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This study investigates the metabolic responses of Auricularia cornea when cultured on de-oiled leaves of Cinnamomum longepaniculatum (DeCL), an underutilized waste product. The metabolic profiles of A. cornea cultured with four different quality ratios of DeCL substrate (0 %, 14 %, 28 % and 42 %) were analyzed by UHPLC-MS/MS-based metabolomics. A total of 516 metabolites were identified and classified into 78 categories, with phenols, alkaloids and flavonoids accounting for 26.7 % of the total. In addition, 32 metabolite biomarkers associated with eight major metabolic pathways were identified. This pioneering research provides valuable insights into the utilization of DeCL, and expands our knowledge of the metabolic dynamics underlying the growth of A. cornea on alternative substrates., 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.)

This study explored the structure and performance of starch-based antibacterial films reinforced with black tea cellulose nanocrystals (BT-CNCs). The optimal addition amount of BT-CNCs is 5 % (w/w Starch). This nanocrystal-infused film, incorporating chitosan (CS), ε-polylysine (ε-PL), and zinc oxide nanoparticles (ZnONP) as antibacterial agents, exhibited a smooth, continuous surface. The addition of BT-CNCs and antibacterial agents did not change the group characteristic peaks of the film, but changed the crystallinity slightly. The films, namely St, St/CNCs, St/CNCs/CS, and St/CNCs/ε-P, maintained high light transmittance (above 80 %), except for the St/CNCs/ZnONP film, which effectively shielded UV radiation. The combined use of antibacterial agents and BT-CNCs enhanced the water and oxygen barrier properties of the film. Notably, the St/CNCs/CS film exhibited the lowest solubility (17.74 % ± 0.36) and the highest tensile strength (14.23 ± 0.16 MPa). The antibacterial efficacy of the films decreased in the order of St/CNCs/ZnONP, St/CNCs/ε-PL, and St/CNCs/CS, with a more pronounced inhibitory effect on E. coli compared to S. aureus. This study marries natural waste recycling with cutting-edge food packaging technology, setting a new benchmark for the development of sustainable packaging materials., 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.)

Ion transport is a critical phenomenon underpinning numerous biological, physical, and chemical systems. Proton transistors leveraging proton transport face significant limitations, such as a low on-off ratio and deficient carrier mobility, which restrict their applicability in biological and other scenarios. This study explores the use of two-dimensional (2D) vacancy-residing transition metal phosphorus trichallcogenide-based membranes as the active layer for proton field-effect transistors. The synthesized Cd 0.85 PS 3 Li 0.15 H 0.15 membrane exhibits a well-organized layered structure and high hydrophilicity, with nanometer-sized interlayers containing interconnected water networks. These distinct features facilitate proton conduction, leading to a high proton conductivity value of 0.83 S cm -1 at 98% relative humidity and 90 °C, with an activation energy of 0.26 eV. The Cd 0.85 PS 3 Li 0.15 H 0.15 -based proton transistor demonstrates tunability via gate voltage, thereby enabling effective modulation of proton flow across source and drain electrodes. The transistor notably showcases superior switching characteristics, with an on/off ratio surpassing 5.51 and a carrier mobility of 8.84 × 10 -2 cm 2 V -1 s -1 . The underlying mechanism for this performance enhancement is attributed to electric-field-induced switching in Cd vacancies. This research boosts the development of highly versatile ionotropic devices by introducing advanced 2D ion-conductive membranes.

Background and Purpose: Prostate cancer remains a major public health burden worldwide. Polo like kinase 4 (PLK4) has emerged as a promising therapeutic target in prostate cancer due to its key roles in cell cycle regulation and tumour progression. This study aims to develop and characterize the novel curcumin analogue NL13 as a potential therapeutic agent and PLK4 inhibitor against prostate cancer., Experimental Approach: NL13 was synthesized and its effects were evaluated in prostate cancer cells and mouse xenograft models. Kinome screening and molecular modelling identified PLK4 as the primary target. Antiproliferative and proapoptotic mechanisms were explored via cell cycle, apoptosis, gene and protein analyses., Key Results: Compared with curcumin, NL13 exhibited much greater potency in inhibiting PC3 (IC 50 , 3.51 μM vs. 35.45 μM) and DU145 (IC 50 , 2.53 μM vs. 29.35 μM) prostate cancer cells viability and PLK4 kinase activity (2.32 μM vs. 246.88 μM). NL13 induced G2/M cell cycle arrest through CCNB1/CDK1 down-regulation and triggered apoptosis via caspase-9/caspase-3 cleavage. These effects were mediated by PLK4 inhibition, which led to the inactivation of the AKT signalling pathway. In mice, NL13 significantly inhibited tumour growth and modulated molecular markers consistent with in vitro findings, including decreased p-AKT and increased cleaved caspase-9/3., Conclusion and Implications: NL13, a novel PLK4-targeted curcumin analogue, exerts promising anticancer properties against prostate cancer by disrupting the PLK4-AKT-CCNB1/CDK1 and apoptosis pathways. NL13 represents a promising new agent for prostate cancer therapy., (© 2024 British Pharmacological Society.)

The tumor stroma plays a crucial role in tumor progression, and the interactions between the extracellular matrix, tumor cells, and stromal cells collectively influence tumor progression and the efficacy of therapeutic agents. Currently, utilizing components of the tumor stroma for drug delivery is a noteworthy strategy. A number of targeted drug delivery systems designed based on tumor stromal components are entering clinical trials. Therefore, this paper provides a thorough examination of the function of tumor stroma in the advancement of targeted drug delivery systems. One approach is to use tumor stromal components for targeted drug delivery, which includes certain stromal components possessing inherent targeting capabilities like HA, laminin, along with targeting stromal cells homologously. Another method entails directly focusing on tumor stromal components to reshape the tumor stroma and facilitate drug delivery. These drug delivery systems exhibit great potential in more effective cancer therapy strategies, such as precise targeting, enhanced penetration, improved safety profile, and biocompatibility. Ultimately, the deployment of these drug delivery systems can deepen our comprehension of tumor stroma and the advanced development of corresponding drug delivery systems., 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. Published by Elsevier B.V.)

Light exposure significantly impacted the coloration and metabolism of Auricularia cornea, although the underlying mechanisms remain unclear. This study aimed to test the apparent color and pigment metabolic profiles of A. cornea in response to red (λp = 630 nm) and blue (λp = 463 nm) visible light exposure. Colorimeter analysis showed that fruiting bodies appeared bright-white under red-light and deeper-red under blue-light, both with a yellow tinge. On the 40th day of light-exposure, bodies were collected for metabolite detection. A total of 481 metabolites were targeted analysis, resulting in 18 carotenoids and 11 anthocyanins. Under red and blue light exposure, the total carotenoids levels were 1.1652 μg/g and 1.1576 μg/g, the total anthocyanins levels were 0.0799 μg/g and 0.1286 μg/g, respectively. Four differential metabolites and three putative gene linked to the visual coloration of A. cornea were identified. This pioneering study provides new insights into the role of light in regulating A. cornea pigmentation and metabolic profile., Competing Interests: Declaration of Competing Interest 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 Elsevier B.V. All rights reserved.)

All-solid-state lithium-sulfur batteries (ASSLSBs) have attracted intense interest due to their high theoretical energy density and intrinsic safety. However, constructing durable lithium (Li) metal anodes with high cycling efficiency in ASSLSBs remains challenging due to poor interface stability. Here, a compositionally stable, self-lithiated tin (Sn)-carbon (C) composite interlayer (LSCI) between Li anode and solid-state electrolyte (SSE), capable of homogenizing Li-ion transport across the interlayer, mitigating decomposition of SSE, and enhancing electrochemical/structural stability of interface, is developed for ASSLSBs. The LSCI-mediated Li metal anode enables stable Li plating/stripping over 7000 h without Li dendrite penetration. The ASSLSBs equipped with LSCI thus exhibit excellent cycling stability of over 300 cycles (capacity retention of ≈80%) under low applied pressure (<8 MPa) and demonstrate improved rate capability even at 3C. The enhanced electrochemical performance and corresponding insights of the designed LSCI broaden the spectrum of advanced interlayers for interface manipulation, advancing the practical application of ASSLSBs., (© 2024 Wiley‐VCH GmbH.)

Purpose: To evaluate the diagnostic performance of image-based artificial intelligence (AI) studies in predicting muscle-invasive bladder cancer (MIBC). (2) To assess the reporting quality and methodological quality of these studies by Checklist for Artificial Intelligence in Medical Imaging (CLAIM), Radiomics Quality Score (RQS), and Prediction model Risk of Bias Assessment Tool (PROBAST)., Materials and Methods: We searched Medline, Embase, Web of Science, and The Cochrane Library databases up to October 30, 2023. The eligible studies were evaluated using CLAIM, RQS, and PROBAST. Pooled sensitivity, specificity, and the diagnostic performances of these models for MIBC were also calculated., Results: Twenty-one studies containing 4256 patients were included, of which 17 studies were employed for the quantitative statistical analysis. The CLAIM study adherence rate ranged from 52.5% to 75%, with a median of 64.1%. The RQS points of each study ranged from 2.78% to 50% points, with a median of 30.56% points. All models were rated as high overall ROB. The pooled area under the curve was 0.85 (95% confidence interval (CI) 0.81-0.88) for computed tomography, 0.92 (95% CI 0.89-0.94) for MRI, 0.89 (95% CI 0.86-0.92) for radiomics and 0.91 (95% CI 0.88-0.93) for deep learning, respectively., Conclusion: Although AI-powered muscle-invasive bladder cancer-predictive models showed promising performance in the meta-analysis, the reporting quality and the methodological quality were generally low, with a high risk of bias., Critical Relevance Statement: Artificial intelligence might improve the management of patients with bladder cancer. Multiple models for muscle-invasive bladder cancer prediction were developed. Quality assessment is needed to promote clinical application., Key Points: Image-based artificial intelligence models could aid in the identification of muscle-invasive bladder cancer. Current studies had low reporting quality, low methodological quality, and a high risk of bias. Future studies could focus on larger sample sizes and more transparent reporting of pathological evaluation, model explanation, and failure and sensitivity analyses., (© 2024. The Author(s).)

Lithium (Li) metal batteries are deemed as promising next-generation power solutions but are hindered by the uncontrolled dendrite growth and infinite volume change of Li anodes. The extensively studied 3D scaffolds as solutions generally lead to undesired "top-growth" of Li due to their high electrical conductivity and the lack of ion-transporting pathways. Here, by reducing electrical conductivity and increasing the ionic conductivity of the scaffold, the deposition spot of Li to the bottom of the scaffold can be regulated, thus resulting in a safe bottom-up plating mode of the Li and dendrite-free Li deposition. The resulting symmetrical cells with these scaffolds, despite with a limited pre-plated Li capacity of 5 mAh cm -2 , exhibit ultra-stable Li plating/stripping for over 1 year (11 000 h) at a high current density of 3 mA cm -2 and a high areal capacity of 3 mAh cm -2 . Moreover, the full cells with these scaffolds further demonstrate high cycling stability under challenging conditions, including high cathode loading of 21.6 mg cm -2 , low negative-to-positive ratio of 1.6, and limited electrolyte-to-capacity ratio of 4.2 g Ah -1 ., (© 2024 Wiley‐VCH GmbH.)

A strained triple nanohoop with a shared central benzene unit is synthesized using a threefold intramolecular ring-closing approach. Among the five possible constitutional isomers, the isomer with the highest D 3h symmetry is isolated, the structure of which contains three nanohoop blades and a central hexaphenylbenzene unit. The structure is elucidated using NMR spectroscopy and mass spectrometry. The optical and electrochemical properties are investigated, revealing a moderate fluorescence quantum yield of 40 %. A water-soluble nanomaterial is prepared using a nanoparticle encapsulation method, and a fluorescence quantum yield of 10 % is retained, which demonstrates the potential of the nanomaterial in biological systems., (© 2024 Wiley-VCH GmbH.)

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis targeting chimeras (PROTACs) emerge as a promising approach to overcome the limitations of FLT3 inhibitors, while the development of orally bioavailable FLT3-PROTACs faces great challenges. Here, we report the rational design and evaluation of a series of Gilteritinib-based FLT3-PROTACs. Among them, B3-2 exhibited the strongest antiproliferative activity against FLT3-ITD mutant AML cells, and significantly induced FLT3-ITD protein degradation. Mechanistic investigations demonstrated that B3-2 induced FLT3-ITD degradation in a ubiquitin-proteasome-dependent manner. More importantly, B3-2 exhibited an oral bioavailability of 5.65%, and oral administration of B3-2 showed good antitumor activity in MV-4-11 xenograft models. Furthermore, B3-2 showed strong antiproliferative activity against FLT3 resistant mutations, highlighting its potential in overcoming drug resistance., 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.)

The scraps produced while processing packaging materials will cause a waste of resources. In this study, starch-based self-reinforced film (SSRF) using thermoplastic starch (TPS, 45 wt%) and polypropylene (PP, 53 wt%) was developed. The effect of extrusion times (1-4 times) on the film structure and performance was explored. The results show as the number of extrusions increases, the color of SSRF deepens from gray-white to brown, and the crystallinity increases. The mechanical properties of the four types of SSRF first increase and then decrease. The 2-SSRF has the best performance, with tensile strength of 13.23 MPa, elongation at break of 61.35%, Young's modulus of 1128.99 MPa, and flexural strength of 33.19 MPa. Proper extrusion improves the compatibility of TPS and PP. However, repeated extrusion will cause PP degradation and TPS carbonization, reducing interfacial interaction. This study developed new starch-based self-reinforced film and provided theoretical guidance for reusing packaging material scraps., 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.)

Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. Anti-human epidermal growth factor receptor 2 (HER2) therapy has demonstrated its promising effects on HER2-positive USC. However, data on prognostic relevance and immune microenvironment are limited in HER2-positive USC. This study aimed to determine the clinicopathologic features, prognosis, and the immune microenvironment trait in HER2 status in USC. We applied immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and multi-color immunofluorescence to investigate HER2 expression and amplification, PD-L1 expression, and tumor infiltration lymphocytes (TIL) in 77 USC (61 pure and 16 mixed-type USC). HER2 IHC 1 + , 2 + , and 3 + were found in 26, 18, and 10 USC, respectively. HER2 staining frequently had an incomplete membrane (basolateral or "U"-shaped) pattern. Twenty-three cases (23/54, 42.6%) showed an intra-tumor heterogeneous staining. HER2 amplification was present in 16/77 (20.8%) USC. HER2 amplification was significantly associated with deep myometrial invasion (> 1/2), and increased intra-epithelial and stromal density of CD20 + or CD8 + TIL (all P < 0.05), but not with USC subtypes (pure versus mixed-type), PD-L1 expression, CD4 + TIL, CD68 + histiocytes, or the CD4 + /CD8 + ratio (p > 0.05). HER2 amplification was associated with poor overall and progression-free survival in USC, but lost the prognostic significance on multivariate analysis. We concluded that HER2 amplified USC had adverse clinical outcomes, but showed the potential active immune microenvironment. Our findings raised the possibility of the combined anti-HER2 and immunotherapy for HER2-positive USC in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Aim: To explore and describe workplace stress levels and health-promoting behaviours reported by emergency nurses in China, and to investigate factors associated with workplace stress and health-promoting lifestyle behaviours among emergency nurses., Methods: A cross-sectional study was conducted between October 2019 and January 2020. Nurses (n = 1565) were recruited from the emergency departments of 54 hospitals within the Sichuan Province of West China. Each subject completed the Chinese versions of the Nurse Workplace Stress Scale, the Health-Promoting Lifestyle Profile (HPLP-II) and demographic questions. Linear regression analyses were used to identify associations between workplace stress and the health-promoting lifestyle and risk factors correlated with these two measurements., Results: Workplace stress was negatively associated with health-promoting behaviours. Linear regression analysis showed that gender, marital status, whether wages met expected standards and professional rank were found to be associated with health promotion behaviours; marital status, whether income met expected standards, the number of night shifts per month and health promotion behaviours were found to be associated with workplace stress., Conclusion: Higher levels of workplace stress are associated with lower levels of engagement in health-promoting behaviours, suggesting the potential for reducing workplace stress through the adoption of healthier habits. Policies should prioritize workplace stress by promoting healthy lifestyle initiatives., (© 2024 John Wiley & Sons Australia, Ltd.)

Implantable neural devices that record neurons in various states, including static states, light activities such as walking, and vigorous activities such as running, offer opportunities for understanding brain functions and dysfunctions. However, recording neurons under vigorous activities remains a long-standing challenge because it leads to intense brain deformation. Thus, three key requirements are needed simultaneously for neural devices, that is, low modulus, low specific interfacial impedance, and high electrical conductivity, to realize stable device/brain interfaces and high-quality transmission of neural signals. However, they always contradict each other in current material strategies. Here, a soft fiber neural device capable of stably tracking individual neurons in the deep brain of medium-sized animals under vigorous activity is reported. Inspired by the axon architecture, this fiber neural device is constructed with a conductive gel fiber possessing a network-in-liquid structure using conjugated polymers and liquid matrices and then insulated with soft fluorine rubber. This strategy reconciles the contradictions and simultaneously confers the fiber neural device with low modulus (300 kPa), low specific impedance (579 kΩ µm 2 ), and high electrical conductivity (32 700 S m -1 ) - ≈1-3 times higher than hydrogels. Stable single-unit spike tracking in running cats, which promises new opportunities for neuroscience is demonstrated., (© 2024 Wiley‐VCH GmbH.)

A pioneering pink cultivar of Auricularia cornea, first commercially cultivated in 2022, lacks genomic data, hindering research in genetic breeding, gene discovery, and product development. Here, we report the de novo assembly of the pink A. cornea Fen-A1 genome and provide a detailed functional annotation. The genome is 73.17 Mb in size, contains 86 scaffolds (N50 ∼ 5.49 Mb), 59.09% GC content and encodes 19,120 predicted genes with a BUSCO completeness of 92.60%. Comparative genomic analysis reveals the phylogenetic relatedness of Fen-A1 and remarkable gene family dynamics. Putative genes were found mapped to 3 antibiotic-related, 36 light-dependent and 25 terpene metabolites. In addition, 789 CAZymes genes were classified, revealing the dynamics of quality loss due to postharvest refrigeration. Overall, our work is the first report on a pink A. cornea genome and provides a comprehensive insight into its complex functions., Competing Interests: Declaration of competing interest 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. Published by Elsevier Inc.)

Hibiscus mutabilis L. is a Traditional Chinese Medicinal plant of significant value. However, there has been limited research focusing specifically on its flowers. In this study, we report the isolation of one novel and nine known flavonoids from the flowers of H. mutabilis L. The structures of these compounds were elucidated using chemical and comprehensive spectral analysis, involving 1D, 2D NMR, and HRESIMS. The novel compound was further evaluated for its anti-inflammatory and cytotoxic activities using in vitro assays on RAW264.7 cells. Compound 1 at the concentration of 6.25 μM significantly inhibited the production of NO and TNF-α induced by LPS in RAW264.7 cells, exhibiting superior efficacy compared to the positive control dexamethasone, thus indicating its potential as an anti-inflammatory drug candidate.

Auricularia cornea has garnered attention due to its nutrition, culinary applications, and promising commercial prospects. However, there is little information available regarding the metabolic profiling of various colors strains. In this study, 642 metabolites across 64 classes were identified by LC-MS/MS to understand the metabolic variations between white, pink and dark brown strains. Notably, prenol lipids, carboxylic acids and fatty acyls accounted for 46.8 % of the total. Comparative analysis revealed 17 shared differential metabolites (DMs) among them. ACP vs ACW exhibited 17 unique metabolites, including d-arginine and maleic acid, etc. ACP vs ACB showed 5 unique metabolites, with only PS(18:1(9Z)/0:0) demonstrating up-regulation. ACB vs ACW showed 8 unique metabolites, including 4-hydroxymandelic acid and 5'-methylthioadenosine, etc. KEGG enrichment analysis highlighted pathway variations, and MetPA analysis identified key-pathways influencing DMs accumulation in A. cornea. This pioneering metabolomics study offers insights into A. cornea metabolic profiling, potential applications, and guides further research., 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.)

Background: In a phase 3 trial, bulevirtide monotherapy led to a virologic response in patients with chronic hepatitis D. Pegylated interferon (peginterferon) alfa-2a is recommended by guidelines as an off-label treatment for this disease. The role of combination therapy with bulevirtide and peginterferon alfa-2a, particularly with regard to finite treatment, is unclear., Methods: In this phase 2b, open-label trial, we randomly assigned patients to receive peginterferon alfa-2a alone (180 μg per week) for 48 weeks; bulevirtide at a daily dose of 2 mg or 10 mg plus peginterferon alfa-2a (180 μg per week) for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks; or bulevirtide at a daily dose of 10 mg alone for 96 weeks. All the patients were followed for 48 weeks after the end of treatment. The primary end point was an undetectable level of hepatitis D virus (HDV) RNA at 24 weeks after the end of treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group., Results: A total of 24 patients received peginterferon alfa-2a alone, 50 received 2 mg and 50 received 10 mg of bulevirtide plus peginterferon alfa-2a, and 50 received 10 mg of bulevirtide monotherapy. At 24 weeks after the end of treatment, HDV RNA was undetectable in 17% of the patients in the peginterferon alfa-2a group, in 32% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15 to 50; P<0.001). At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% of the patients in the peginterferon alfa-2a group, in 26% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. The most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia. The majority of adverse events were of grade 1 or 2 in severity., Conclusions: The combination of 10-mg bulevirtide plus peginterferon alfa-2a was superior to bulevirtide monotherapy with regard to an undetectable HDV RNA level at 24 weeks after the end of treatment. (Funded by Gilead Sciences; MYR 204 ClinicalTrials.gov number, NCT03852433.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Congenital sideroblastic anemia (CSA) is a rare and heterogeneous group of genetic disorders. Conventional treatment include pyridoxine (vitamin B6) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can alleviate anemia in the majority of cases. Nevertheless, some CSA cases remain unresponsive to pyridoxine or are unable to undergo allo-HSCT. Novel management approaches is necessary to be developed. To explore the response of luspatercept in treating congenital sideroblastic anemia., Case Summary: We share our experience in luspatercept in a 4-year-old male patient with CSA. Luspatercept was administered subcutaneously at doses of 1.0 mg/kg/dose to 1.25 mg/kg/dose every 3 wk, three consecutive doses, evaluating the hematological response. Luspatercept leading to a significant improvement in the patient's anemia. The median hemoglobin during the overall treatment with three doses of luspatercept was 90 (75-101) g/L, the median absolute reticulocyte count was 0.0593 (0.0277-0.1030) × 10 12 /L, the median serum ferritin was 304.3 (234.4-399) ng/mL, and the median lifespan of mature red blood cells was 80 (57-92) days. Notably, no adverse reactions, such as headaches, dizziness, vomiting, joint pain, or back pain, were observed during the treatment period., Conclusion: We believe that luspatercept might emerge as a viable therapeutic option for the maintenance treatment of CSA or as a bridging treatment option before hematopoietic stem cell transplantation., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Glioblastoma (GBM) is one of the most aggressive brain tumors and often leads to poor outcomes. Studies have indicated that glycan levels are significantly correlated with the pathogenesis and development of cancers. However, whether glycan levels can serve as diagnostic or prognostic biomarkers in GBM remains unclear., Methods: We obtained glycomic profiles in tissue and serum samples from 55 individuals with GBM using a well-established lectin biochip platform probing with 11 specific lectins., Results: Our univariate analysis showed that 5 out of the 11 lectin-probed glycans (LPGs) were significantly higher in GBM tissues than in peri-tumoral tissues. After logistic regression analyses, only the Jacalin-probed T-antigen difference between the two groups remained significant (p = 0.037). Moreover, survival-related analyses showed that the level of Jacalin-probed T-antigen was significantly associated with the progression-free survival (p = 0.038) of patients. However, none of the LPG levels were correlated with the overall survival or the chemosensitivity to temozolomide therapy. The correlation coefficient analysis showed a moderate-to-strong correlation in the Jacalin-probed T-antigen levels between GBM tissues and serum samples, indicating its potential usefulness as a non-invasive GBM progression biomarker., Interpretation: Glycomics analyses can be helpful in the prediction of GBM recurrences and may provide information useful for GBM glycan-based target therapies or vaccine development., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Atherosclerosis is one of the major causes of death worldwide, and it is closely related to many cardiovascular diseases, such as stroke, myocardial infraction and angina. Although traditional surgical and pharmacological interventions can effectively retard or slow down the progression of atherosclerosis, it is very difficult to prevent or even reverse this disease. In recent years, with the rapid development of nanotechnology, various nanoagents have been designed and applied to different diseases including atherosclerosis. The unique atherosclerotic microenvironment with signature biological components allows nanoplatforms to distinguish atherosclerotic lesions from normal tissue and to approach plaques specifically. Based on the process of atherosclerotic plaque formation, this review summarises the nanodrug delivery strategies for atherosclerotic therapy, trying to provide help for researchers to understand the existing atherosclerosis management approaches as well as challenges and to reasonably design anti-atherosclerotic nanoplatforms.

Background: Conventional five-port laparoscopic surgery, the current standard treatment for colorectal carcinoma (CRC), has many disadvantages., Aim: To assess the influence of reduced-port laparoscopic surgery (RPLS) on perioperative indicators, postoperative recovery, and serum inflammation indexes in patients with CRC., Methods: The study included 115 patients with CRC admitted between December 2019 and May 2023, 52 of whom underwent conventional five-port laparoscopic surgery (control group) and 63 of whom underwent RPLS (research group). Comparative analyses were performed on the following dimensions: Perioperative indicators [operation time (OT), incision length, intraoperative blood loss (IBL), and rate of conversion to laparotomy], postoperative recovery (first postoperative exhaust, bowel movement and oral food intake, and bowel sound recovery time), serum inflammation indexes [high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], postoperative complications (anastomotic leakage, incisional infection, bleeding, ileus), and therapeutic efficacy., Results: The two groups had comparable OTs and IBL volumes. However, the research group had a smaller incision length; lower rates of conversion to laparotomy and postoperative total complication; and shorter time of first postoperative exhaust, bowel movement, oral food intake, and bowel sound recovery; all of which were significant. Furthermore, hs-CRP, IL-6, and TNF-α levels in the research group were significantly lower than the baseline and those of the control group, and the total effective rate was higher., Conclusion: RPLS exhibited significant therapeutic efficacy in CRC, resulting in a shorter incision length and a lower conversion rate to laparotomy, while also promoting postoperative recovery, effectively inhibiting the inflammatory response, and reducing the risk of postoperative complications., Competing Interests: Conflict-of-interest statement: Dr. Cao has nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The prognostic significance of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains controversial. Notably, there is evidence suggesting an association between tissue stiffness and the aggressiveness of the disease. We therefore aimed to explore the effect of tissue stiffness on LNM-related invasiveness in PTC patients., Method: A total of 2492 PTC patients from 3 hospitals were divided into an LNM group and a non-LNM group based on their pathological results. The effects of interior lesion stiffness (E) and peri-cancerous tissue stiffness (Eshell) on the LNM-related recurrence rate and mortality in each patient with PTC subgroup were analyzed. The activation of cancer-associated fibroblasts (CAFs) and extracellular matrix component type 1 collagen (COL-I) in the lesion were compared and analyzed across different subgroups. The underlying biological basis of differences in each subgroup was identified using RNA sequencing (RNA-seq) data., Results: The Eshell value and Eshell/E in the LNM group were significantly higher than those in the non-LNM group of patients with PTC (Eshell: 72.72 ± 5.63 vs 66.05 ± 4.46; Eshell/E: 1.20 ± 1.72 vs 1.09 ± 1.10, P < .001). When Eshell/E > 1.412 and LNM were both present, the recurrence rate and mortality were significantly increased compared to those of group of patients with LNM (91.67% and 7.29%, respectively). The CAF activation and COL-I content in the Eshell/E+ group were significantly higher than those in the Eshell/E- group (all P < .001), and the RNA-seq results revealed significant extracellular matrix (ECM) remodeling in the LNM-Eshell/E+ group., Conclusions: Stiff peri-cancerous tissue induced CAF activation, COL-I deposition, and ECM remodeling, resulting in a poor prognosis for PTC patients with LNM., (© The Author(s) 2024. Published by Oxford University Press.)

T. panzhihuanense and T. latisporum are white truffle species native to China, of which T. panzhihuanense has significant commercial potential, with high nutritional value and unique flavor. Maturity is an important factor affecting the nutrition and aroma of truffles, which determines their economic status. Here, a label-free-based comparative proteomics method was used to determine the proteomic profiles of T. panzhihuanense and T. latisporum at two different stages of maturity. The results showed that both maturity and species significantly affected the protein expression patterns. T. panzhihuanense responded stronger to maturity than T. latisporum, accompanied by a more complex interaction network between proteins. Some critical proteins were regulated by maturity and variety, including those involved in aroma formation, e.g., S-adenosyl-methionine synthetase. The enrichment of oxidation-reduction processes, glycolysis, and SNARE interactions in vesicular transport were driven by species and maturity. This study provides the first insights into the proteomic profiles of T. panzhihuanense and T. latisporum, revealing the roles of key proteins and biological processes in their maturation., 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.)

To explore the influence of comfort nursing theory on the postoperative rehabilitation quality of patients with intracranial aneurysms. From October 2017 to December 2022, 315 patients with intracranial aneurysms underwent interventional surgery in our hospital were included in this retrospective study and divided into the routine group (n = 105) and comfort nursing group (n = 210) based on different nursing methods. The Glasgow Outcome Scale (GOS) was used to assess patient rehabilitation outcomes. Patients' anxiety, pain, quality of life, and their satisfaction with treatment were compared. Compared with the patients receiving routine nursing, the time for comfortable nursing patients to resume normal diet, get out of bed and exercise, and the total hospital stay were significantly shortened. And the GOS score of patients receiving comfort nursing was significantly higher than that of patients receiving routine nursing. After nursing, self-rating anxiety scale and visual analog scale scores of comfortable nursing patients were significantly lower than those of routine nursing, and Karnofsky performance status scores were significantly higher than those of routine nursing. This showed that receiving comfortable nursing was beneficial to improve perioperative anxiety and depression in patients with intracranial aneurysm, and significantly improve the quality of life of patients. The total satisfaction of comfortable nursing patients was 95.24%, while that of routine nursing patients was 76.19%. Complications occurred in 30 patients receiving routine nursing, while only 15 patients received comfort nursing. The immune indexes such as CD3+, CD4+, and CD23+ of comfortable nursing patients were significantly higher than the routine nursing patients within 1 and 5 days after operation, while the immune indexes of CD8+ were lower than the routine nursing patients 5 days after operation. Comfortable nursing from the perspective of quality nursing can significantly improve the physiological indicators of patients with intracranial aneurysms, accelerate the progress of postoperative rehabilitation, improve the anxiety, pain and quality of life of patients, and improve the satisfaction of patients with nursing. Comfort nursing from the perspective of quality nursing can reduce the occurrence of postoperative complications, which may be achieved by improving the patient's immune function., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The TOR1B gene is known to play a pivotal role in maintaining cellular homeostasis and responding to endoplasmic reticulum stress. However, its involvement in cancer remains relatively understudied. This study seeks to explore the prognostic implications of TOR1B across various cancers, with a specific focus on Basal-like Breast Cancer (BLBC) and its underlying cellular mechanisms. Through comprehensive analysis of data from TCGA, TARGET, GEO, and GTEx, we investigated TOR1B expression and its correlation with patient outcomes. Furthermore, in vitro experiments conducted on BLBC cell lines examined the impact of TOR1B modulation on cell viability, apoptosis, and metabolic activity under varying oxygen levels. Our statistical analysis encompassed differential expression analysis, survival analysis, and multivariate Cox regression. Our findings indicate that TOR1B is overexpressed in BLBC and other cancers, consistently correlating with poorer prognosis. Elevated TOR1B levels were significantly associated with reduced overall and disease-free survival in BLBC patients. In vitro experiments further revealed that TOR1B knockdown augmented apoptosis and influenced metabolic activity, particularly under hypoxic conditions, highlighting its potential role in cancer cell adaptation to stress. Overall, our study underscores the importance of TOR1B in cancer progression, particularly in BLBC, where it serves as a notable prognostic indicator. The interaction between TOR1B and metabolic pathways, as well as its regulation by HIF-1α, suggests its significance in adapting to hypoxia, thereby positioning TOR1B as a promising therapeutic target for aggressive breast cancer subtypes., (© 2024. The Author(s).)

The photoexcited dissolved organic matter (DOM) could produce reactive intermediates, affecting chemical oxidant transformation in UV based advanced oxidation processes (AOPs). This study confirmed the critical role of triplet state DOM ( 3 DOM*), generated from DOM photoexcitation, in the transformation of monochloramine (NH 2 Cl), a commonly used chemical oxidant and disinfectant in water treatment. NH 2 Cl (42.25 μM, as Cl 2 ) was decayed by 17.4-73.4 % within 60 min, primarily due to 3 DOM* , in DOM (2-30 mg C L -1 ) solutions irradiated by 365 nm, where NH 2 Cl has no absorption. The second-order quenching rate constants of triplet state model photosensitizers by NH 2 Cl were determined to be 0.95(± 0.04)-4.49(± 0.04)× 10 8 M -1 s -1 by using laser flash photolysis. As a reductant, 3 DOM* reacted with NH 2 Cl through one-transfer mechanism, leading to amino radical (NH 2 • ) generation, which then transferred to ammonia (NH 4 + , pKa 9.25) through H-abstraction by the phenolic moieties in DOM. Additionally, the intermediate product of 3 DOM* oxidized by NH 2 Cl or those triplet state quinones can hydrolyze to form phenolic moieties, elevating NH 4 + yield to higher than 99% upon 365 nm irradiation. These findings suggest that the widespread DOM can be applied to convert NH 2 Cl via 3 DOM* with minimal toxic risks., 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.)

Neural stem cells (NSCs) transplantation is an attractive and promising treatment strategy for spinal cord injury (SCI). Various pathological processes including the severe inflammatory cascade and difficulty in stable proliferation and differentiation of NSCs limit its application and translation. Here, a novel physico-chemical bifunctional neural stem cells delivery system containing magnetic nanoparticles (MNPs and methylprednisolone (MP) is designed to repair SCI, the former regulates NSCs differentiation through magnetic mechanical stimulation in the chronic phase, while the latter alleviates inflammatory response in the acute phase. The delivery system releases MP to promote microglial M2 polarization, inhibit M1 polarization, and reduce neuronal apoptosis. Meanwhile, NSCs tend to differentiate into functional neurons with magnetic mechanical stimulation generated by MNPs in the static magnetic field, which is related to the activation of the PI3K/AKT/mTOR pathway. SCI mice achieve better functional recovery after receiving NSCs transplantation via physico-chemical bifunctional delivery system, which has milder inflammation, higher number of M2 microglia, more functional neurons, and axonal regeneration. Together, this bifunctional NSCs delivery system combined physical mechanical stimulation and chemical drug therapy is demonstrated to be effective, which provides new treatment insights into clinical transformation of SCI repair., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Cytology and high-risk human papilloma virus (hrHPV) cotesting is the mainstay in the detection of cervical carcinoma., Methods: Endocervical adenocarcinoma (EAC) is divided into HPV-associated adenocarcinoma (HPVA) and HPV-independent adenocarcinoma (HPVI) by the World Health Organization classification (2020). The detection effect of cotesting is suggested to be different among EAC subtypes and precursors, but has not well-documented yet. In this study, the authors retrospectively analyzed cotesting among adenocarcinoma in situ (AIS), HPVA, and HPVI. The cohort included 569 AIS and 498 EAC consisting of 371 (74.5%) HPVA, 111 (22.3%) HPVI, and 16 (3.2%) adenocarcinoma, not otherwise specified., Results: The authors found that AIS patients were significantly younger than HPVA and HPVI (mean ± SD, years: 40.7 ± 8.6; HPVA, 44.8 ± 9.3; HPVI, 50.0 ± 11.3; p < .001) and had a higher prevalence of concurrent squamous intraepithelial lesions (75.5%, HPVA, 37.2%; HPVI, 12.6%; p < .001). The detection rate of hrHPV test or cytology was substantially higher in AIS and HPVA than in HPVI (97.7% and 90.2% vs. 16.5%, p < .001, or 71.1% and 71.9% vs. 60.7%, p = .042, respectively). Cytology and hrHPV cotesting was superior to a single test in the detection of EAC and AIS. The detection rate of cotesting amounted to 100% in AIS and 94.3% in HPVA but was substantially lower in HPVI (72.2%) (p < .001)., Conclusions: The authors conclude that cytology and hrHPV cotesting can maximize the detection effect for HPVA and AIS but is not optimal for HPVI., (© 2024 American Cancer Society.)

Aims: Synaptic dysfunction is a hallmark pathology of Alzheimer's disease (AD) and is strongly associated with cognitive impairment. Abnormal phagocytosis by the microglia is one of the main causes of synapse loss in AD. Previous studies have shown that the absence of melanoma 2 (AIM2) inflammasome activity is increased in the hippocampus of APP/PS1 mice, but the role of AIM2 in AD remains unclear., Methods: Injection of Aβ 1-42 into the bilateral hippocampal CA1 was used to mimic an AD mouse model (AD mice). C57BL/6 mice injected with AIM2 overexpression lentivirus and conditional knockout of microglial AIM2 mice were used to confirm the function of AIM2 in AD. Cognitive functions were assessed with novel object recognition and Morris water maze tests. The protein and mRNA expression levels were evaluated by western blotting, immunofluorescence staining, and qRT-PCR. Synaptic structure and function were detected by Golgi staining and electrophysiology., Results: The expression level of AIM2 was increased in AD mice, and overexpression of AIM2 induced synaptic and cognitive impairments in C57BL/6 mice, similar to AD mice. Elevated expression levels of AIM2 occurred in microglia in AD mice. Conditional knockout of microglial AIM2 rescued cognitive and synaptic dysfunction in AD mice. Excessive microglial phagocytosis activity of synapses was decreased after knockout of microglial AIM2, which was associated with inhibiting complement activation., Conclusion: Our results demonstrated that microglial AIM2 plays a critical role in regulating synaptic plasticity and memory deficits associated with AD, providing a new direction for developing novel preventative and therapeutic interventions for this disease., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

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.

In this study, cellulose was extracted from black tea residues to produce black tea cellulose nanocrystals (BT-CNCs) using an optimized acid hydrolysis method. The structure and performance of BT-CNCs were evaluated. The results showed that the optimal conditions for acidolysis of BT-CNCs included a sulfuric acid concentration of 64 %, a solid-liquid ratio of 1:18 (w/v), a hydrolysis temperature of 45 °C, and a hydrolysis time of 50 min. The optimization process resulted in a 44.8 % increase in the yield of BT-CNCs, which exhibited a crystallinity of 68.57 % and were characterized by the typical cellulose I structure. The diameters of the particles range from 5 to 45 nm, and they exhibit aggregation behavior. Notably, BT-CNCs demonstrated excellent storage stability, and the Tyndall effect occurred when exposed to a single beam of light. Although the thermal stability of BT-CNCs decreased, their primary thermal degradation temperature remained above 200 °C. The colloidal nature of BT-CNCs was identified as a non-Newtonian fluid with "shear thinning" behavior. This study introduces a novel method to convert tea waste into BT-CNCs, increasing the yield of BT-CNCs and enhancing waste utilization. BT-CNCs hold promise for application in reinforced composites, offering substantial industrial value., 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.)

This review explores the growing interest in 2D layered materials, such as graphene, h-BN, transition metal dichalcogenides (TMDs), and black phosphorus (BP), with a specific focus on recent advances in strain engineering. Both experimental and theoretical results are delved into, highlighting the potential of strain to modulate physical properties, thereby enhancing device performance. Various strain engineering methods are summarized, and the impact of strain on the electrical, optical, magnetic, thermal, and valleytronic properties of 2D materials is thoroughly examined. Finally, the review concludes by addressing potential applications and challenges in utilizing strain engineering for functional devices, offering valuable insights for further research and applications in optoelectronics, thermionics, and spintronics., (© 2024 Wiley‐VCH GmbH.)

Background: Radiologists currently accept the concept of "interfascial plane (IFP)" to understand retroperitoneal anatomy, replacing Meyers' classic tricompartmental theory. Despite much research on retroperitoneal anatomy, its anatomical structure, embryonic origin and developmental process still require further exploration to guide the optimization of surgical process. This study aims to explore the anatomical basis of IFP related to laparoscopic upper retroperitoneal surgery (LURS) and to compare the clinical outcomes of trans-interfascial plane procedures for LURS (TIFP-LURS) with conventional LURS (Con-LURS)., Methods: The study consisted of two parts: cadaveric and clinical study. The cadaveric study involved dissecting and observing the retroperitoneal fasciae and IFP in 32 cadavers using gross anatomical and histological methods. This retrospective clinical study compared the perioperative data and complications of 229 patients who underwent TIFP-LURS and 121 patients who underwent Con-LURS for upper retroperitoneal lesions at our center., Results: The cadaveric study revealed that the retroperitoneal space was composed of multilaminar fasciae that formed potential bloodless spaces among them, that could be used as surgical landmarks and operating planes. The clinical study showed that TIFP-LURS had a significantly less estimated blood loss, lower intraoperative complication rate, lower postoperative complication rate, shorter hospital-stay and lower long-term postoperative complications rate than Con-LURS. Multivariate analysis indicated that the TIFP procedure was an independent protective factor for decreasing the risk of postoperative complications., Conclusions: The IFP are potential avascular spaces that can be used during laparoscopic surgery, and TIFP-LURS is a novel surgical approach that can improve the safety and efficacy of laparoscopic surgery for upper retroperitoneal lesions., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-632/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

The COVID-19 pandemic has made assessing vaccine efficacy more challenging. Besides neutralizing antibody assays, systems vaccinology studies use omics technology to reveal immune response mechanisms and identify gene signatures in human peripheral blood mononuclear cells (PBMCs). However, due to their low proportion in PBMCs, profiling the immune response signatures of dendritic cells (DCs) is difficult. Here, we develop a predictive model for evaluating early immune responses in dendritic cells. We establish a THP-1-derived dendritic cell (TDDC) model and stimulate their maturation in vitro with an optimal dose of attenuated yellow fever 17D (YF-17D). Transcriptomic analysis reveals that type I interferon (IFN-I)-induced immunity plays a key role in dendritic cells. IFN-I regulatory biomarkers (IRF7, SIGLEC1) and IFN-I-inducible biomarkers (IFI27, IFI44, IFIT1, IFIT3, ISG15, MX1, OAS2, OAS3) are identified and validated in vitro and in vivo. Furthermore, we apply this TDDC approach to various types of vaccines, providing novel insights into their early immune response signatures and their heterogeneity in vaccine recipients. Our findings suggest that a standardizable TDDC model is a promising predictive approach to assessing early immunity in DCs. Further research into vaccine efficacy assessment approaches on various types of immune cells could lead to a systemic regimen for vaccine development in the future.

Dual-modifications of jet milling and hydroxypropylation were used to improve the functional properties of maize starch (HM, containing 67 % amylose). The fractions obtained in three sizes (HM-S, HM-M, HM-L) were further treated with 10 % and 30 % propylene oxide (PO10 and PO30). The infrared peak of starch at 2794 cm -1 indicated the successful introduction of hydroxypropyl groups. The molar degree of substitution (MS) increased with the degree of jet milling. The MS of HM-L-PO10 is 0.4, that of HM-M-PO10 is 0.7, and that of HM-S-PO10 is 0.9. The crystallinity of dual-modified HM increased, but the crystal type remained unchanged, still being B-type. Dual-modification significantly improved the performance of starch, and the higher the degree of modification, the better the optimization effect. The lowest enthalpy changes of gelatinization (ΔH = 3.49 J/g), the best freeze-thaw stability, the highest elongation at break (110.42 %) and transmittance (81.22 %) were shown in HM-S-PO30. The present study confirms that HM-S-PO30 films have the best physicochemical and mechanical properties, which provide new insights into optimizing starch-based packaging materials., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Drug-resistant juvenile myoclonic epilepsy (DR-JME) remains a significant challenge in neurology. Traditional management strategies often fail to achieve satisfactory control, necessitating innovative treatments., Objective: This case report aims to evaluate the efficacy and safety of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN-DBS) in a patient with DR-JME., Methods: We describe the treatment of a patient with DR-JME using STN-DBS. The patient underwent implantation and received high-frequency stimulation (HFS) at the STN., Results: One year post-implantation, the patient demonstrated a substantial reduction in motor seizure frequency by 87.5%, with improvements in quality of life and seizure severity by 52.0% and 46.7%, respectively. No adverse events were reported during the follow-up period., Conclusions: This case represents the first report of favorable outcomes with STN-DBS in a patient with DR-JME, suggesting that long-term HFS of the STN may be a promising treatment option for patients suffering from this condition., (© 2024. Fondazione Società Italiana di Neurologia.)

Efficient obstacle-avoidance path planning is critical for orchards with numerous irregular obstacles. This paper presents a continuous bidirectional Quick-RRT* (CBQ-RRT*) algorithm based on the bidirectional RRT (Bi-RRT) and Quick-RRT* algorithms and proposes an expansion cost function that evaluates path smoothness and length to overcome the limitations of the Quick-RRT* algorithm for non-holonomic mobile robot applications. To improve the zigzag between dual trees caused by the dual-tree expansion of the Bi-RRT algorithm, CBQ-RRT* proposes the CreateConnectNode optimization method, which effectively solves the path smoothness problem at the junction of dual trees. Simulations conducted on the ROS platform showed that the CBQ-RRT* outperformed the unidirectional Quick-RRT* in terms of efficiency for various orchard layouts and terrain conditions. Compared to Bi-RRT*, CBQ-RRT* reduced the average path length and maximum heading angle by 8.5% and 21.7%, respectively. In addition, field tests confirmed the superior performance of the CBQ-RRT*, as evidenced by an average maximum path lateral error of 0.334 m, a significant improvement over Bi-RRT* and Quick-RRT*. These improvements demonstrate the effectiveness of the CBQ-RRT* in complex orchard environments., 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 Ye, Li and Li.)

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader A20 with excellent pharmacokinetic properties was discovered through reasonable design. A20 selectively inhibited the proliferation of FLT3-ITD mutant acute myeloid leukemia (AML) cells and potently induced FLT3-ITD degradation through the ubiquitin-proteasome system. Notably, oral administration of A20 resulted in complete tumor regression on subcutaneous AML xenograft models. Furthermore, on systemic AML xenograft models, A20 could completely eliminate the CD45 + CD33 + human leukemic cells in murine and significantly prolonged the survival time of mice. Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.

Deoxynivalenol (DON) is a common food contaminant that can impair male reproductive function. This study investigated the effects and mechanisms of DON exposure on progenitor Leydig cell (PLC) development in prepubertal male rats. Rats were orally administrated DON (0-4 mg/kg) from postnatal days 21-28. DON increased PLC proliferation but inhibited PLC maturation and function, including reducing testosterone levels and downregulating biomarkers like HSD11B1 and INSL3 at ≥2 mg/kg. DON also stimulated mitochondrial fission via upregulating DRP1 and FIS1 protein levels and increased oxidative stress by reducing antioxidant capacity (including NRF2, SOD1, SOD2, and CAT) in PLCs in vivo. In vitro, DON (2-4 μM) inhibited PLC androgen biosynthesis, increased reactive oxygen species production and protein levels of DRP1, FIS1, MFF, and pAMPK, decreased mitochondrial membrane potential and MFN1 protein levels, and caused mitochondrial fragmentation. The mitochondrial fission inhibitor mdivi-1 attenuated DON-induced impairments in PLCs. DON inhibited PLC steroidogenesis, increased oxidative stress, perturbed mitochondrial homeostasis, and impaired maturation. In conclusion, DON disrupts PLC development in prepubertal rats by stimulating mitochondrial fission.

Background: Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies., Objective: We aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC., Methods: In vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing., Results: PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed CTNNB1 somatic alterations were only found in responders (3/5) while ZNRF3 alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst CYP27A1 and ABCA1 expression were positively correlated to in vitro mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs., Conclusion: ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. CYP27A1 and ABCA1 expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation., 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 Zhang, Wu, Su, Liu, Jiang, Jiang, Wu, Chen, Li, Zheng, Sun, Peng, Han, Ning, Ye and Wang.)

Memristor possesses great potential and advantages in neuromorphic computing, while consistency and power consumption issues have been hindering its commercialization. Low cost and accuracy are the advantages of human brain, so memristors can be used to construct brain-like synaptic devices to solve these problems. In this work, a five-layer AlO x device with a V-shaped oxygen distribution is used to simulate biological synapses. The device simulates synapse structurally. Further, under electrical stimulation, O 2- moves to the Ti electrode and oxygen vacancy (V o ) moves to the Pt electrode, thus forming a conductive filament (CF), which simulates the Ca 2+ flow and releases neurotransmitters to the postsynaptic membrane, thus realizing the transmission of information. By controlling applied voltage, the regulation of Ca 2+ gated pathway is realized to control the Ca 2+ internal flow and achieve different degrees of information transmission. Long-term Potentiation (LTP)/Long-term Depression (LTD), Spike Timing Dependent Plasticity (STDP), these basic synaptic performances can be simulated. The AlO x device realizes low power consumption (56.7 pJ/392 fJ), high switching speed (25 ns/60 ns), and by adjusting the window value, the nonlinearity is improved (0.133/0.084), a high recognition accuracy (98.18%) is obtained in neuromorphic simulation. It shows a great prospect in multi-value storage and neuromorphic computing., (© 2024 Wiley‐VCH GmbH.)

Replacement of liquid electrolytes with polymer gel electrolytes is recognized as a general and effective way of solving safety problems and achieving high flexibility in wearable batteries 1-6 . However, the poor interface between polymer gel electrolyte and electrode, caused by insufficient wetting, produces much poorer electrochemical properties, especially during the deformation of the battery 7-9 . Here we report a strategy for designing channel structures in electrodes to incorporate polymer gel electrolytes and to form intimate and stable interfaces for high-performance wearable batteries. As a demonstration, multiple electrode fibres were rotated together to form aligned channels, while the surface of each electrode fibre was designed with networked channels. The monomer solution was effectively infiltrated first along the aligned channels and then into the networked channels. The monomers were then polymerized to produce a gel electrolyte and form intimate and stable interfaces with the electrodes. The resulting fibre lithium-ion battery (FLB) showed high electrochemical performances (for example, an energy density of about 128 Wh kg -1 ). This strategy also enabled the production of FLBs with a high rate of 3,600 m h -1 per winding unit. The continuous FLBs were woven into a 50 cm × 30 cm textile to provide an output capacity of 2,975 mAh. The FLB textiles worked safely under extreme conditions, such as temperatures of -40 °C and 80 °C and a vacuum of -0.08 MPa. The FLBs show promise for applications in firefighting and space exploration., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this study, starch-based biodegradable composites (SDC) were prepared by extruding using thermoplastic starch (TPS, 65%wt), polylactic acid (PLA, 30%wt) and poly (butylene adipate co-terephthalate) (PBAT, 5%wt). Structure and properties of the SDC were compared by performing 1-, 2-, 3-times extrusion. The results show that in-situ re-extrusion refines the TPS in composites and reduces the size of the phase. As the number of extrusions increases, the ester bond of composites at 868 cm -1 disappears, the crystallinity increases, and the thermal stability decreases. Among the three types of composites, the mechanical properties and hydrophobic properties of the material obtained by the 2-times are the most outstanding. Compared with SDC, the elongation at break and Young's modulus of SDC-2 are significantly increased, with an increase of 8.01 % and 1.28 % in the machine direction and an increase of 11.02 % and 1.79 % in the transverse direction respectively. Additionally, water contact angle range of SDC-2 from 98.7° to 101.7°. Therefore, SDC prepared by 2-times in-situ re-extrusion has the best film properties and is an ideal packaging material. This study presents a novel method for fabricating starch-degradable composite films by in-situ re-extrusion, providing new insights into the development of starch packaging materials., 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.)

Acute myocardial infarction (AMI) represents the leading cause of cardiovascular death worldwide, and it is thus pivotal to develop effective approaches for the timely detection of AMI markers, especially possessing the characteristics of antibody-free, signal amplification, and manipulation convenience. We herein construct a MoS 2 nanosheet-powered CRISPR/Cas12a sensing strategy for sensitive determination of miR-499, a superior AMI biomarker to protein markers. The presence of miR-499 at a trace level is able to induce a significantly enhanced fluorescence signal in a DNA-based molecular engineering platform, which consists of CRISPR/Cas12a enzymatic reactions and MoS 2 nanosheet-controllable signal reporting components. The MoS 2 nanosheets were characterized by using atomic force microscopy (AFM) and transmission electron microscope (TEM). The detection feasibility was verified by using polyacrylamide gel electrophoresis (PAGE) analysis and fluorescence measurements. The detection limit is determined as 381.78 pM with the linear range from 0.1 ⅹ 10 -9 to 13.33 ⅹ 10 -9  M in a fast manner (about 30 min). Furthermore, miRNA detection in real human serum is also conducted with desirable recovery rates (89.5 %-97.6 %), which may find potential application for the clinic diagnosis. We describe herein the first example of MoS 2 nanosheet-based signal amplified fluorescence sensor for effective detection of AMI-related miRNA., 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.)

The olympicenyl radical (OR) has long been a fascinating spin doublet hydrocarbon radical that evoked theoretical and experimental research interests, but the chemistry of olympicenyl was limited by its inherent instability. Recently, this field was revived by the advent of stable, multi-substituted ORs and the isolation of them in the crystalline phase. In this minireview, we summarize the early studies on the pristine OR, as well as the recent advances on the substituted OR derivatives, heteroatom-containing OR derivatives, and OR-based diradicals and polyradicals. The synthetic chemistry, stabilization strategies, self-association behaviors, reactivities, and applications in the biological field of the abovementioned compounds were discussed., (© 2023 Wiley-VCH GmbH.)

Per- and polyfluoroalkyl substances (PFAS) are widely used synthetic chemicals that persist in the environment and bioaccumulate in animals and humans. There is growing evidence that PFAS exposure adversely impacts neurodevelopment and neurological health. Steroid 5α-reductase 1 (SRD5A1) plays a key role in neurosteroidogenesis by catalyzing the conversion of testosterone or pregnenolone to neuroactive steroids, which influence neural development, cognition, mood, and behavior. This study investigated the inhibitory strength and binding interactions of 18 PFAS on human and rat SRD5A1 activity using enzyme assays, molecular docking, and structure-activity relationship analysis. Results revealed that C9-C14 PFAS carboxylic acid at 100 μM significantly inhibited human SRD5A1, with IC 50 values ranged from 10.99 μM (C11) to 105.01 μM (C14), and only one PFAS sulfonic acid (C8S) significantly inhibited human SRD5A1 activity, with IC 50 value of 8.15 μM. For rat SRD5A1, C9-C14 PFAS inhibited rat SRD5A1, showing the similar trend, depending on carbon number of the carbon chain. PFAS inhibit human and rat SRD5A1 in a carbon chain length-dependent manner, with optimal inhibition around C11. Kinetic studies indicated PFAS acted through mixed inhibition. Molecular docking revealed PFAS bind to the domain between NADPH and testosterone binding site of both SRD5A1 enzymes. Inhibitory potency correlated with physicochemical properties like carbon number of the carbon chain. These findings suggest PFAS may disrupt neurosteroid synthesis and provide insight into structure-based inhibition of SRD5A1., Competing Interests: Declaration of competing interest The authors have no conflict of interest to be disclosed., (Copyright © 2024. Published by Elsevier B.V.)

A cubic DNA nanocage probe is able to enter EVs derived from MDA-MB-231 cells and react with miRNA-10b. The probe-loaded EVs were employed to monitor the process of entry of miRNA-10b into MCF-10A cells, allowing visualization of EV-mediated intercellular communication of miRNA-10b between the cancer cells.