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A pair of unidentified atropisomeric dimers, penicisteckins G (1) and H (2), and twelve known compounds (3-16) were isolated from the marine coral-derived fungus Penicillium steckii SCISO41228. Their structures including the absolute configuration were determined by HR-ESI-MS, ECD, 1D-, and 2D-NMR spectra. Compounds 1 and 2 exhibited potent antibacterial activity against most pathogenic strains, especially for MASA and Micrococcus luteus, with MIC values of 4.0 μg·mL-1. In addition, compounds 2 and 3 exhibit potent antioxidant activity with IC50 values of 10.76 and 8.66 μg·mL-1, respectively., (© 2024 Wiley‐VCH GmbH.)

Pancreatic ductal adenocarcinoma (PDAC) resists conventional chemo/radiation and immunotherapy. In PDAC, oncogenic KRAS (KRAS*) drives glycolysis in cancer cells to consume available glucose and produce abundant lactate, creating profound immune suppression in the tumor microenvironment. Here, we combined KRAS* inhibition with agents targeting the major arms of the immunity cycle: CXCR1/2 inhibitor for myeloid cells, antagonistic anti-LAG3 antibody for T cells, and agonistic anti-41BB antibody for dendritic cells. This combination elicited robust anti-tumor regression in iKPC mice bearing large autochthonous tumors. While untreated mice succumbed within 3 weeks, sustained treatment led to durable complete tumor regression and prolonged survival in 36% of mice at 6 months. Mechanistic analyses revealed enhanced T cell infiltration and activation, depletion of immunosuppressive myeloid cells, and increased antigen cross-presentation by dendritic cells within the tumor core. These findings highlight the promise of KRAS* inhibitors alongside immunotherapy as a potential PDAC treatment avenue, warranting clinical investigation.

Terpestacin (1), fusaproliferin (2), and their derivatives are a class of sesterterpenes featured by a trans-fused 5/15-membered ring skeleton. There are 45 natural products (1, 2, 4-27, 65-83) isolated from various wild fungi (Fusarium sp., Bipolaris sorokiniana, Arthrinium sp., etc.) or from genetic mutants via biosynthetic gene clusters mining, and 37 derivatives (28-64) produced by semi-synthetic modifications. These compounds show a diverse range of important bioactivities such as antivirus, antimicrobial, cytotoxic, phytotoxic, anti-flammatory, and brine shrimp lethal activities. To date, two racemic and five enantioselective chemical total syntheses of 1 (including 2 and their isomers) have been developed. Over the past decade, a number of biosynthetic gene clusters or their mutants, along with their encoding enzymes responsible for producing sesterterpenes such as terpestacin and its derivatives, have also been identified. This review covers the literature from the year 1993, when 1 was firstly discovered, to May 2024, focusing on the bioactivities and syntheses of 1 and its derivatives or isomers., (© 2024 Wiley‐VCH GmbH.)

Marine microbial secondary metabolites with diversified structures have been found as promising sources of anti-inflammatory lead compounds. This review summarizes the sources, chemical structures, and pharmacological properties of anti-inflammatory natural products reported from marine microorganisms in the past three years (2021-2023). Approximately 252 anti-inflammatory compounds, including 129 new ones, were predominantly obtained from marine fungi and they are structurally divided into polyketides (51.2%), terpenoids (21.0%), alkaloids (18.7%), amides or peptides (4.8%), and steroids (4.3%). This review will shed light on the development of marine microbial secondary metabolites as potential anti-inflammatory lead compounds with promising clinical applications in human health.

Macrolactins have attracted considerable attention due to their value and application in medicine and agriculture. However, poor yields severely hinder their broader application in these fields. This study aimed to improve macrolactins production in Bacillus siamensis using a combined atmospheric and room-temperature plasma mutagenesis and a microbial microdroplet culture system. After 25 days of treatment, a desirable strain with macrolactins production 3.0-fold higher than that of the parental strain was successfully selected. The addition of 30 mg/L ZnSO 4 further increased macrolactins production to 503 ± 37.6 μg/mL, representing a 30.9 % improvement in production compared to controls. Based on transcriptome analysis, the synthesis pathways of amino acids, fengycin, and surfactin were found to be downregulated in IMD4036. Further fermentation experiments confirmed that inhibition of the comparative fengycin synthesis pathway was potentially driving the increased production of macrolactins. The strategies and possible mechanisms detailed in this study can provide insight into enhancing the production of other secondary metabolites toxic to the producer strains., 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.)

One new quinazoline-containing diketopiperazine (1), along with 24 known compounds including nine alkaloids (2-9, and 25), thirteen lactones (10-22), aspterric acid (23), and catechol (24), were isolated from the marine sponge-derived Penicillium sp. SCSIO41043. Their planar structures were unequivocally elucidated by spectroscopic analysis. The absolute configuration of 1 was determined by a comparison of reported and experimental electronic circular dichroism (ECD) spectra. Compound 16 was found to notably inhibit the growth of five pathogenic bacteria and fungi with MIC values ranging from 0.5-16.0 μg/mL. Compounds 7, 17, 20, and 22 demonstrated moderate activity against Micrococcus luteus with MIC values ranging from 35.6 to 71.1 μg/mL. Moreover, 1-3 displayed different degrees of antioxidant activity with EC50 values of 0.98, 0.60, 0.46 mg/mL, respectively., (© 2024 Wiley‐VCH GmbH.)

What Is Already Known About This Topic?: The syndromic surveillance system, exemplified by the influenza-like illness (ILI) surveillance system, has long been crucial in providing early warnings of influenza epidemics., What Is Added by This Report?: The analysis revealed that employing reported influenza case data from the nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS) enhanced the early detection of influenza epidemics, particularly within the context of multiple respiratory pathogens circulating concurrently., What Are the Implications for Public Health Practice?: The NIDRIS, characterized by its extensive coverage, obligatory reporting, high specificity, and real-time data transmission, offers a valuable tool for the effective early detection of influenza epidemics. Utilizing this system could enhance preparedness and responses to such health crises, potentially mitigating their impact on public health., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Background: The PANoptosis pathway is a recently identified mechanism of cellular death that involves the interaction and synchronization among cellular pyroptosis, apoptosis, and necrosis. More and more evidence suggests that PANoptosis is involved in the development and treatment of cancer. However, a comprehensive understanding of the influence of PANoptosis genes on prognostic value, tumor microenvironment characteristics, and therapeutic outcomes in patients with ovarian cancer (OC) remains incomplete., Objective: The present work was designed to devise a PANoptosis signature for OC prognosis and explore its potential molecular function., Methods: For this study, we obtained RNA sequencing and clinical data for ovarian cancer from the Cancer Genome Atlas (TCGA) and the GSE32062 cohort. Somatic variants of PANoptosis-related genes (PRGs) in OC were analyzed using GSCA. TCGA-OC and GSE32062 were used to construct training and validation cohorts for the model. Differential expression and correlation analyses were performed following the screening of genes with prognostic ability using univariate Cox analysis. Least Absolute Shrinkage nd Selection Operator (LASSO) regression was performed to construct PRG signature based on genes that were differentially expressed and correlated with prognosis. CIBER-SORT and ESTIMATE were used to analyze the relationship between the PRGs signature and immune infiltration. TIDE was used to analyze the relationship between the PRG signature and immune checkpoint genes. OncoPredict was used to analyze the relationship between the PRG signature and the drug sensitivity. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of PRGs in OC., Results: The PRG signature was constructed using three prognostic genes (AIM2, APAF1, and ZBP1) in both TCGA-OC. The results showed that the PRGs signature had an AUC of 0.521, 0.546, and 0.598 in TCGA-OC and 0.620, 0.586, and 0.579 in GSE32062 to predict to predict OS at 1-, 3-, and 5-year intervals. Furthermore, a higher PRG signature risk score was significantly associated with shorter OS (HR = 1.693, 95% CI: 1.303 - 2.202, p = 8.34 × 10^-5 in TCGA-OC and HR = 1.63, 95% CI: 1.13 - 2.35, p = 0.009 in GSE32062). The risk score was identified as the independent prognostic factor for OC. Patients categorized according to their risk score exhibited notable variations in immune status, response to immunotherapy, and sensitivity to drugs. AIM2, APAF1, and ZBP1 were significantly aberrantly expressed in OC cell lines., Conclusion: The PRG signature has the potential to serve as a prognostic predictor for OC and to provide new insights into OC treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A dimeric citrinin derivative with a unique spiro[chroman-2,3'-isochroman] skeleton, xerucitrinic acid C (1), and a new citrinin derivative, cladosporin E (6), along with ten known polyketides (2-5 and 7-12), were isolated from the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41428. Their structures were elucidated through comprehensive spectral data analysis. The absolute configurations of 1 and 6 were determined by quantum chemical calculations. Compound 1 exhibited significant inhibitory effects on Staphylococcus aureus and Streptococcus suis, with the MIC of 25 μg/mL for both bacterial strains. Xerucitrinin C (3) exhibited significant radical scavenging activity against DPPH, with an IC50 value of 25.4 μM, and also demonstrated inhibitory activity against phosphodiesterase-4 (PDE4). Moreover, cladosporin C (7) notably inhibited prostate cancer cells PC-3 and 22Rv1, with IC50 values of 6.10 and 9.25 μM, respectively., (© 2024 Wiley‐VCH GmbH.)

Marine-derived fungi are assuming an increasingly central role in the search for natural leading compounds with unique chemical structures and diverse pharmacological properties. However, some gene clusters are not expressed under laboratory conditions. In this study, we have found that a marine-derived fungus Aspergillus sp. SYPUF29 would survive well by adding an exogenous nitric oxide donor (sodium nitroprusside, SNP) and nitric oxide synthetase inhibitor (L-NG-nitroarginine methyl ester, L-NAME) in culture conditions. Moreover, using the LC-MS/MS, we initially assessed and characterized the difference in metabolites of Aspergillus sp. SYPUF29 with or without an additional source of nitrogen. We have found that the metabolic pathway of Arginine and proline metabolism pathways was highly enriched, which was conducive to the accumulation of alkaloids and nitrogen-containing compounds after adding an additional source of nitrogen in the cultivated condition. Additionally, the in vitro anti-neuroinflammatory study showed that the extracts after SNP and L-NAME were administrated can potently inhibit LPS-induced NO-releasing of BV2 cells with lower IC 50 value than without nitric oxide. Further Western blotting assays have demonstrated that the mechanism of these extracts was associated with the TLR4 signaling pathway. Additionally, the chemical investigation was conducted and led to nine compounds ( SF1 - SF9 ) from AS1; and six of them belonged to alkaloids and nitrogen-containing compounds ( SF1 - SF6 ), of which SF1 , SF2 , and SF8 exhibited stronger activities than the positive control, and showed potential to develop the inhibitors of neuroinflammation.

Four new sesquiterpenoids, talaroterpenes A-D ( 1 - 4 ), were isolated from the mangrove-derived fungus Talaromyces sp. SCSIO 41412. The structures of compounds 1 - 4 were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of 1 - 4 were assigned based on single-crystal X-ray diffraction and calculated electronic circular dichroism analysis. Talaroterpenes A-D ( 1 - 4 ) were evaluated with their regulatory activities on nuclear receptors in HepG2 cells. Under the concentrations of 200 μM, 1 , 3 and 4 exhibited varying degrees of activation on ABCA1 and PPARα , while 4 showed the strongest activities. Furthermore, 4 induced significant alterations in the expression of downstream target genes CLOCK and BMAL1 of RORα, and the in silico molecular docking analysis supported the direct binding interactions of 4 with RORα protein. This study revealed that talaroterpene D ( 4 ) was a new potential non-toxic modulator of nuclear receptors.

Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I ( 1 ), and one new phloroglucinol derivative, speradine J ( 8 ), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro .

Two new C 23 -steroids derivatives, cyclocitrinoic acid A ( 1 ) and cyclocitrinoic acid B ( 2 ), and a new isocoumarin metabolite, (3 R ,4 S )-6,8-dihydroxy-3,4,5-trimethyl-7-carboxamidelisocoumarin ( 10 ), together with 12 known compounds ( 3 - 9 , 11 - 15 ) were isolated from the mangrove-sediment fungus Penicillium sp. SCSIO 41429. The structures of the new compounds were comprehensively characterized by 1D and 2D NMR, HRESIMS and ECD calculation. All isolates were evaluated for pancreatic lipase (PL) inhibitory and antioxidant activities. The biological evaluation results revealed that compounds 2 , 14 and 15 displayed weak or moderate inhibition against PL, with IC 50 values of 32.77, 5.15 and 2.42 µM, respectively. In addition, compounds 7 , 12 and 13 showed radical scavenging activities against DPPH, with IC 50 values of 64.70, 48.13, and 75.54 µM, respectively. In addition, molecular docking results indicated that these compounds had potential for PL inhibitory and antioxidant activities, which provided screening candidates for antioxidants and a reduction in obesity.

Three new polyketides, including three ester derivatives ( 1 , 3 , and 5 ) and a new natural product, which was a benzoquinone derivative, embelin A ( 4 ), together with nine known ones ( 2 and 6 - 13 ), were isolated from the mangrove-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by detailed NMR and MS spectroscopic analyses. The X-ray single-crystal diffraction analysis of 4 was described for the first time. Compound 9 displayed obvious inhibition against PDE4 with an inhibitory ratio of 40.78% at 10 μM. Compound 12 showed DPPH radical scavenging activity, with an EC 50 of 16.21 µg/mL, compared to the positive control (ascorbic acid, EC 50 , 11.22 µg/mL). Furthermore, compound 4 exhibited cytotoxicity against PC-3 and LNCaP with IC 50 values of 18.69 and 31.62 µM, respectively.

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new ( 1 and 2 ) and four known ( 3 - 6 ) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis . Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster ( alt ) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH 3 to a carboxyl group to produce 4 from 3 . Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1 , 2 , 5 , and 6 from 4 . Alternapyrone G ( 1 ) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aβ treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.

Avicennia marina (Forssk.) Vierh. is a highly salt-tolerant mangrove, and its fruit has been traditionally used for treating constipation and dysentery. In this study, a pectin (AMFPs-0-1) was extracted and isolated from this fruit for the first time, its structure was analyzed, and the effects on the human gut microbiota were investigated. The results indicated that AMFPs-0-1 with a molecular weight of 798 kDa had a backbone consisting of alternating →2)-α-L-Rhap-(1→ and →4)-α-D-GalpA-(1→ residues and side chains composed of →3-α-L-Araf-(1→-linked arabinan with a terminal β-L-Araf, →5-α-L-Araf-(1→-linked arabinan, and →4)-β-D-Galp-(1→-linked galactan that linked to the C-4 positions of all α-L-Rhap residues in the backbone. It belongs to a type I rhamnogalacturonan (RG-I) pectin but has no arabinogalactosyl chains. AMFPs-0-1 could be consumed by human gut microbiota and increase the abundance of some beneficial bacteria, such as Bifidobacterium, Mitsuokella, and Megasphaera, which could help fight digestive disorders. These findings provide a structural basis for the potential application of A. marina fruit RG-I pectic polysaccharides in improving human intestinal health., 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.)

Four new compounds, including one drimane sesquiterpene lactone (1), one isocoumarin (2), one coumarin (3), and a new natural product (4), as well as fourteen known compounds were obtained from a deep-sea derived Cladosporium sp. SCSIO 41318. The structures of the new compounds were determined using extensive NMR and HRESIMS spectroscopic analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction measurements. Biological assays showed that compounds (1, 6, 7, 9-12, 14, 15, 17, 18) exhibited varying degrees of antimicrobial activity against the tested human pathogenic bacteria and plant pathogenic fungi. Besides, penicitrinone A (11) and penicitrinol A (12) displayed weak antitumor activities against the 22Rv1 cell line., (© 2024 Wiley‐VCH GmbH.)

Temporal lobe epilepsy (TLE) stands as the predominant adult focal epilepsy syndrome, characterized by dysfunctional intrinsic brain dynamics. However, the precise mechanisms underlying seizures in these patients remain elusive. Our study encompassed 116 TLE patients compared with 51 healthy controls. Employing microstate analysis, we assessed brain dynamic disparities between TLE patients and healthy controls, as well as between drug-resistant epilepsy (DRE) and drug-sensitive epilepsy (DSE) patients. We constructed dynamic functional connectivity networks based on microstates and quantified their spatial and temporal variability. Utilizing these brain network features, we developed machine learning models to discriminate between TLE patients and healthy controls, and between DRE and DSE patients. Temporal dynamics in TLE patients exhibited significant acceleration compared to healthy controls, along with heightened synchronization and instability in brain networks. Moreover, DRE patients displayed notably lower spatial variability in certain parts of microstate B, E and F dynamic functional connectivity networks, while temporal variability in certain parts of microstate E and G dynamic functional connectivity networks was markedly higher in DRE patients compared to DSE patients. The machine learning model based on these spatiotemporal metrics effectively differentiated TLE patients from healthy controls and discerned DRE from DSE patients. The accelerated microstate dynamics and disrupted microstate sequences observed in TLE patients mirror highly unstable intrinsic brain dynamics, potentially underlying abnormal discharges. Additionally, the presence of highly synchronized and unstable activities in brain networks of DRE patients signifies the establishment of stable epileptogenic networks, contributing to the poor responsiveness to antiseizure medications. The model based on spatiotemporal metrics demonstrated robust predictive performance, accurately distinguishing both TLE patients from healthy controls and DRE patients from DSE patients., Competing Interests: Declaration of competing interest The authors report no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to provide physicians with insights into the clinical manifestations and outcomes of children and young adolescents experiencing sleep terrors following SARS-CoV-2 infection., Methods: We enrolled patients who developed new onset sleep terrors after SARS-CoV-2infection fromDecember2022to April 2023 in the Xijing hospital, Xi'an, China., Results: We enrolled six patients who experienced sleep terrors following SARS-CoV-2 infection. Out of these patients, five were children and only one was an adolescent, with a mean age of 9 years. Neuroimaging results were negative for all cases. Sleep terrors occurred during both the active course of COVID-19 illness and the recovery period in all patients. Symptoms included crying or screaming in terror, hyperactivity, inappropriate behavior and periods of mental confusion during sleep. These episodes typically occurred 40 min to 1 h after falling asleep. EEG monitoring confirmed two patients' episodes occurred during non-rapid eye movement (NREM) stage 3 sleep. The duration of sleep terrors ranged from 3mines to30 mines, with each patient experiencing 3-4 to 30-40 instances. Initially, the frequency of episodes was highest at 3-4 times per night, gradually decreasing to once a night, then once a week, until complete disappearance. No medical intervention was required. Clinical follow-up ranged from 6 to 12 months, with spontaneous remission occurring within 1 week to 2 months for different patients., Conclusion: SARS-CoV-2 infection may precipitate acute sleep terrors in children and adolescents. The course of these sleep terrors is generally benign, with all patients achieving spontaneous complete remission over time., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: Epilepsy and migraine are common chronic neurological disease. Epidemiologic studies and shared pathophysiology and treatment suggest that these two diseases overlap. However, migraine is often underestimated among patients with epilepsy. This study aimed to evaluate the prevalence of migraine and identify the related influencing factors among adult patients with epilepsy., Methods: Adult patients with epilepsy were recruited at the outpatient epilepsy clinic of 13 tertiary hospitals in China from February to September 2022. ID Migraine questionnaire was applied to evaluate for migraine. Both univariable and multivariable logistic regression models were used to explore the influencing factors of migraine., Results: A total of 1326 patients with epilepsy were enrolled in this study. The prevalence of migraine among patients with epilepsy was 19.2% (254/1326). In the multivariable analysis, being female (OR = 1.451, 95% CI: 1.068-1.975; p = 0.018), focal and focal to bilateral tonic-clonic seizures (OR = 1.583, 95% CI: 1.090-2.281; p = 0.015), and current seizure attack in the last 3 months (OR = 1.967, 95% CI: 1.282-3.063; p = 0.002) were the influencing factors for migraine. However, <10% of patients with epilepsy received analgesics for migraine., Significance: Approximately 20% of patients with epilepsy screened positive for migraine. Being female, focal and focal to bilateral tonic-clonic seizures, and current seizure attack in the last 3 months were the influencing factors for migraine. Neurologists should pay more attention to the screening and management of the migraine among patients with epilepsy in China., Plain Language Summary: Epilepsy and migraine are common chronic neurological disease with shared pathophysiological mechanisms and therapeutic options. However, migraine is often underestimated among patients with epilepsy. This multicenter study aimed to evaluate the prevalence of migraine and current status of treatment. In this study, approximately 20% of patients with epilepsy screened positive for migraine. Female, focal and focal to bilateral tonic-clonic seizures, and current seizure attack in the last 3 months were identified as independent influencing factors for migraine. Despite the high prevalence, the treatment for migraine was not optimistic, neurologists should pay more attention to the screening and management of migraine., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

In this study, novel chitosan/polyethylene oxide/Ti 3 C 2 T x 2D MXene nanosheets (CS/PEO/Ti 3 C 2 T x ) nanofibers were successfully prepared by a continuous electrospinning process. During the electrospinning process, induced by the syringe tip capillary effects and electric field force, the Ti 3 C 2 T x nanosheets were aligned along the direction of the nanofiber formation to occur a highly oriented structure. This well-ordered arrangement of the inorganic Ti 3 C 2 T x nanosheets within the organic polymer matrix nanofiber was similar with nacre-like 'brick-and-motar' structure to some extent, resulting in a marked increase in thermal stability and mechanical properties of the resultant CS/PEO/Ti 3 C 2 T x nanofiber. As 4 wt% of Ti 3 C 2 T x nanosheets loaded, the highest tensile strength of the CS/PEO/Ti 3 C 2 T x nanofiber mats was achieved as 31.7 MPa, about two times that of neat CS/PEO nanofibers. Uniformly dispersed Pd nanoparticles in size of about 1.6 nm have been successfully immobilized on the composite nanofiber with a solution impregnation process. With a loading as low as 0.2 mol% of Pd, the resultant Pd@CS/PEO/Ti 3 C 2 T x composite nanofiber catalysts were highly active for both Heck and Sonogashira coupling reactions with broad reactants application scope, and could be recycled 15 runs without significant loss of activities., 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.)

When designing footwear products, designers and kinesiologists usually factor in plantar surface pressure, motion capture data, and subjective comfort evaluations. However, these factors alone are not sufficient to guide the design of truly comfortable shoes. Pressure pain threshold (PPT) is a parameter that establishes a connection between psychological quantities and physical quantities. The purpose of this study was to construct a high-precision PPT map of the whole foot. Overall, 20 participants were included in this study, and an electronic, mechanical algometer was used to apply constant pressure to the participants' feet. A MATLAB graphical user interface was developed to simplify the data-collecting process and generate visual representations of the data. Finally, several high-precision unisex, different sex, and dominant side PPT maps were generated. The findings revealed that the foot dorsum area and the medial foot region exhibited the lowest PPTs (indicative of high sensitivity). Notably, the foot dorsum area near the toes displayed the highest pain sensitivity (indicative of the lowest PPT), while the plantar area demonstrated comparatively lower pain sensitivity. The heel area exhibited the lowest pain sensitivity. Simultaneously, the study observed that women's feet exhibited lower pain thresholds than men's. In the future, it is imperative to delve deeper into the correlation between short-term pain sensitivity and the daily, long-term exercise state, as well as other physiological data. This exploration will contribute to a more nuanced guide for footwear comfort design., 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.)

The rapid progress of intelligent transportation systems (ITS) has enabled the development of a highly spatiotemporally resolved vehicular VOC emission inventory. However, up to this point, the emission factors applied in vehicular VOC emission inventories worldwide are either independent of driving conditions or estimated by emission models, resulting in significant bias. In this study, by using the speed-dependent VOC emission factor measured online from a typical fleet in Guangzhou and collecting multiple sources of ITS data, we developed, for the first time, a link-level dynamic vehicular VOC emission inventory. The results reveal that the emission factors for vehicles at speeds higher than 50 km/h are only around 30 % of those at 5-20 km/h. Consequently, the total vehicular VOC emission in Guangzhou is estimated to be 16.19 kt in 2019, around 40 % lower than the estimates by the static emission inventory using the average emission factor during a short transient driving (STD) cycle. This discrepancy is mainly due to the much lower average speed of the STD cycle (20 km/h) compared to the average traffic speed on the road network (36 km/h). The discrepancy in VOC emissions was even higher for highways, with the static emission factors being 75-93 % higher than the speed-dependent ones. Such a large discrepancy underscores the necessity of applying localised speed-dependent emission factors to improve the estimation accuracy of vehicular VOC emissions. This study provides more accurate insights for policymakers in formulating targeted strategies to reduce vehicular VOC emissions and mitigate their contributions to ozone and PM 2.5 pollution in urban areas., 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.)

Four new p -terphenyl derivatives, talaroterphenyls A-D ( 1 - 4 ), together with three biosynthetically related known ones ( 5 - 7 ), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Compounds 1 - 3 are rare p -terphenyls, which are completely substituted on the central benzene ring by oxygen atoms; this is the first report of their isolation from natural sources. Their structures were elucidated through NMR spectroscopy, HRESIMS, and X-ray diffraction. Genome sequence analysis revealed that 1 - 7 were biosynthesized from tyrosine and phenylalanine, involving four key biosynthetic genes ( ttpB - ttpE ). These p -terphenyls ( 1 - 7 ) and 36 marine-derived terphenyl analogues ( 8 - 43 ) were screened for phosphodiesterase 4 (PDE4) inhibitory activities, and 1 - 5 , 14 , 17 , 23 , and 26 showed notable activities with IC 50 values of 0.40-16 μM. The binding pattern of p -terphenyl inhibitors 1 - 3 with PDE4 were explored by molecular docking analysis. Talaroterphenyl A ( 1 ), with a low cytotoxicity, showed obvious anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Furthermore, in the TGF-β1-induced medical research council cell strain-5 (MRC-5) pulmonary fibrosis model, 1 could down-regulate the expression levels of FN1, COL1, and α-SMA significantly at concentrations of 5-20 μM. This study suggests that the oxidized p -terphenyl 1 , as a marine-derived PDE4 inhibitor, could be used as a promising antifibrotic agent.

While many countries employed digital contact tracing to contain the spread of SARS-CoV-2, the contribution of cospace-time interaction (i.e., individuals who shared the same space and time) to transmission and to super-spreading in the real world has seldom been systematically studied due to the lack of systematic sampling and testing of contacts. To address this issue, we utilized data from 2230 cases and 220,878 contacts with detailed epidemiological information during the Omicron outbreak in Beijing in 2022. We observed that contact number per day of tracing for individuals in dwelling, workplace, cospace-time interactions, and community settings could be described by gamma distribution with distinct parameters. Our findings revealed that 38% of traced transmissions occurred through cospace-time interactions whilst control measures were in place. However, using a mathematical model to incorporate contacts in different locations, we found that without control measures, cospace-time interactions contributed to only 11% (95%CI: 10%-12%) of transmissions and the super-spreading risk for this setting was 4% (95%CI: 3%-5%), both the lowest among all settings studied. These results suggest that public health measures should be optimized to achieve a balance between the benefits of digital contact tracing for cospace-time interactions and the challenges posed by contact tracing within the same setting., (© 2024. The Author(s).)

Introduction: This study evaluates the efficacy of metagenomic next-generation sequencing (mNGS) in diagnosing spinal infections and developing therapeutic regimens that combine mNGS, microbiological cultures, and pathological investigations., Methods: Data were collected from 108 patients with suspected spinal infections between January 2022 and December 2023. Lesion tissues were obtained via C-arm assisted puncture or open surgery for mNGS, conventional microbiological culture, and pathological analysis. Personalized antimicrobial therapies were tailored based on these findings, with follow-up evaluations 7 days postoperatively. The sensitivity and specificity of mNGS were assessed, along with its impact on treatment and prognosis., Results: mNGS showed a significantly higher positive detection rate (61.20%) compared to conventional microbiological culture (30.80%) and PCT (28%). mNGS demonstrated greater sensitivity (79.41%) and negative predictive value (63.16%) than cultures (25% and 22.58%, respectively), with no significant difference in specificity and positive predictive value. Seven days post-surgery, a significant reduction in neutrophil percentage (NEUT%) was observed, though decreases in white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were not statistically significant. At the last follow-up, significant improved in Visual Analogue Scale (VAS) scores, Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores were noted., Conclusion: mNGS outperforms traditional microbiological culture in pathogen detection, especially for rare and critical pathogens. Treatment protocols combining mNGS, microbiological cultures, and pathological examinations are effective and provide valuable clinical insights for treating spinal infections., Competing Interests: The authors declare that they have no competing interests., (© 2024 Chen et al.)

Insufficient therapeutic strategies for acute kidney injury (AKI) necessitate precision therapy targeting its pathogenesis. This study reveals the new mechanism of the marine-derived anti-AKI agent, piericidin glycoside S14, targeting peroxiredoxin 1 (PRDX1). By binding to Cys83 of PRDX1 and augmenting its peroxidase activity, S14 alleviates kidney injury efficiently in Prdx1 -overexpression ( Prdx1 -OE) mice. Besides, S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production. Due to the limited druggability of S14 with low bioavailability (2.6%) and poor renal distribution, a pH-sensitive kidney-targeting dodecanamine-chitosan nanoparticle system is constructed to load S14 for precise treatment of AKI. l-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1 (Kim-1)-overexpressed cells. The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly. By encapsulation with micelles, the AUC 0‒ t , half-life time, and renal distribution of S14 increase 2.5-, 1.8-, and 3.1-fold, respectively. The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDP-glycosyltransferase (UGT)-mediated biotransformation. In summary, this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology, thereby driving advancements in marine drug development for AKI., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

Background: Major depression disorder (MDD) forms a common psychiatric comorbidity among patients with narcolepsy type 1 (NT1), yet its impact on patients with NT1 is often overlooked by neurologists. Currently, there is a lack of effective methods for accurately predicting MDD in patients with NT1., Objective: This study utilized machine learning (ML) algorithms to identify critical variables and developed the prediction model for predicting MDD in patients with NT1., Methods: The study included 267 NT1 patients from four sleep centers. The diagnosis of comorbid MDD was based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5). ML models, including six full models and six compact models, were developed using a training set. The performance of these models was compared in the testing set, and the optimal model was evaluated in the testing set. Various evaluation metrics, such as Area under the receiver operating curve (AUC), precision-recall (PR) curve and calibration curve were employed to assess and compare the performance of the ML models. Model interpretability was demonstrated using SHAP., Result: In the testing set, the logistic regression (LG) model demonstrated superior performance compared to other ML models based on evaluation metrics such as AUC, PR curve, and calibration curve. The top eight features used in the LG model, ranked by feature importance, included social impact scale (SIS) score, narcolepsy severity scale (NSS) score, total sleep time, body mass index (BMI), education years, age of onset, sleep efficiency, sleep latency., Conclusion: The study yielded a straightforward and practical ML model for the early identification of MDD in patients with NT1. A web-based tool for clinical applications was developed, which deserves further verification in diverse clinical settings., Competing Interests: Declaration of competing interest The authors report no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sleep quality is an important issue of public concern. This study, combined with sensor application, aims to explore the determinants of perceived comfort when using smart bedding to provide empirical evidence for improving sleep quality. This study was conducted in a standard sleep laboratory in Quanzhou, China, from March to April of 2023. Perceived comfort was evaluated using the Subjective Lying Comfort Evaluation on a seven-point rating scale, and body pressure distribution was measured using a pressure sensor. Correlation analysis was employed to analyze the relationship between perceived comfort and body pressure, and multiple linear regression was used to identify the factors of perceived comfort. The results showed that body pressure was partially correlated with perceived comfort, and sleep posture significantly influenced perceived comfort. In addition, height, weight, and body mass index are common factors that influence comfort. The findings highlight the importance of optimizing the angular range of boards based on their comfort performance to adjust sleeping posture and equalize pressure distribution. Future research should consider aspects related to the special needs of different populations (such as height and weight), as well as whether users are elderly and whether they have particular diseases. The design optimization of the bed board division and mattress softness, based on traditional smart bedding, can improve comfort and its effectiveness in reducing health risks and enhancing health status.

Four new cyclic pentapeptides, avellanins D-G ( 1 - 4 ), together with four known compounds ( 5 - 8 ), were isolated from a mangrove-derived Aspergillus fumigatus GXIMD 03099 fungus from Acanthus ilicifolius L. Their structures were elucidated by analysis of HRESIMS, NMR, and ESI-MS/MS data. Their absolute configurations were determined by X-ray diffraction analysis and Marfey's method. Compounds 1 - 8 were screened for insecticidal and antibacterial activities. Compound 2 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with an LC 50 value of 86.6 µM; compound 4 had weak activity against Vibrio harveyi with an MIC value of 5.85 µM.

Citrus canker, caused by Xanthomonas citri subsp. citri ( Xcc ), is a severe citrus disease. Currently, copper-containing pesticides are widely used to manage this disease, posing high risks to the environment and human health. This study reports the discovery of naturally occurring anti- Xcc compounds from a deep-sea fungus, Aspergillus terreus SCSIO 41202, and the possible mode of action. The ethyl acetate extract of A. terreus was subjected to bioassay-guided isolation, resulting in the discovery of eight anti- Xcc compounds ( 1 - 8 ) with minimum inhibitory concentrations (MICs) ranging from 0.078 to 0.625 mg/mL. The chemical structures of these eight metabolites were determined by integrative analysis of various spectroscopic data. Among these compounds, Asperporonin A ( 1 ) and Asperporonin B ( 2 ) were identified as novel compounds with a very unusual structural skeleton. The electronic circular dichroism was used to determine the absolute configurations of 1 and 2 through quantum chemical calculation. A bioconversion pathway involving pinacol rearrangement was proposed to produce the unusual compounds ( 1 - 2 ). Compound 6 exhibited an excellent anti- Xcc effect with a MIC value of 0.078 mg/mL, which was significantly more potent than the positive control CuSO 4 (MIC = 0.3125 mg/mL). Compound 6 inhibited cell growth by disrupting biofilm formation, destroying the cell membrane, and inducing the accumulation of reactive oxygen species. In vivo tests indicated that compound 6 is highly effective in controlling citrus canker disease. These results indicate that compounds 1 - 8 , especially 6 , have the potential as lead compounds for the development of new, environmentally friendly, and efficient anti- Xcc pesticides.

Ten azaphilones including one pair of new epimers and three new ones, penineulones A-E (1-5) with the same structural core of angular deflectin, were obtained from a deep-sea derived Penicillium sp. SCSIO41030 fermented on a liquid medium. Their structures including absolute configurations were elucidated using chiral-phase HPLC analysis, extensive NMR spectroscopic and HRESIMS data, ECD and NMR calculations, and by comparing NMR data with literature data. Biological assays showed that the azaphilones possessed no antitumor and anti-viral (HSV-1/2) activities at concentrations of 5.0 μM and 20 μM, respectively. In addition, azaphilones 8 and 9 showed neuroprotective effects against Aβ 25-35 -induced neurotoxicity in primary cultured cortical neurons at a concentration of 10 μM. Azaphilones 8 and 9 dramatically promoted axonal regrowth against Aβ 25-35 -induced axonal atrophy. Our study indicated that azaphilones could be promising lead compounds for neuroprotection.

Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, GSK3β inhibition countered the actions of Wnt antagonists on intestinal stem cells, resulting in impaired adenoma formation of telomere dysfunctional Apc-mutant cells. Thus, telomere dysfunction contributes to cancer initiation through altered stem cell dynamics, identifying an interception strategy for human APC-mutant cancers with shortened telomeres., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chlorella polysaccharides have been gaining increasing attention because of their high yield from dried Chlorella powder and their remarkable immunomodulatory activity. In this study, the major polysaccharide fraction, CPP-3a, in Chlorella pyrenoidosa, was isolated, and its detailed structure was investigated by analyzing the low-molecular-weight product prepared via free radical depolymerization. The results indicated that CPP-3a with a molecular weight of 195.2 kDa was formed by →2)-α-L-Araf-(1→, →2)-α-D-Rhap-(1→, →5)-α-L-Araf-(1→, →3)-β-D-Glcp-(1→, →4)-α-D-Glcp-(1→, →4)-α-D-GlcpA-(1→, →2,3)-α-D-Manp-(1→, →3,4)-α-D-Manp-(1→, →3,4)-β-D-Galp-(1→, →3,6)-β-D-Galp-(1→, and →2,3,6)-α-D-Galp-(1→ residues, branched at C2, C3, C4, or C6 of α/β-D-Galp and α-D-Manp, and terminated by α/β-L-Araf, α-L-Arap, α-D-Galp, and β-D-Glcp. Biological assays showed that CPP-3a significantly altered the dendritic morphology of immature dendritic cells (DCs). Enhanced CD80, CD86, and MHC I expression on the cell surface and decreased phagocytic ability indicated that CPP-3a could induce the maturation of DCs. Furthermore, CPP-3a-stimulated DCs not only stimulated the proliferation of allogeneic naïve CD4 + T cells and the secretion of IFN-γ, but also directly stimulated the activation and proliferation of CD8 + T cells through cross-antigen presentation. These findings indicate that CPP-3a can promote human DC maturation and T-cell stimulation and may be a novel DC maturation inducer with potential developmental value in DC 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 Ltd. All rights reserved.)

Within the hierarchical taxonomy of effective leadership, change-oriented leadership stands as a distinct and meaningful metacategory, primarily focusing on promoting change by communicating a compelling vision for the future. However, we consider whether there might be room to broaden the scope of change-oriented leadership by examining more negative-focused leadership behaviors. In this article, we explore the concept of vigilant leadership, which we suggest could be a change-oriented and negative-focused leadership style, and investigate its usefulness as a new leadership construct. In Study 1, we take preliminary steps toward developing a measure of vigilant leadership, employing content adequacy assessment and item response theory analysis. Drawing on the integrative trait-behavioral model of leadership effectiveness (DeRue et al., 2011), we further explore how vigilant leadership is associated with an array of antecedents (i.e., leader characteristics) and leadership outcomes. In Studies 2a and 2b, we present initial findings that leaders high on consideration of future consequences, prevention focus, general self-efficacy, and emotional intelligence might be more inclined to exhibit vigilant leadership. In Study 3, our results suggest that, even after controlling for the effect of visionary leadership (a type of positive-focused change-oriented leadership), vigilant leadership is positively related to follower felt responsibility for change, proactivity, specific proactive work behaviors (taking charge, voice, and problem prevention), teamwork proactivity, and teamwork proficiency. However, it does not seem to relate to follower proficiency, follower adaptivity, teamwork adaptivity, organizational citizenship behavior, positive affect toward the leader, leader-member exchange, or relational identification with the leader. With these preliminary findings, we encourage further discussion and investigation into the potential implications of this emerging construct. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Excessive daytime sleepiness (EDS) forms a prevalent symptom of obstructive sleep apnea (OSA) and narcolepsy type 1 (NT1), while the latter might always be overlooked. Machine learning (ML) models can enable the early detection of these conditions, which has never been applied for diagnosis of NT1., Objective: The study aimed to develop ML prediction models to help non-sleep specialist clinicians identify high probability of comorbid NT1 in patients with OSA early., Methods: Totally, clinical features of 246 patients with OSA in three sleep centers were collected and analyzed for the development of nine ML models. LASSO regression was used for feature selection. Various metrics such as the area under the receiver operating curve (AUC), calibration curve, and decision curve analysis (DCA) were employed to evaluate and compare the performance of these ML models. Model interpretability was demonstrated by Shapley Additive explanations (SHAP)., Results: Based on the analysis of AUC, DCA, and calibration curves, the Gradient Boosting Machine (GBM) model demonstrated superior performance compared to other machine learning (ML) models. The top five features used in the GBM model, ranked by feature importance, were age of onset, total limb movements index, sleep latency, non-REM (Rapid Eye Movement) sleep stage 2 and severity of OSA., Conclusion: The study yielded a simple and feasible screening ML-based model for the early identification of NT1 in patients with OSA, which warrants further verification in more extensive clinical practices., Competing Interests: The authors report no potential conflicts of interest in this work., (© 2024 Pan et al.)

Meroterpenoids of the ochraceopones family featuring a linear tetracyclic scaffold exhibit exceptional antiviral and anti-inflammatory activities. The biosynthetic pathway and chemical logic to generate this linear tetracycle, however, remain unknown. In this study, we identified and characterized all biosynthetic enzymes to afford ochraceopones and elucidated the complete biosynthetic pathway. We demonstrated that the linear tetracyclic scaffold of ochraceopones was derived from an angular tetracyclic precursor. A multifunctional cytochrome P450 OchH was validated to catalyze the free-radical-initiated carbon-carbon bond cleavage of the angular tetracycle. Then, a new carbon-carbon bond was verified to be constructed using a new aldolase OchL, which catalyzes an intramolecular aldol reaction to form the linear tetracycle. This carbon-carbon bond fragmentation and aldol reaction cascade features an unprecedented strategy for converting a common angular tetracycle to a distinctive linear tetracyclic scaffold in meroterpenoid biosynthesis., (© 2024 Wiley-VCH GmbH.)

Aberrant activation of the PI3K/AKT pathway is a driving factor in the development of prostate cancer. Therefore, inhibiting the function of the PI3K/AKT signaling pathway is a strategy for the treatment of prostate cancer. Ilicicolin C is an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501. Which has anti-inflammatory activity, but its activity against prostate cancer has not yet been elucidated. MTT assay, plate clone-formation assay, flow cytometry and real-time cell analysis technology were used to detect the effects of ilicicolin C on cell viability, proliferation, apoptosis and migration of prostate cancer cells. Molecular docking software and surface plasmon resonance technology were used to analyze the interaction between ilicicolin C and PI3K/AKT proteins. Western blot assay was performed to examine the changes in protein expression. Finally, QikProp software was used to simulate the process of ilicicolin C in vivo, and a zebrafish xenograft model was used to further verify the anti-prostate cancer activity of ilicicolin C in vivo. Ilicicolin C showed cytotoxic effects on prostate cancer cells, with the most significant effect on PC-3 cells. Ilicicolin C inhibited proliferation and migration of PC-3 cells. It could also block the cell cycle and induce apoptosis in PC-3 cells. In addition, ilicicolin C could bind to PI3K/AKT proteins. Furthermore, ilicicolin C inhibited the expression of PI3K, AKT and mTOR proteins and could also regulate the expression of downstream proteins in the PI3K/AKT/mTOR signaling pathway. Moreover, the calculations speculated that ilicicolin C was well absorbed orally, and the zebrafish xenograft model confirmed the in vivo anti-prostate cancer effect of ilicicolin C. Ilicicolin C emerges as a promising marine compound capable of inducing apoptosis of prostate cancer cells by counteracting the aberrant activation of PI3K/AKT/mTOR, suggesting that ilicicolin C may be a viable candidate for anti-prostate cancer drug development. These findings highlight the potential of ilicicolin C against prostate cancer and shed light on its mechanism of action., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An unprecedented di- seco -indole diterpenoid, peniditerpenoid A ( 1 ), and a rare N -oxide-containing indole diterpenoid derivative, peniditerpenoid B ( 2 ), together with three known ones ( 3 - 5 ), were obtained from the mangrove-sediment-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by the analysis of spectroscopic data, quantum chemical calculations, and X-ray diffraction analyses. Peniditerpenoid A ( 1 ) inhibited lipopolysaccharide-induced NF-κB with an IC 50 value of 11 μM and further effectively prevented RANKL-induced osteoclast differentiation in bone marrow macrophages. In vitro studies demonstrated that 1 exerted significant inhibition of NF-κB activation in the classical pathway by preventing TAK1 activation, IκBα phosphorylation, and p65 translocation. Furthermore, 1 effectively reduced the level of NFATc1 activation, resulting in the attenuation of osteoclast differentiation. Our findings suggest that 1 holds promise as an inhibitor with significant potential for the treatment of diseases related to osteoporosis.

Natural stilbenes have shown significant potential in the prevention and treatment of diseases due to their diverse pharmacological activities. Here we present a mild and effective Ti-catalyzed intermolecular radical-relay [2σ + 2π] cycloaddition of bicyclo[1.1.0]-butanes and 1,3-dienes. This transformation enables the synthesis of bicyclo[2.1.1]hexane (BCH) scaffolds containing aryl vinyl groups with excellent regio- and trans-selectivity and broad functional group tolerance, thus offering rapid access to structurally diverse stilbene bioisosteres., (© 2024. The Author(s).)

N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC-MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. Despite low bioavailability (0.024%), N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs., (© 2024. The Author(s).)

Two new cytochalasin derivatives, peniotrinins A ( 1 ) and B ( 2 ), three new citrinin derivatives, peniotrinins C-E ( 4 , 5 , 7 ), and one new tetramic acid derivative, peniotrinin F ( 12 ), along with nine structurally related known compounds, were isolated from the solid culture of Peniophora sp. SCSIO41203. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis, quantum chemical calculations, and the calculated ECD. Interestingly, 1 is the first example of a rare 6/5/5/5/6/13 hexacyclic cytochalasin. We screened the above compounds for their anti-prostate cancer activity and found that compound 3 had a significant anti-prostate cancer cell proliferation effect, while compounds 1 and 2 showed weak activity at 10 μM. We then confirmed that compound 3 exerts its anti-prostate cancer effect by inducing methuosis through transmission electron microscopy and cellular immunostaining, which suggested that compound 3 might be first reported as a potential anti-prostate methuosis inducer.

Objective: To investigate the influence of hyperglycemia on motor symptoms, especially axial signs, and potential mechanisms related to insulin resistance (IR) in patients with Parkinson's disease (PWP)., Methods: According to glycated hemoglobin (HbA1c) level, PWP were divided into the low-HbA1c and the high-HbA1c groups. Demographic information, glucose metabolism-related variables, Hoehn-Yahr stage, and motor function were compared between the two groups. Correlations between levels of HbA1c and the homeostatic model assessment (HOMA)-IR and motor function in PWP were further analyzed., Results: HbA1c level was significantly and positively correlated with the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score, axial signs subscore, the Timed Get Up and Go test time, the center of pressure displacement of standing with eyes open and closed, and significantly and negatively correlated with the 10-m walk test comfortable gait speed. HOMA-IR level was significantly and negatively correlated with 10-m walk test comfortable gait speed, but not with others., Conclusions: PWP with high HbA1c showed worse axial symptoms, including dysfunction of automatic walking, dynamic balance, and postural control than those with low HbA1c. In PWP, the effects of hyperglycemia on automatic walking speed may be associated with the IR-related mechanisms, and the effects on dynamic balance and postural control may be related to mechanisms other than IR., (© 2023. Fondazione Società Italiana di Neurologia.)

Adults with restless sleep disorder (RSD) have never been studied clinically and polysomnographically. This study aimed to describe the clinical manifestation, duration, and distribution of sleep-related movements in adult patients with restless sleep disorder. Patients who had performed VPSG from Jan 2021 to Jan 2022 and met the diagnosis criteria of RSD were enrolled in the study. Patients' bed partners were also interviewed or telephoned in identifying this disorder. Scoring of movements during sleep was according to the diagnosis criteria of RSD and scoring of large muscle group movements during sleep proposed by the International RLS Study Group in 2020 and 2021, respectively. The clinical manifestation, the distribution of sleep stage as well as the types and duration of the movements were carefully recorded and analyzed. We included ten patients in the study with a mean age of 27.6 years (range 22-38). There was a male prevalence in adults with RSD. The study highlighted the findings from video-polysomnography, which indicated frequent sleep-related movements occurring throughout the Night. These movements were most prominent during N1 and N2 sleep stage, followed by REM sleep, while fewer movements were observed during N3 sleep. Adults with RSD experienced significant daytime functioning impairments, including non-refreshing sleep, daytime fatigue/sleepiness, and mood disturbance. Two of the patients in the study were diagnosed with anxiety and depression, further underscoring the impact of RSD on mental health. Adult patients also suffer from severe RSD, and the RSD that originates in childhood tends to persist into adulthood. In these cases, longer duration of the disease and poor sleep quality may be associated with an increased risk of developing psychiatric comorbidities. Our cases represent an objectively documented type of RSD in younger adult patients., Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-024-00524-1., Competing Interests: Conflict of interestThe other authors report no financial disclosure and no conflict of interest statement.Ethical approvalAll authors have seen and approved of this manuscript. The study was approved by Xijing Hospital Research Ethics Committee, all authors reported that they have conformed to the principles of ethics in publishing and ethical guidelines for journal publication, and written informed consent was obtained from the parents regarding publication of this report. None of the authors has any conflict of interest to disclose., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Two new dihydroisocoumarins, exserolides L and M (1 and 2), along with six known compounds (3-8) were isolated from the extract of the marine-sponge-derived fungus Setosphaeria sp. SCSIO41009. Their structures were established by spectroscopic analyses. The absolute configurations of two new compounds were determined by modified Mosher's method and ECD data. Compounds 1 and 4 showed significant antiviral activities against A/Puerto Rico/8/34 H274Y (H1 N1) with IC 50 values of 4.07±0.76 μM and 20.06±4.85 μM, respectively., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)