7 % and 186.1 % (60 μM). Mechanism study demonstrated that the GLP-1 stimulative effects of 2 and 3 were closely related with Ca 2+ /CaMKII and PKA pathways, but irrelevant to GPBAR1 and GPR119 receptors. Moreover, compound 1 showed DPP-4 inhibitory activity with an IC 50 value of 311.0 μM. Molecular docking verified the binding affinity of 1 with DPP-4 by hydrogen bonds between the γ-lactone carbonyl (C-15) and Arg61 residue. Bioinformatics study indicated that compound 1 exerted antidiabetic effects by improving inflammation, oxidative stress and insulin resistance. This study first disclosed the presence of isospongian diterpenoids in A. tsao-ko, which showed antidiabetic potency by promoting GLP-1 secretion and inhibiting DPP-4 activity., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (Ir3) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex Ir3 induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex Ir3 promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response in vivo, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Phytochemical studies on the leaves and twigs of Garcinia oligantha Merr. led to the isolation of twelve previously undescribed depsidone derivatives (oliganthdepsidones A-L, 1-12). Their structures were elucidated by extensive spectroscopic analysis including 1 H and 13 C NMR, HSQC, HMBC and NOESY along with HRESIMS. The structures of oliganthdepsidones G and J were finally determined using DFT-NMR chemical shift calculations and DP4+ methods. Cytotoxicity test in four human cancer cell lines indicated that oliganthdepsidone F had relatively strong cytotoxic effect against A375 (melanoma), A549 (lung cancer), HepG2 (liver cancer), and MCF-7 (breast cancer) cell lines with IC 50 of 18.71, 15.44, 10.92, and 15.90 μM, respectively. The dose- and time-dependent antiproliferative effects of oliganthdepsidone F on these cell lines were also observed by CCK-8 test. As determined by fluorescent microscopy and flow cytometry in these cell lines, oliganthdepsidone F could promote cell apoptosis, leading to the inhibition of cell proliferation. The results of wound healing assay and transwell assay showed that oliganthdepsidone F could inhibit the migration and invasion of A549 and MCF-7 cell lines in a concentration-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Evidence regarding the link between long-term ambient ozone (O 3 ) exposure and childhood sleep disorders is little. This study aims to examine the associations between long-term exposure to O 3 and sleep disorders in children. We conducted a population-based cross-sectional survey, including 185,428 children aged 6-18 years in 173 schools across 14 Chinese cities during 2012 and 2018. Parents or guardians completed a checklist using Sleep Disturbance Scale for Children, and O 3 exposure at residential and school addresses was estimated using a satellite-based spatiotemporal model. We used generalized linear mixed models to test the associations with adjustment for factors including socio-demographic variables, lifestyle, meteorology and multiple pollutants. Mean concentrations of O 3 , particulate matter with diameters ≤2.5 mm (PM 2.5 ) and nitrogen dioxide (NO 2 ) were 89.0 μg/m 3 , 42.5 μg/m 3 and 34.4 μg/m 3 , respectively. O 3 and NO 2 concentrations were similar among provinces, while PM 2.5 concentration varied significantly among provinces. Overall, 19.4% of children had at least one sleep disorder. Long-term exposure to O 3 was positively associated with odds of sleep disorders for all subtypes. For example, each interquartile increment in home-school O 3 concentrations was associated with a higher odds ratio for global sleep disorder, at 1.22 (95% confidence interval: 1.18, 1.26). Similar associations were observed for sleep disorder subtypes. The associations remained similar after adjustment for PM 2.5 and NO 2 . Moreover, these associations were heterogeneous regionally, with more prominent associations among children residing in southeast region than in northeast and northwest regions in China. We concluded that long-term exposure to O 3 is positively associated with risks of childhood sleep disorders. These associations varied by geographical region of China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Precise adjusting the band gaps in metal-organic frameworks (MOFs) is crucial for improving their visible-light absorption capacity during photocatalysis, presenting both a formidable challenge and a charming opportunity. This present study employed a symmetry-reduction strategy to pre-design six novel 4-connected ligands with systematic substituents (-NO 2 , -H, - t Bu, -OCH 3 , -OH and -NH 2 ) and synthesized the corresponding pillared-layer Zr-MOFs (NKM-668) retaining the hexaphenylbenzene fragment. Subsequently, the NKM-668 MOFs were transformed into large-π-conjugated hexabenzocoronene-based MOFs (pNKM-668) via the Scholl reaction. These twelve MOFs exhibited broad and tunable band gaps over 1.41 eV (ranging from 3.25 eV to 1.84 eV), and the photocatalytic CO 2 conversion rate raised by 33.2-fold. This study not only enriches the type of hexaphenylbenzene-based MOFs, but also paves the way for nanographene-containing MOFs in the further application of photocatalysis., (© 2024 Wiley-VCH GmbH.)

The photolysis of disulfide bonds is implicated in denaturation of proteins exposed to ultraviolet light. Despite this biological relevance in stabilizing the structure of many proteins, the mechanisms of disulfide photolysis are still contested after decades of research. Herein, we report new insight into the photochemistry of L-cystine in aqueous solution by femtosecond X-ray absorption spectroscopy at the sulfur K-edge. We observe homolytic bond cleavage upon ultraviolet irradiation and the formation of thiyl radicals as the single primary photoproduct. Ultrafast thiyl decay due to geminate recombination proceeds at a quantum yield of >80 % within 20 ps. These dynamics coincide with the emergence of a secondary product, attributed to the generation of perthiyl radicals. From these findings, we suggest a mechanism of perthiyl radical generation from a vibrationally excited parent molecule that asymmetrically fragments along a carbon-sulfur bond. Our results point toward a dynamic photostability of the disulfide bridge in condensed-phase., (© 2024. The Author(s).)

Barrier membranes have been used for the treatment of alveolar bone loss caused by periodontal diseases or trauma. However, an optimal barrier membrane must satisfy multiple requirements simultaneously, which are challenging to combine into a single material. We herein report the design of a bioinspired membrane consisting of three functional layers. The primary layer is composed of clay nanosheets and chitin, which form a nacre-inspired laminated structure. A calcium phosphate mineral layer is deposited on the inner surface of the nacre-inspired layer, while a poly(lactic acid) layer is coated on the outer surface. The composite membrane integrates good mechanical strength and deformability because of the nacre-inspired structure, facilitating operations during the implant surgery. The mineral layer induces the osteogenic differentiation of bone marrow mesenchymal stem cells and increases the stiffness of the membrane, which is an important factor for the regeneration process. The poly(lactic acid) layer can prevent unwanted mineralization on the outer surface of the membrane in oral environments. Cell experiments reveal that the membrane exhibits good biocompatibility and anti-infiltration capability toward connective tissue/epithelium cells. Furthermore, in vitro analyses show that the membrane does not degrade too fast, allowing enough time for bone regeneration. In vivo experiments prove that the membrane can effectively induce better bone regeneration and higher trabecular bone density in alveolar bone defects. This study demonstrates the potential of this bioinspired triple-layered membrane with hierarchical structures as a promising barrier material for periodontal guided tissue regeneration.

Background and Aim: China has used traditional Chinese medicine (TCM) to treat diseases for more than 2000 years. Traditionally, TCMs in medicine cabinets are arranged alphabetically or on the basis of experience, but this arrangement greatly affects dispensing efficiency. However, owing to the unique properties and qualities of TCM, very few automatic approaches or systems have specifically addressed TCM dispensing problems. Therefore, it is necessary to establish a method of optimizing the traditional Chinese medicine placement scheme (TCMPS) via computer algorithms to improve the work efficiency of pharmacists., Methods: A prescription dataset from a hospital in 2022 was obtained, and the association rule algorithm (ARA) was used to calculate the frequency of use for each type of TCM and the associations between different types of TCMs. On the basis of these association and frequency data, the optimal TCMPS was calculated using the simulated annealing algorithm (SAA) and then verified using the prescription dataset from 2023., Results: A total of 10,601 prescriptions were collected in 2022, involving 360 different TCMs, and each prescription contained an average of 9.485 TCMs, with Danggui (3628) being the most frequently used. When the threshold of support was set to 0.05 and the confidence was set to 0.8, 78 couplet medicines used in orthopedics clinics were found through ARA. When the threshold value of support was set to 0, the confidence was set to 0, and the rule length was 2, a total of 129,240 rules were obtained, indicating support between all pairwise TCMs. The TCMPS, calculated using SAA, had a correlation sum of 14.183 and a distance sum of 3.292. The TCMPS was verified using a prescription dataset from 2023 and theoretically improved the dispensing efficiency of pharmacists by approximately 50%., Conclusions: In this study, the ARA and SAA were successfully applied to pharmacies for the first time, and the optimal TCMPS was calculated. This approach not only significantly improves the dispensing efficiency of pharmacists and reduces patient waiting time but also enhances the quality of medical services and patient satisfaction, and provides a valuable reference for the development of smart medicine., (© 2024. The Author(s).)

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon‑carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid β (Aβ)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aβ-induced neuronal damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Corrosion of steel in the marine environment greatly reduces their service life. Polymeric coatings are the most popular anticorrosion technology, but seawater penetration cannot be prohibited because of the distinct stacking structure of the macromolecular chains. In this context, a novel anticorrosive hyperbranched polyurethane-based coating with dopamine (DOPA) at the terminals is prepared herein. The built-in DOPA is able to capture the iron ions released from the corroded substrate and form DOPA-Fe 3+ complexation, which further cooperates with the surrounding seawater and imparts self-passivation, self-delivery and self-healing capabilities to the coating. Under the joint action of these measures, the corrosion of tinplate (serving as the steel model) is reduced to a record-low level (corrosion current = 1 × 10 -9  A cm -2 , corrosion rate = 1 × 10 -5  mm year -1 ). Conceptually, the present dynamic active anticorrosion strategy greatly outperforms the traditional static passive approach, and turns the unfavorable but unavoidable seawater into a favorable factor, which paves the way for the development of long-lasting marine coatings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris., Methods: This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8 : 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts., Results: A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively., Conclusion: Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Patients with aggressive HCC have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic., Approach and Results: The comprehensive proteomic, phosphoproteomic, and ubiquitomic analyses were performed on tumors and adjacent normal liver tissues from 85 patients with HCC. HCCs displayed overexpression of drugable targets CBR1-S151 and CPNE1-S55. COL4A1, LAMC1, and LAMA4 were highly expressed in the disease free survival-poor patients. Phosphoproteomic and ubiquitomic features of HCC revealed cross talk in metabolism and metastasis. Ubiquitomics predicted diverse prognosis and clarified HCC subtype-specific proteomic signatures. Expression of biomarkers TUBA1A, BHMT2, BHMT, and ACY1 exhibited differential ubiquitination levels and displayed high prognostic risk scores, suggesting that targeting these proteins or their modified forms may be beneficial for future clinical treatment. We validated that TUBA1A K370 deubiquitination drove severe HCC and labeled an aggressive subtype of HCCs. TUBA1A K370 deubiquitination was at least partly attributed to protein kinase B-mediated USP14 activation in HCC. Notably, targeting AKT-USP14-TUBA1A complex promoted TUBA1A degradation and blocked liver tumorigenesis in vivo., Conclusions: This study expands our knowledge of ubiquitomic signatures, biomarkers, and potential therapeutic targets in HCC., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background : The effect of the expression of the newly identified immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) on NK cells in core binding factor-acute myeloid leukemia (CBF-AML) remains to be investigated. Methods : Fresh bone marrow samples from a total of 39 newly diagnosed CBF-AML patients and 25 healthy donors (HDs) were collected for testing the phenotype and function state of total NK, CD56 bright , and CD56 dim NK cell subsets after in vitro stimulation. Results : The frequencies of TIGIT + cells in total NK, CD56 bright , and CD56 dim NK cell subsets had no significant difference between patients and HDs. TNF-α and INF-γ levels were uniformly lower in TIGIT + cells than the corresponding TIGIT - cells in all HDs, whereas those for TIGIT + to TIGIT - cells in patients were highly heterogenous; TIGIT expression was not related to PFP and GZMB expression in HDs, whereas it was related to higher intracellular PFP and GZMB levels in patients. Patients' TIGIT + NK cells displayed lower K562 cell-killing activity than their TIGIT - NK cells. In addition, high frequencies of TIGIT + cells in total NK and CD56 dim NK cells were associated with poor RFS. Conclusions : TIGIT expression affected the diagnostic bone marrow-sited NK cell function and had prognostic significance in CBF-AML patients.

As the world grapples with the coronavirus-19 (COVID) pandemic, more reports are coming in regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in endotheliopathy. It is a vascular condition in which endothelial cell injury or damage inflicts anatomical and functional changes in the endothelium, significantly impacting the physiological process and function. Previously, it was assumed that SARS-CoV-2 infects respiratory epithelial cells via spike glycoproteins present on the surface of the virus. However, severe cases and different autopsy studies described the clandestine role of this virus in infecting endothelial cells other than epithelial cells. It was observed that SARS-CoV-2 targets the pulmonary and extrapulmonary systems to damage the microvasculature and affect respiratory functioning, resulting in the onset of endotheliopathy, thrombosis, inflammation, pulmonary edema, and fibrosis. Such deleterious events are the consequence of the hyperactive immune response initiated by the SARS-CoV-2 infection, leading to pulmonary and extrapulmonary complications. However, the molecular mechanism behind endotheliopathy and other complications caused by this virus is elusive and will be unraveled by covering recent literature in this mini-review., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Diabetes is often associated with gastrointestinal dysfunctions, which can lead to hypoglycemia. Dexmedetomidine (DEX) is a commonly used sedative in perioperative diabetic patients and may affect gastrointestinal function., Aim: To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal dysfunction., Methods: Sedation/anesthesia scores and vital signs of streptozotocin (STZ)-induced diabetic mice under DEX sedation were observed. Diabetic mice were divided into saline and DEX groups. After injecting sedatives intraperitoneally, tight junctions (TJs) and apoptotic levels were evaluated 24 hours later to assess the intestinal barrier function. The role of DEX was validated using Villin-MMP23B flox/flox mice with intestinal epithelial deletion. In vitro , high glucose and hyperosmolarity were used to culture Caco-2 monolayer cells with STZ inter-vention. Immunofluorescence techniques were used to monitor the barrier and mitochondrial functions., Results: MMP23B protein levels in the intestinal tissue of STZ-induced diabetic mice were significantly higher than those in the intestinal tissue of control mice, with the DEX group displaying decreased MMP23B levels. Diabetes-mediated TJ dis-ruption, increased intestinal mucosal permeability, and systemic inflammation in wild-type mice might be reversed by DEX. In Caco-2 cells, MMP23B was associated with increased reactive oxygen species accumulation, mitochondrial membrane potential depolarization, and TJ disruption., Conclusion: DEX reduces MMP23B, which may potentially contribute to STZ-induced intestinal barrier dysfunction, affecting TJ modification through mitochondrial dysfunction., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Prognostic significance of soluble immune checkpoint molecule TIM-3 and its ligands in the plasma has been illustrated in various solid tumors, but such study in newly diagnosed acute myeloid leukemia (AML) remains absent. Soluble TIM-3, Gal-9 and CEACAM1 levels in the bone marrow plasma samples collected from 90 adult AML patients at diagnosis and 12 healthy donors were measured by enzyme-linked immunosorbent assays (ELISA), and 16 AML patients were simultaneously tested cell membrane TIM-3 expression by multi-color flow cytometry. AML patients had significantly elevated soluble TIM-3 levels and similar soluble Gal-9 and CEACAM1 levels compared with healthy donors (p = 0.0003, 0.26 and 0.96). In the whole cohort, high soluble TIM-3 level was the sole independent adverse prognostic factor for relapse-free survival (RFS) (p = 0.0060), and it together with adverse ELN genetic risk were independent poor prognostic factors for event-free survival (EFS) (p = 0.0030 and 0.0040); High soluble CEACAM1 level were significantly related to lower RFS (p = 0.028). In addition, high soluble Gal-9 level had significant association with lower RFS in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the first complete remission (p = 0.037). Furthermore, soluble TIM-3 level tended to have positive correlation with the percentage of non-blast myeloid TIM-3+ cells in nucleated cells in AML (r = 0.48, p = 0.073). Therefore, the high soluble TIM-3 level in the diagnostic BM plasma predicted poor outcome in adult AML patients, and high sGal-9 level was associated with relapse after allo-HSCT., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We present the synthesis, structural characterization, and reactivity studies of a tetra-zinc complex supported by the bisphenoxymethanone ligands and its transformation into various di-zinc architectures. Our findings highlight the potential of these complexes in molecular recognition, supramolecular chemistry, and catalysis., (© 2024 The Author(s). ChemPlusChem published by Wiley-VCH GmbH.)

Atherosclerosis (AS) is a major pathological basis of coronary heart disease. However, the currently available medications are unable to effectively reduce the incidence of cardiovascular events in the majority of patients with AS. Therefore, naringin has been attracting considerable attention owing to its anti-AS effects. Naringin can inhibit the growth, proliferation, invasion, and migration of vascular smooth muscle cells, ameliorate endothelial cell inflammation and apoptosis, lower blood pressure, halt the cell cycle at the G1 phase, and impede growth via its antioxidant and free radical scavenging effects. These activities suggest the potential anti-AS effects of naringin. In this review article, we comprehensively summarized the latest findings on the anti-AS effects of naringin and their underlying mechanisms, providing a crucial reference for future research on the anti-AS potential of this 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 © 2024 Lu, Li, Xu and Zhou.)

Dryocosmus kuriphilus, commonly known as the chestnut gall wasp, belongs to the family Cynipidae and is native to China. It is a highly invasive insect species causing serious damage to chestnut trees and has rapidly spread to various continents, including Europe, North America, and Oceania. The D. kuriphilus has become one of the important pests of chestnut plants in the world and is listed as a quarantine object by the European and Mediterranean Plant Protection Organization (EPPO). In this study, we used PacBio long reads, Illumina short reads, and Hi-C sequencing data to construct a chromosome-level assembly of the D. kuriphilus genome. The assembled genome includes 14,729 contigs with a total length of 2.28 Gb and a contig N50 of 0.8 Mb. With Hi-C technology, 2.17 Gb (95.02%) of contigs were anchored and oriented into the 10 pseudochromosomes with the scaffold N50 of 198.8 Mb and the scaffold N90 of 158.8 Mb. In total, 24,086 protein-coding genes were predicted in the assembled D. kuriphilus genome as the reference gene set. A total of 1.82 Gb repeats (occupying 79.7% of the genome), including 1.42 Gb of transposable elements and 0.40 Gb of tandem repeats, were identified in D. kuriphilus genome. In the evaluation of completeness, the BUSCO analysis determined a level of 98.1% completeness for the assembled genome sequences based on the Insecta database (OrthoDB version 10). The high-quality genome assembly of D. kuriphilus will not only provide a valuable reference for the study of its evolutionary history and genetic structure but also facilitate the research of host-pest interactions and invasiveness. Moreover, this genome assembly will promote in the development of effective management strategies to mitigate the economic and ecological impacts of this invasive pest on chestnut trees and ecosystems., (© 2024. The Author(s).)

The impact of respiratory diseases is vast and multifaceted, affecting individuals, healthcare systems, and global economies. In response to the spread of respiratory pathogens, masks and respirators have become pivotal, demonstrating their capability to mitigate transmission. However, the limitations of conventional face masks or respirators, such as their single-use nature, environmental impact, and the risk of contact-based transmission, have accelerated the development of antimicrobial masks. Designing effective antimicrobial masks requires a deep understanding of the properties of each layer and the identification of an optimal configuration to enhance their protective efficiency. In this study, we investigated the filtration performance, including filtration efficiency and breathability, of individual layers in conventional 3-ply masks and stacked spunbond (SB) fabrics with and without salt coating, under both dry and wet fabric conditions. We aimed to elucidate the filtration efficiency of each mask layer with respect to particle size and type (NaCl aerosols, DOP aerosols), with particular focus on the impact of salt-coated SB fabric and its application. While bare fabrics showed a decrease in filtration efficiency with increased wetness, salt-coated fabrics exhibited enhanced filtration efficiency. Importantly, evaluating the efficacy of a stack comprised of salt-coated SB fabrics across diverse antimicrobial respiratory devices highlighted its efficacy as both the outermost layer in a 3-ply mask and as a mask covering ( i.e. , a supplementary layer over a mask or respirator). This investigation not only emphasizes the significance of salt-coated antimicrobial technology in mitigating disease transmission but also offers a practical approach for adeptly implementing this technology in respiratory protection devices., Competing Interests: H.-J. C is the inventor of salt-coated fabrics and holds a patent for the technology. Nevertheless, the research presented in this study has not been documented elsewhere., (This journal is © The Royal Society of Chemistry.)

Objective: To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis (KOA), and to determine the possible mechanisms of acupotomy to alleviate cartilage degeneration., Methods: The modified Videman method was used to construct a KOA rabbit model. After modeling, 40 rabbits were randomly divided into 4 groups by a random number table: control; KOA (model); KOA + acupotomy (acupotomy), and KOA + sham acupotomy (sham), 10 in each group. After a 3-week treatment course, the knee joint activity was determined by the modified Lequesne MG index. Hematoxylin-eosin staining staining was used to examine the morphological changes of chondrocytes. Autophagy of chondrocytes was observed by transmission electron microscopy. The surface morphology of cartilage tissue was observed by scanning electron microscope. The mRNA and protein levels of AMP kinase/mammalian target of rapamycin/Unc-51 (AMPK/mTOR/ULK1) signal pathway key proteins, autophagy-related factor Beclin-1 and microtubule-associated protein 1A/1B light chain 3 (LC3) in rabbit knee cartilage were assessed by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively., Results: The modified Lequesne MG score of acupotomy group was significantly lower than that of model group (P<0.05). Pathological results showed that chondrocyte autophagy decreased and cartilage surface was rough in the model group, which recovered after acupotomy treatment. The mRNA expressions of AMPK, ULK1, Beclin-1 and the protein levels of p-AMPK, p-ULK1, Beclin-1, and LC3 II/LC3 I were decreased in the model group, while the mRNA and protein expressions of mTOR were increased (P<0.01). However, acupotomy treatment reversed these abnormal changes (P<0.05)., Conclusions: Acupotomy could effectively up-regulate the expressions of AMPK, ULK1 and Beclin1, reduce the expression of mTOR, promote autophagy, and alleviate joint degeneration. Acupotomy is a promising complementary and alternative therapy for KOA., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Due to the chemical stability of graphene, synthesis of carboxylated graphene still remains challenging during the electrochemical exfoliation of graphite. In this work, a spatially confined radical addition reaction which occurs in the sub-nanometer scaled interlayers of the expanded graphene sheets for the electrochemical synthesis of highly stable carboxylated graphene is reported. Here, formate anions act as both intercalation ions and co-reactant acid for the confinement of electro-generated carboxylic radical ( ● COOH) in the sub-nanometer scaled interlayers, which facilitates the radical addition reaction on graphene sheets. The controllable carboxylation of graphene is realized by tuning the concentration of formate anions in the electrolyte solution. The high crystallinity of the obtained product indicates the occurrence of spatially confined ● COOH addition reaction between the sub-nanometer interlayers of expanded graphite. In addition, the carboxylated graphene have been used for water desalination and hydrogen/oxygen reduction reaction. Therefore, this work provides a new method for the in situ preparation of functionalized graphene through the electrolysis and its applications in water desalination and hydrogen/oxygen reduction reactions., (© 2024 Wiley‐VCH GmbH.)

Aspergillus niger is a well-known workhorse for the industrial production of enzymes and organic acids. This fungus can also cause postharvest diseases in fruits. Although Agrobacterium tumefaciens-mediated transformation (ATMT) based on antibiotic resistance markers has been effectively exploited for inspecting functions of target genes in wild-type fungi, it still needs to be further improved in A. niger. In the present study, we re-examined the ATMT in the wild-type A. niger strains using the hygromycin resistance marker and introduced the nourseothricin resistance gene as a new selection marker for this fungus. Unexpectedly, our results revealed that the ATMT method using the resistance markers in A. niger led to numerous small colonies as false-positive transformants on transformation plates. Using the top agar overlay technique to restrict false positive colonies, a transformation efficiency of 87 ± 18 true transformants could be achieved for 10 6 conidia. With two different selection markers, we could perform both the deletion and complementation of a target gene in a single wild-type A. niger strain. Our results also indicated that two key regulatory genes (laeA and veA) of the velvet complex are required for A. niger to infect apple fruits. Notably, we demonstrated for the first time that a laeA homologous gene from the citrus postharvest pathogen Penicillium digitatum was able to restore the acidification ability and pathogenicity of the A. niger ΔlaeA mutant. The dual resistance marker ATMT system from our work represents an improved genetic tool for gene function characterization in A. niger., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: In the fight against virus-caused pandemics like COVID-19, diagnostic tests based on RT-qPCR are essential, but they are sometimes limited by their dependence on expensive, specialized equipment and skilled personnel. Consequently, an alternative nucleic acid detection technique that overcomes these restrictions, called loop-mediated isothermal amplification following reverse transcription (RT-LAMP), has been broadly investigated. Nevertheless, the developed RT-LAMP assays for SARS-CoV-2 detection still require laboratory devices and electrical power, limiting their widespread use as rapid home tests. This work developed a flexible RT-LAMP assay that gets beyond the drawbacks of the available isothermal LAMP-based SARS-CoV-2 detection, establishing a simple and effective at-home diagnostic tool for COVID-19., Methodology: A multiplex direct RT-LAMP assay, modified from the previously developed test was applied to simultaneously identify the two genes of SARS-CoV-2. We used a colorimetric readout, lyophilized reagents, and benchmarked an electro-free and micropipette-free method that enables sensitive and specific detection of SARS-CoV-2 in home settings., Results: Forty-one nasopharyngeal swab samples were tested using the developed home-testing RT-LAMP (HT-LAMP) assay, showing 100% agreement with the RT-qPCR results., Conclusions: This is the first electrically independent RT-LAMP assay successfully developed for SARS-CoV-2 detection in a home setting. Our HT-LAMP assay is thus an important development for diagnosing COVID-19 or any other infectious pandemic on a population scale., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Diem Hong Tran, Hau Thi Tran, Trang Nguyen Minh Pham, Le Minh Bui, Huong Thi Thu Phung.)

Glioblastoma represents the predominant and a highly aggressive primary neoplasm of the central nervous system that has an abnormal metabolism. Our previous study showed that chrysomycin A (Chr-A) curbed glioblastoma progression in vitro and in vivo. However, whether Chr-A could inhibit orthotopic glioblastoma and how it reshapes metabolism are still unclear. In this study, Chr-A markedly suppressed the development of intracranial U87 gliomas. The results from airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) indicated that Chr-A improved the abnormal metabolism of mice with glioblastoma. Key enzymes including glutaminase (GLS), glutamate dehydrogenases 1 (GDH1), hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD) were regulated by Chr-A. Chr-A further altered the level of nicotinamide adenine dinucleotide phosphate (NADPH), thus causing oxidative stress with the downregulation of Nrf-2 to inhibit glioblastoma. Our study offers a novel perspective for comprehending the anti-glioma mechanism of Chr-A, highlighting its potential as a promising chemotherapeutic agent for glioblastoma.

Exchange rate pass-through (ERPT) represents a degree to which changes in nominal exchange rates are transmitted into domestic prices. European Union (EU) countries have experienced the unprecedented inflationary pressure due to high geopolitical risk events. As such, understanding the ERPT plays a crucial role. This study provides a comprehensive and up-to-date analysis of ERPT to import prices for 16 EU countries from January 2006 to December 2022. Using the panel autoregressive distributed lag (ARDL) model, our findings confirm the linear, rather than nonlinear, ERPT pattern characterized by a diminishing trend over time in the EU countries. However, the degree of pass-through varies depending on country characteristics. Specifically, countries that are highly dependent on imports experience a larger ERPT. Furthermore, the degree of pass-through to import prices is more significant and persistent during periods of high uncertainty. These findings are robust across various robust analyses including sub periods. Our findings provide that help policymakers evaluate the trade-offs between exchange rate risks and macroeconomic stability during times of high uncertainty., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vo, Vu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In response to the ongoing threat posed by respiratory diseases, ensuring effective transmission protection is crucial for public health. To address the drawbacks of single-use face masks/respirators, which can be a potential source of contact-based transmission, we have designed an antimicrobial face mask and mask covering utilizing a stack of salt-coated spunbond (SB) fabric. This fabric acts as an outer layer for the face mask and as a covering over a conventional mask, respectively. We evaluated the universal antimicrobial performance of the salt-coated three-stacked SB fabric against enveloped/nonenveloped viruses and spore-forming/nonspore-forming bacteria. The distinctive pathogen inactivation efficiency was confirmed, including resistant pathogens such as human rhinovirus and Clostridium difficile . In addition, we tested other filter attributes, such as filtration efficiency and breathability, to determine the optimal layer for salt coating and its effects on performance. Our findings revealed that the outer layer of a conventional face mask plays a crucial role in contact transmission through contaminated face masks and respirators. Through contact transmission experiments using droplets involving three types of contaminants (fluorescent dyes, bacteria, and viruses), the salt-coated stacked SB fabric demonstrated a superior effect in preventing contact transmission compared to SB or meltblown polypropylene fabrics─an issue challenging to existing masks. Our results demonstrate that the use of salt-coated stacked SB fabrics as (i) the outer layer of a mask and (ii) a mask cover over a mask enhances overall filter performance against infectious droplets, achieving high pathogen inactivation and low contact-based transmission while maintaining breathability.

Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen., Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT., Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group., Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage., 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 © 2024 Wang, Wang, Su, Wang, Li, Li, Jing, Xu, Wang, Zheng, Gao, Hu, Gao and Liu.)

A new fluorescent sensor for the determination of lemon yellow was developed based on nitrogen-doped carbon quantum dots (N-CQDs), which were prepared via a hydrothermal method with dried pomelo peel and L-tyrosine. The N-CQDs exhibited the blue fluorescence with a quantum yield of 28 %. The sensing principle of N-CQDs was quenched by lemon yellow via static quenching. The potential interfering substances showed no influence on the detection of lemon yellow. The limit of detection was 0.023 mg/L and lower than that of national standard. Furthermore, the synthesized N-CQDs have been successfully applied to the measurement of lemon yellow in real samples. Hence, the N-CQDs would be a promising sensor in food analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective To identify the risk factors of patients with frequent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and construct a prediction model based on the clinical data,providing a theoretical basis for the clinical prevention and treatment. Methods A total of 25 638 COPD patients admitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic (ROC) curve. Results In the patients with frequent AECOPD,male percentage ( P <0.001),age ( P <0.001),urban residence ( P <0.001),smoking ( P <0.001),length of stay ( P <0.001),total cost ( P <0.001),antibiotic cost ( P <0.001),diabetes ( P =0.003),respiratory failure ( P <0.001),heart disease ( P <0.001),application of systemic glucocorticoids ( P <0.001),white blood cell count ( P <0.001),neutrophil percentage ( P <0.001),C-reactive protein ( P <0.001),total cholesterol ( P <0.001),and brain natriuretic peptide (BNP) ( P <0.001) were all higher than those in the patients with infrequent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabetes,heart disease, Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,respiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899 (95% CI =0.892-0.905),the sensitivity of 85.30%,and the specificity of 79.80%. Conclusion Frequent AECOPD is associated with smoking,heart disease,application of systemic glucocorticoids, Pseudomonas aeruginosa infection,age,low body mass index,and elevated BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide theoretical support for the treatment and risk factor management of the patients.