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Abstract The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.9 tonnes of cryogenic liquid xenon (8.5 tonnes total mass in cryostat). The experiment is expected to extend the sensitivity to WIMP dark matter by more than an order of magnitude compared to XENON1T, thanks to the larger active mass and the significantly reduced background, improved by novel systems such as a radon removal plant and a neutron veto. This article describes the XENONnT experiment and its sub-systems in detail and reports on the detector performance during the first science run.

Intestinal health heavily depends on establishing a mucus layer within the gut with physical properties that strike a balance between being sufficiently elastic to keep out harmful pathogens yet viscous enough to flow and turnover the contents being digested. Studies investigating dysfunction of the mucus layer in the intestines are largely confined to animal models, which require invasive procedures to collect the mucus fluid. In this work, we develop a nondestructive method to study intestinal mucus. We use an air–liquid interface culture of primary human intestinal epithelial cells that exposes their apical surface to allow in situ analysis of the mucus layer. Mucus collection is not only invasive but also disrupts the mucus microstructure, which plays a crucial role in the interaction between mucus and the gut microbiome. Therefore, we leverage a noninvasive rheology technique that probes the mechanical properties of the mucus without removal from the culture. Finally, to demonstrate biomedical uses for this cell culture system, we characterize the biochemical and biophysical properties of intestinal mucus due to addition of the cytokine IL-13 to recapitulate the gut environment of Nippostrongylus brasiliensis infection.

Excessive environmental vibrations generated by urban traffic pose adverse effects on nearby structures and residents. These vibrations are predominantly carried by surface waves, which are localized within the surface layer of soil. The isolation of surface waves through the embedding of periodic wave barriers in soils between the source and the receiver has gained significant attention in recent years. In this paper, a novel approach is proposed for isolating surface waves induced by urban traffic through the use of variable depth infilled trenches. This innovative design not only achieves efficient surface wave isolation but also minimizes the consumption of structural materials. Based on the measured dominant frequency range of rail transit and the available soil parameters, variable depth infilled trenches are designed with suitable dimensions. The eigenvalue equation is solved using the finite element method to derive the dispersion relations and bandgap of identical regularly spaced trenches. To study the efficacy of the proposed structure, a finite element model of the soil-infilled trench system is developed using COMSOL. The mechanism underlying the isolation of surface wave is elucidated, and the effect of variable angle α on the isolation efficiency within 40-50 Hz η 40-50Hz of surface waves is studied. The results of this study reveal that for variable angle α of 15°, the surface wave isolation efficiency within 40-50 Hz η 40-50Hz is 90.9 % and 92.5 % for uniformly increasing depth infilled trenches and uniformly decreasing depth infilled trenches, respectively. Although the surface wave isolation efficiencies predicted for the variable depth infilled trench arrangements are only 93.8 % and 95.5 % of those predicted for the regularly spaced identical infilled trenches, the variable depth arrangements result in a remarkable 34 % reduction in material usage. These findings highlight the potential of the proposed variable depth infilled trenches as a cost-effective and efficient solution for surface wave isolation., 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.)

Traditional fungi β-glucan commonly possesses high molecular weight with poor water solubility, which remains significant challenge in the drug development and medical application. Water-soluble β-glucan with high molecular weight (dHSCG) of 560 kDa, low molecular weight (dLSCG) of 60 kDa, and sulfated derivative (SCGS) with a molecular weight of 146 kDa and sulfate degree at 2.04 were obtained through well-controlled degradation and sulfated modification from Saccharomyces cerevisiae in this study. The structural characteristics were confirmed as β-1,3/6-glucan by FT-IR and NMR spectroscopy. Carbohydrate microarrays and surface plasmon resonance revealed distinct and contrasting binding affinities between the natural β-glucans and sulfated derivatives. SCGS exhibited strong binding to FGF and VEGF, while natural β-glucan showed no response, suggesting its potential as a novel antitumor agent. Moreover, SCGS significantly inhibited the migration rate of the highly metastatic melanoma (B16F10) cells. The lung metastasis mouse model also demonstrated that SCGS significantly reduced and eliminated the nodules, achieving an inhibition rate of 86.7% in vivo, with a dramatic improvement in IFN-α, TNF-α, and IL-1β levels. Through analysis of protein content and distribution in lung tissues, the anti-tumor and anti-metastasis mechanism of SCGS involves the regulation of degrading enzymes to protect extracellular matrix (ECM), as well as the reduction of angiogenic factor release. These findings provide a foundation for exploring the potential of SCGS in the development of new anti-tumor and anti-metastasis drugs and open up a new field in cancer 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.)

The effectiveness of bioretention cells for heavy metals (HMs) and microplastics (MPs) removal from stormwater runoff has been demonstrated. Knowledge of the mechanisms that dictate the interactions between MPs and HMs would be helpful in pollution control. In this study, the performances of different water-soil-plant bioretention cells for HMs removal through the interception of polyethylene MPs (PE-MPs) were investigated. The results showed that PE-MPs bound to HMs and preferentially tended to bind to Pb (32%-44%) in the complex HMs (Cu, Zn, Cd, and Pb). This could be the reason that the concentration of Pb significantly increased in the effluent under low-intensity simulated rainfall events over a long duration. The accumulation of 1.49 g/kg PE-MPs caused a significant soil pH value decrease and a notable soil zeta potential increase in the bioretention cell, while the low sand/silt ratio media buffered this process. The retention of PE-MPs increased 138.5% in the 0-10 cm soil surface layer when the sand/silt ratio reduced from 2:1 to 1:1 and planted with Canna indica. Meanwhile, PE-MPs amplified the instability of Zn removal in bioretention cells under low-intensity rainfall events in long-duration, high silt percentage substrate and vegetation coverage. The study would contribute to developing a long-term management program for PE-MPs and HMs trapped in bioretention cells to reduce the risk of pollution transport., 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.)

Synergistic reduction of air pollutants and carbon dioxide (CO 2 ) emissions is currently a key environmental policy in China, yet provincial-level studies remain scarce. To fill the gap, this study developed a coupled emission inventory from 2013 to 2020 in Shanxi, a coal-dependent province critical to China's energy security. This facilitated the investigation of emission trends, primary sources, synergistic effects, and spatial distribution. The results show that, while air pollutant emissions decreased significantly during the study period, CO 2 emissions increased slightly. The main emitters of SO 2 , NO x , and CO 2 were identified as power, heating, industrial boilers, and residential coal combustion. The iron and steel industry contributed significantly to PM 2.5 emissions, coke production to VOCs, and vehicles to NO x and VOCs. NH 3 emissions were mainly attributed to fertilizer use and livestock. Synergistic reductions were evident in coal-related sources, especially industrial boilers and residential coal combustion, underlining the importance of optimizing the energy structure. Anthropogenic emissions were concentrated in basins with poor dispersion conditions. Taiyuan, Yuncheng, and Linfen emerged as key areas for synergistic reduction efforts. This study provides important insights for environmental policy development in Shanxi and other coal-dependent regions., 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.)

Background: Hepatocellular carcinoma (HCC) is a common cancer that is fatal and has a dismal prognosis. Obovatol (Ob), a novel lignan derived from the leaf and stem bark of Magnolia obovata Thunb, has exhibited anti-tumor effect on diverse tumors. However, its effect and mechanisms on HCC remain to be further explored., Methods: Huh7 and Hep3B cells, as well as BALB/c nude mice were used to determine the function and mechanisms of Ob on growth, invasion and immune escape by cell counting kit-8, transwell, enzyme-linked immunosorbent assay (ELISA) and western blot experiments., Results: Ob reduced the cell viability of Huh7 and Hep3B cells, with a IC50 value of 57.41 µM and 62.86 µM, respectively. Ob declined the invasion ability, the protein expression of N-cadherin and the concentrations of IL-10 and TGF-β, whereas increased the E-cadherin expression and the contents of IFN-γ and IL-2 in Hep3B and Huh7 cells. Mechanically, Ob decreased the protein level of p-JAK/JAK, p-STAT3/STAT3 and PD-L1, which was partly restored with the treatment of RO8191, an activator of JAK/STAT3 axis. The effect of Ob on the cell viability, the invasion ability, the protein level of N-cadherin and E-cadherin, and the concentrations of IL-10, TGF-β, IFN-γ and IL-2 in both Hep3B and Huh7 cells was reversed with the management of RO8191. In vivo, Ob reduced tumor volume and weight, the level of N-cadherin, PD-L1, p-JAK/JAK, and p-STAT3/STAT3, with an elevated expression of E-cadherin and IFN-γ., Conclusion: Ob downregulated the JAK/STST3/PD-L1 pathway to attenuate the growth, invasion and immune escape of HCC., 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.)

Background: A dramatic increase in fetal situs inversus diagnoses by ultrasound in the months following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge of December 2022 in China led us to investigate whether maternal SARS-CoV-2 exposure could be associated with elevated risk of fetal situs inversus., Methods: In this multi-institutional, hospital-based, matched case-control study, we investigated pregnant women who underwent ultrasonographic fetal biometric assessment at gestational weeks 20-24 at our hospitals. Each pregnant woman carrying a situs inversus fetus was randomly matched with four controls based on the date of confinement. Relevant information, including SARS-CoV-2 infection, and other potential risk factors were collected. Conditional logistic regression was used to test possible associations between fetal situs inversus and SARS-CoV-2 infection at different gestational weeks as well as individual risk factors., Findings: A total of 52 pregnant women diagnosed with fetal situs inversus between January 1 and October 31, 2023 and 208 matched controls with normal fetuses were enrolled. We found no association between an increased risk of fetal situs inversus with gestational SARS-CoV-2 infection or with other risk factors. However, fetal situs inversus was significantly associated with SARS-CoV-2 infection specifically in gestational weeks 4-6 (adjusted odds ratio [aOR] 6.54 [95% confidence interval 1.76-24.34]), but not with infection at other gestational ages, after adjusting for covariates., Conclusions: Increased risk of fetal situs inversus is significantly associated with maternal SARS-CoV-2 infection at gestational weeks 4-6, corresponding to the fetal developmental window for visceral lateralization in humans., Funding: National Key R&D Program of China, etc., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ferroptosis represents a nonapoptotic type of programmed cell death induced by excessive intracellular iron accumulation. Ferroptosis is an essential driver of the pathogenesis of Alzheimer's disease (AD). Tetrahedral framework nucleic acids (tFNAs) are a novel type of nanoparticle with superior antiapoptotic capacity and excellent biocompatibility. However, the effect of tFNAs on Aβ triggered ferroptosis, cognitive and synaptic impairments in AD remains unknown., Methods: N2a cells were treated with Aβ combined with/without tFNAs. Cell viability and levels of Fe 2+ , lipid peroxidation, MDA, LDH, and GSH were examined. RNA sequencing was applied to explore dysregulated ferroptosis related genes. Seven-month-old APP/PS1 mice were intranasally administrated with tFNAs for two weeks. Fluorescence imaging was used to detect the tFNAs distribution in the brain. Novel object recognition (NOR) test followed by Morris water maze (MWM) was used to test the learning and memory performance of mice. Golgi staining, Western blot, and immunofluorescence staining were used to examine synaptic plasticity., Results: tFNAs promoted cell viability and GSH levels, reduced the levels of Fe 2+ , lipid peroxidation, MDA, and LDH in N2a cells treated with Aβ. RNA sequencing revealed that tFNAs reversed the promotive effect of Aβ on ferroptosis driver Atf3 gene and suppressive effect on ferroptosis suppressors Rrm2 and Furin genes. Fluorescence imaging confirmed the brain infiltration of tFNAs. tFNAs rescued synaptic and memory impairments, and ferroptosis in seven-month-old APP/PS1 mice., Conclusions: Collectively, tFNAs inhibited Aβ-mediated ferroptosis and ameliorated cognitive and synaptic impairments in AD mice. tFNAs may serve as novel option to deal with AD., (© 2024. The Author(s).)

Hepatitis B virus (HBV) infection is associated with the progression of liver disease. Occult HBV infection (OBI) is defined as the existence of detectable HBV DNA in HBV surface antigen negative individuals. However, HBV DNA is negative in serum while HBV surface antigen remains positive in incompletely cured chronic HBV infection. Hence, combined detection of HBV surface antigen and HBV DNA is essential for the accurate detection and rehabilitation of HBV infection. Therefore, a multiplex detection strategy based on branched DNA nanostructures was developed. The single-stranded segment of a branched DNA nanostructure (segments of S4 and S2) assembled by four single-stranded DNA was hybridized with the aptamer of HBV surface antigen and DNA hairpin to construct a DNA nanosensor, which can achieve high specificity identification and highly sensitive fluorescence responses to the targets. The detection limits of the developed nanosensor for HBV and HBV DNA are 50 pM and 5 nM, respectively. The combined detection of HBV surface antigen and HBV DNA provides a new insight for more thorough diagnostic evaluation of HBV infection and rehabilitation.

Thin-film composite (TFC) membranes, featuring nanoscale film thickness and customizable pore structures, hold promise for solute-solute separations. However, achieving on-demand molecular sieving requires fine control over the membrane microstructure. Here, the concept of physical and chemical dual confinement (PCDC) is introduced to fabricate loose-structured TFC membranes via confined interfacial polymerization (IP). This concept leverages the synergistic effects of physically restricted monomer diffusion and a chemically inhibited reaction to achieve controlled nanofilm growth. Dorsal addition of the aqueous phase to the hydrogel reduces the diamine diffusion via electrostatic and H-bonding interactions within its nanopores. The prepassivation of hydrazine using acid protonation effectively weakens its ability for nucleophilic reactivity. This confined IP between twisted TFPA and short-chain hydrazine yielded loosely structured azine-linked nanofilms, which displayed a high permeability of 53.4 LMH bar -1 and effective differentiation of binary mixtures. This PCDC concept offers a useful guideline to finely tailor polymeric nanofilms for precise separations.

Mollusca, the second-most diverse animal phylum, is estimated to have over 100,000 living species with great genetic and phenotypic diversity, a rich fossil record, and a considerable evolutionary significance. Early work on molluscan systematics was grounded in morphological and anatomical studies. With the transition from oligo gene Sanger sequencing to cutting-edge genomic sequencing technologies, molecular data has been increasingly utilised, providing abundant information for reconstructing the molluscan phylogenetic tree. However, relationships among and within most major lineages of Mollusca have long been contentious, often due to limited genetic markers, insufficient taxon sampling and phylogenetic conflict. Fortunately, remarkable progress in molluscan systematics has been made in recent years, which has shed light on how major molluscan groups have evolved. In this review of molluscan systematics, we first synthesise the current understanding of the molluscan Tree of Life at higher taxonomic levels. We then discuss how micromolluscs, which have adult individuals with a body size smaller than 5 mm, offer unique insights into Mollusca's vast diversity and deep phylogeny. Despite recent advancements, our knowledge of molluscan systematics and phylogeny still needs refinement. Further advancements in molluscan systematics will arise from integrating comprehensive data sets, including genome-scale data, exceptional fossils, and digital morphological data (including internal structures). Enhanced access to these data sets, combined with increased collaboration among morphologists, palaeontologists, evolutionary developmental biologists, and molecular phylogeneticists, will significantly advance this field., (© 2024 Cambridge Philosophical Society.)

1. Valgus-varus deformity (VVD) is a disease that severely affects leg function in broilers and for which there is no effective control method current available. Although DNA methylation has an important impact on most physiological and pathological processes, its involvement in skeletal muscle growth and development in VVD broilers is unknown. In this study, genome-wide DNA methylation was analysed in VVD-affected and normal broilers using whole genome resulphite sequencing.2. The results showed that in the cytosine-phosphoric acid-guanine (CG) sequence environment there was a methylation rate of about 55% and 4,265 differentially methylated regions (DMRs) were found in the CG. Of these, 550 were located in the promoter, 547 in the exon region, and 1,718 in the intron region.3. All differentially methylated genes (DMGs) were analysed for enrichment of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The GO was enriched in pathways related to protein degradation such as proteasome complex, endopeptidase complex and extracellular region. The KEGG pathways were enriched in signalling pathways related to protein degradation and catabolism such as proteasome, nitrogen metabolism, adherens junction and alanine.4. Protein interactions analysis revealed that FOS, MYL9, and FRAS1 had a high degree of interactions, in which the DNA methylation level of the MYL9 promoter region was negatively correlated with mRNA expression level. Further studies showed that 5-azacytidine (5-AzaC) inhibited DNMT1 and DNMT3A gene expression and promoted MYL9 expression.5. This study systematically investigated overall DNA methylation patterns in the leg muscle of VVD and normal broilers. It screened common differential genes in conjunction with transcriptomic data to further identify genes associated with muscle growth and development. This study provides new insights to better understand the pathogenesis of VVD from an epigenetic perspective.

The visualization of transparent specimens in traditional light microscopy is impeded by insufficient intrinsic contrast, prompting the development of advanced contrast-enhancement methodologies to transmute minute phase discrepancies into detectable amplitude alterations. While existing methods excel in either phase-contrast imaging (contrast-enhanced image of whole objects) or relief-like imaging (deceptive three-dimensional images), it would be of great significance to seamlessly integrate both capabilities in the same device. Here, we propose a novel metasurface-assisted half-side phase-contrast technique capable of simultaneous phase-contrast and relief-like imaging across the visible spectrum, which is realized by introducing a ±π/2 phase shift to a half-side diffracted wave emitted by the objects. Our method showcases successful application to diverse specimens, including a transparent silica disk and a frog egg cell. Our work substantiates high-quality microscopic imaging of various transparent specimens, which has profound implications in cellular biology, materials science, and medical diagnostics.

G-quadruplexes (G4s) are four-stranded structures formed by guanine-rich sequences. While their structures, properties, and applications have been extensively studied, an understanding of their folding processes remains limited. In this study, we investigated the folding of the sequence d[(G 3 T 2 ) 3 G 3 ] in potassium solutions, focusing on the impact of a folding intermediate on the overall folding process. Our results indicate that this sequence eventually folds into a parallel G4 structure, either directly or through an antiparallel conformation intermediate, suggesting the existence of a specific competitive folding process. Detailed kinetic analysis using stopped-flow techniques reveals that the antiparallel conformation forms much faster than the parallel one. This antiparallel G4 slowly converts to the thermodynamically favored parallel topology, thus slowing the overall folding rate. As a result, the formation of the parallel quadruplex via an antiparallel G4 intermediate is slower than the direct process, indicating that this antiparallel conformation negatively impacts the overall folding process in a temperature-dependent manner. Interestingly, sodium was shown to facilitate the conversion from antiparallel to parallel. These analyses highlight the complexity of the G4 folding process, which is crucial for most biological applications.

Objective: To examine the influence of postpartum exercise on maternal depression and anxiety., Design: Systematic review with random effects meta-analysis and meta-regression., Data Sources: Online databases up to 12 January 2024, reference lists, recommended studies and hand searches., Eligibility Criteria: Randomised controlled trials (RCTs) and non-randomised interventions of any publication date or language were included if they contained information on the Population (postpartum people), Intervention (subjective or objective measures of frequency, intensity, duration, volume, type, or mode of delivery of exercise), Comparator (no exercise or different exercise measures), and Outcome (postpartum depression, anxiety prevalence, and/or symptom severity)., Results: A total of 35 studies (n=4072) were included. Moderate certainty evidence from RCTs showed that exercise-only interventions reduced the severity of postpartum depressive symptoms (19 RCTs, n=1778, SMD: -0.52, 95% CI -0.80 to -0.24, I 2 =86%, moderate effect size) and anxiety symptoms (2 RCTs, n=513, SMD: -0.25, 95% CI -0.43 to -0.08, I 2 =0%, small effect size), and the odds of postpartum depression by 45% (4 RCTs, n=303 OR 0.55, 95% CI 0.32 to 0.95, I 2 =0%) compared with no exercise. No included studies assessed the impact of postpartum exercise on the odds of postpartum anxiety. To achieve at least a moderate reduction in the severity of postpartum depressive symptoms, postpartum individuals needed to accumulate at least 350 MET-min/week of exercise (eg, 80 min of moderate intensity exercise such as brisk walking, water aerobics, stationary cycling or resistance training)., Conclusions: Postpartum exercise reduced the severity of depressive and anxiety symptoms and the odds of postpartum depression., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Macroalgae play a crucial role in blue carbon ecosystems, yet their elemental compositions in the Red Sea are not well documented. This study examined the concentrations of 22 elements in 161 macroalgae blade samples from 19 species (5 unidentified) across 3 phyla in the Saudi Arabian Red Sea. Macroalgae blades collected from coral reef habitats exhibited higher concentrations of K, As, and Sr compared to those from seagrass meadows, but had lower levels of total nitrogen (TN), Na, Mg, Al, P, S, Cr, Mn, Fe, and Zn. These differences may be attributed to the limited or absent sediment in coral reef habitats, as sediment in seagrass meadows acts as a trap for heavy metals, influencing element accumulation. In the Southern Red Sea, macroalgae blades showed lower Sr levels but higher total organic carbon (TOC), TN, P, and Cd than those in the North, a trend influenced by nutrient inflows from the Indian Ocean and the semi-enclosed structure of the Red Sea. The study found that macroalgae blades had lower mean TOC and TN content than seagrass and mangrove leaves from the same research cruises but higher levels of Al, Cr, Ni, Cu, Zn, As, Mo, Cd, and Pb. Among the surveyed red, green, and brown macroalgae blades, Halymenia sp., Caulerpa taxifolia, and Dictyota sp. had the highest TOC, TN, and P contents, while Amphiroa fragilissima, Udotea flabellum, and Padina sp. had higher trace metal contents. Notably, some macroalgae blades, including red macroalgae A. fragilissima, green macroalgae Halimeda tuna, U. flabellum, and brown macroalgae Padina pavonica, Turbinaria ornata, collected from Al Birk, Al Lith, Thuwal, Yanbu, and Al Wajh exhibited concerning levels of Cr (~10.9 mg kg -1 ) and Ni (~27.2 mg kg -1 ), surpassing toxicity thresholds. These findings emphasize the urgent need for effective pollution mitigation measures to protect these marine ecosystems., 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.)

Sewage sludge is a critical reservoir for biological pollutants, and its harmless disposal remains a major issue. Quaternary ammonium compounds (QACs) as typical household disinfectants are inevitably concentrated in sewage sludge, and have the potential to affect human pathogenic bacteria (HPBs) that remain poorly understood. This study found that the relative abundance of HPBs in digesters was decreased by 10 - 20 % at low QACs dose, but increased by 238 - 591 % at high QACs dose. Mechanistic analysis revealed that low QACs doses promoted functional hydrolytic/fermentative bacteria and their metabolism by stimulating extracellular polymeric substances secretion and enhancing resistance to QACs. Conversely, high QAC doses decreased microbial biomass and developed QACs and antibiotic resistance of HPBs by increasing cell membrane permeability and triggering oxidative stress, resulting in deteriorating sanitation performance. These findings provide advanced insights into the potential function and hazards of exogenous QACs on the biosafety of digestate., 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 Ltd.)

Autosomal recessive spinal muscular atrophy (SMA) is a leading cause of infant and child mortality, with homozygous deletion in exon 7 of the SMN1 gene being a major genetic cause. However, routine genetic testing methods may overlook structural variants outside of exon 7, potentially leading to misdiagnosis of SMA patients. Here, we reported two Chinese SMA patients who primarily exhibited developmental delays. Physical examinations revealed markedly reduced muscle strength and tone in their extremities, and electromyography suggested extensive neurogenic damage in the anterior horn of the spinal cord. The MLPA results indicated a single copy number of SMN1 in both patients, which is inconsistent with the typical genetic pattern of SMA. Through RNA sequencing and ultra-long read sequencing, we ultimately identified a rare structural variant involving the deletion of exons 2a-5 in both unrelated patients. This confirmed the presence of compound heterozygous variants in the SMN1 gene as the actual genetic cause. To our knowledge, this is the first case where a combination of RNA sequencing and ultra-long read sequencing has been used to diagnose SMA. We demonstrated the significant value of RNA sequencing in cases where children are highly suspected of having SMA but present negative results in routine genetic testing. This underscores the crucial role of accurate genetic testing methods in achieving early diagnosis of SMA., (© 2024 Wiley Periodicals LLC.)

Background/aims: This study aimed to assess the impact of INTERCEPT Foam Spray (IFS) application on delayed endoscope reprocessing through microbiological surveillance culture (MSC)., Methods: A quasi-experimental, matched-comparison pilot study was conducted using gastrointestinal endoscopy. IFS was applied to the endoscopes after precleaning and before reprocessing the next day. An equal number of endoscopes, matched by endoscope type, were subjected to routine reprocessing. The MSC were subjected to high-level disinfection to detect any contamination. Data were analyzed using the chi-square test or Fisher exact test (categorical data) and Student t-test (continuous data)., Results: In total, 150 MSCs were collected from 42 endoscopes. Positive MSCs were observed in 4.0% (4/75) of the sprayed group and 1.3% (1/75) of the control group (95% confidence interval [CI], 30.34-0.31; p>0.05), all of which were contributed by colonoscopes. Colonoscope were more prone to positive MSC (mean difference in percentage, p<0.05). Mean spraying hours were not associated with detected growth (11.7% vs. 13.6; 95% CI, 1.43 to -5.27; p>0.05), with environmental and skin flora being the primary contaminants., Conclusions: IFS may be applied when delayed endoscope processing is necessary, but with caution when applied to colonoscopes. However, further research is warranted to verify the result.

Polyploidization plays a crucial role in plant evolution and is becoming increasingly important in breeding. Structural variations and epigenomic repatterning have been observed in synthetic polyploidizations. However, the mechanisms underlying the occurrence and their effects on gene expression and phenotype remain unknown. Here, we investigated genome-wide large deletion/duplication regions (DelDups) and genomic methylation dynamics in leaf organs of progeny from the first eight generations of synthetic tetraploids derived from Chinese cabbage (Brassica rapa L. ssp. pekinensis) and cabbage (Brassica oleracea L. var. capitata). One- or two-copy DelDups, with a mean size of 5.70 Mb (400 kb to 65.85 Mb), occurred from the first generation of selfing and thereafter. The duplication of a fragment in one subgenome consistently coincided with the deletion of its syntenic fragment in the other subgenome, and vice versa, indicating that these DelDups were generated by homoeologous exchanges (HEs). Interestingly, the larger the genomic syntenic region, the higher the frequency of DelDups, further suggesting that the pairing of large homoeologous fragments is crucial for HEs. Moreover, we found that the active transcription of continuously distributed genes in local regions is positively associated with the occurrence of HE breakpoints. In addition, the expression of genes within DelDups exhibited a dosage effect, and plants with extra parental genomic fragments generally displayed phenotypes biased toward the corresponding parent. Genome-wide methylation fluctuated remarkably, which did not clearly affect gene expression on a large scale. Our findings provide insights into the early evolution of polyploid genomes, offering valuable knowledge for polyploidization-based breeding., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Color centers, arising from zero-dimensional defects, exploit quantum confinement to access internal electron quantum degrees of freedom, holding potential for quantum technologies. Despite intensive research, the structural origin of many color centers remains elusive. In this study, we employ in-situ cathodoluminescence scanning transmission electron microscopy combined with integrated differential phase contrast imaging to examine how defect configuration in tungsten sulfide determines color-center emission. Using an 80-kV accelerated electron beam, defects were deliberately produced, visualized, excited in situ and characterized in real time in monolayer WS 2 within hBN|WS 2  | hBN heterostructures at 100 K. These color centers were simultaneously measured by cathodoluminescence microscopy and differentiated by machine learning. Supported by DFT calculations, our results identified a crucial sulfur vacancy configuration organized into featured vacancy pairs, generating stable and bright luminescence at 660 nm. These findings elucidate the atomic-level structure-exciton relationship of color centers, advancing our understanding and quantum applications of defects in 2D materials., (© 2024. The Author(s).)

Dysfunctional renal tubular epithelial cells, induced by high glucose, are commonly observed in the kidney tissues of diabetic nephropathy (DN) patients. The epithelial-mesenchymal transition (EMT) of these cells often leads to renal interstitial fibrosis and kidney damage in DN. High glucose also triggers mitochondrial damage and apoptosis, contributing further to the dysfunction of renal tubular epithelial cells. Cellular senescence, a recognized characteristic of DN, is primarily caused by high glucose. However, it remains unclear whether high glucose-induced cellular senescence in DN exacerbates the functional impairment of tubular epithelial cells. In this study, we examined the relationship between EMT and cellular senescence in kidney tissues from streptozotocin (STZ)-induced DN and HK-2 cells treated with high glucose (HG). We also investigated the impact of HG concentrations on tubular epithelial cells, specifically mitochondrial dysfunction, cellular senescence and apoptosis. These damages were primarily associated with the secretion of cytokines (such as IL-6, and TNF-α), production of reactive oxygen species (ROS), and an increase of intracellular Ca 2+ . Notably, resveratrol, an anti-aging agent, could effectively attenuate the occurrence of EMT, mitochondrial dysfunction, and apoptosis induced by HG. Mechanistically, anti-aging treatment leads to a reduction in cytokine secretion, ROS production, and intracellular Ca 2+ levels., Competing Interests: Declaration of competing interest All authors declare no competing interests. We declare that neither the entire paper nor any part of its content has been published or has been accepted elsewhere. If accepted, it will not be published elsewhere in the same form, in English or in any other languages, including electronic form without the written consent of the copyright-holder., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This paper evaluates the accuracy and safety of a long bone fracture reduction robot under different surgical modes., Methods: A long bone fracture reduction robot system was developed, which can be controlled via an autonomous surgical mode or a master-slave surgical mode. Reduction experiments were conducted on a long bone cadaver specimen. The accuracy and safety of the robotic reduction were compared across the different surgical modes., Results: When the fracture reduction was completed by the robot, the translational deviation was less than 2 mm, and the angular deviation was less than 3° The autonomous reduction time was 140 s, while the master-slave reduction time was 200 s., Conclusions: Based on CT imaging verification, the accuracy of the robot in both autonomous and master-slave surgical modes meets clinical requirements. Future work will focus on further optimizing the robot system., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metabolic remodeling is a pivotal feature of cancer, with cancer stem cells frequently showcasing distinctive metabolic behaviors. Nonetheless, understanding the metabolic intricacies of triple-negative breast cancer (TNBC) and breast cancer stem cells (BCSCs) has remained elusive. In this study, we meticulously characterized the metabolic profiles of TNBC and BCSCs and delved into their potential implications for TNBC treatment. Our findings illuminated the robust lipid metabolism activity within TNBC tumors, especially in BCSCs. Furthermore, we discovered that Fabp4, through its mediation of fatty acid uptake, plays a crucial role in regulating TNBC lipid metabolism. Knocking down Fabp4 or inhibiting its activity significantly suppressed TNBC tumor progression in both the MMTV-Wnt1 spontaneous TNBC model and the TNBC patient-derived xenograft model. Mechanistically, Fabp4's influence on TNBC tumor progression was linked to its regulation of mitochondrial stability, the CPT1-mediated fatty acid oxidation process, and ROS production. Notably, in a high-fat diet model, Fabp4 deficiency proved to be a substantial inhibitor of obesity-accelerated TNBC progression. Collectively, these findings shed light on the unique metabolic patterns of TNBC and BCSCs, underscore the biological significance of Fabp4-mediated fatty acid metabolism in governing TNBC progression, and offer a solid theoretical foundation for considering metabolic interventions in breast cancer treatment. SIGNIFICANCE: Triple-negative breast cancer progression and breast cancer stem cell activity can be restricted by targeting a critical regulator of lipid responses, FABP4., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cheguo Cai reports financial support was provided by Foundation for Innovative Research Groups of the National Natural Science Foundation of China. Liya Yu reports financial support was provided by Ministry of Science and Technology of the People's Republic of China. Cheguo Cai reports financial support was provided by Fundamental Research Funds for the Central Universities. If there are other authors, they 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Valgus-varus deformity (VVD) is a common long bone deformity in broilers. Imbalance in cartilage homeostasis is the main feature of leg disease. Exosomes act as an important intercellular communication vector that regulates chondrogenesis by encapsulating specific nucleic acids and proteins. However, the exact mechanism of how plasma exosomal miRNAs regulate cartilage homeostasis in VVD broilers remains unclear. This study first demonstrated the structural disorder, growth retardation, and reduced proliferative capacity of VVD cartilage in vitro and in vivo. Subsequently, VVD and Normal broiler plasma exosomes were collected for miRNA sequencing. Cartilage-specific miR-455-5p was extraordinarily emphasized by performing bioinformatics analysis on differential miRNA target genes and further validated by tissue expression profiling. PKH67 fluorescently labeled plasma exosomes were shown to be taken up by chondrocytes, deliver miR-455-5p, inhibit chondrocyte proliferation, and disrupt their homeostasis, and these effects could be inhibited by the miR-inhibitors. Mechanistically, MiR-455-5p targets Ribosomal Protein S6 Kinase B1 (RPS6KB1) to inhibit RPS6 phosphorylation and reduce the synthesis of key proteins for cartilage proliferation, which in turn inhibits cartilage proliferation and disrupts its homeostasis. In conclusion, the present study identified abnormalities in VVD cartilage tissue and clarified the specific mechanism by which plasma exosome-derived miR-455-5p regulates cartilage homeostasis., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

In this work, the preparation of high-performance and porous regenerated cellulose (RCNH) films for seed germination application were investigated. The films were prepared from bamboo-based cellulose carbamate-NaOH/ZnO/urea and coagulated using environmentally friendly aqueous solution of (NH 4 ) 2 SO 4 . The results showed that the pore size of the films could be efficiently controlled by changing the concentration and temperature of the coagulation bath. In a mild environment, the system remains undisturbed, resulting in slow diffusion between the solvent and coagulation bath. This allows for the cellulose molecular chains to align in parallel and self-aggregate, forming a three-dimensional network structure. Therefore, the best mechanical properties were demonstrated by a film coagulated using 5 wt% (NH 4 ) 2 SO 4 solution at 10 °C. This film showed excellent tensile strength of 108 MPa and high elongation at break (35 %). As compared to a plastic wrap, the film demonstrated higher permeability for oxygen, and a moisture retaining ability. Due to these properties, it could be used as an agricultural film to encase and promote the growth of mung bean seeds. Moreover, the film was biodegradable with a short decomposition time, losing 90.75 % of its original mass after 63 days. In a summary, this work provides a route for robust, biodegradable, and permeable regenerated cellulose films with potential applications as biodegradable agricultural mulches., 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.)

Laccase is a green catalyst that can efficiently catalyze phenolic pollutants, and its catalytic efficiency is closely related to the interaction between enzyme and substrates. To investigate the binding effects between enzyme and phenolic pollutants, phenol, p-chlorophenol, and bisphenol A were used as substrates in this study. We focused on the removal and catalytic mechanism of these pollutants in water using yellow laccase derived from Coriolopsis gallica. The enzymatic catalytic products were characterized using Ultraviolet-Visible Absorption Spectroscopy (UV-Vis), Fourier Transform Infrared Spectroscopy (FTIR), and High-Resolution Mass Spectrometry (HRMS), and the catalytic mechanism of laccase on phenolic pollutants was further explored by molecular docking. Based on the structural characterization and molecular docking results, the possible polymerization pathways of these phenolic compounds were speculated. Laccase catalyzed phenol to produce phenolic hydroxyl radicals, their para-radicals, and ortho-radicals, which polymerized to form oligomers linked by benzene‑oxygen-benzene and benzene-benzene. P-chlorophenol produced phenolic hydroxyl radicals and their ortho-radicals, polymerizing to form oligomers connected by benzene‑oxygen-benzene or benzene-benzene. The CC bond of the isopropyl group of bisphenol A broke to formed an intermediate product, which was further polymerized to formed a benzene‑oxygen-benzene linked oligomer., 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.)

Background: High glucose levels are a primary cause of diabetes-associated cellular dysfunction and tissue damage. Muscles are the key insulin target organ and therefore, have a high level of sensitivity to hyperglycemia. Our previous study revealed that 20(S)-ginsenoside Rg3 (S-Rg3) is a monomer with a good myogenic differentiation effect in ginsenoside. Furthermore, it can alleviate dexamethasone-induced muscle atrophy by protecting mitochondrial function. However, whether S-Rg3 is effective for diabetic-induced muscle atrophy has not been reported., Purpose: This study aimed to investigate the protective effect of S-Rg3 on diabetic-induced muscle atrophy., Methods: C2C12 myoblasts, Drosophila, and mice were used as model systems, and the protective effect of S-Rg3 on diabetes was evaluated by assessing the levels of glucose and lipids. Furthermore, H&E, toluidine blue, Giemsa, and immunofluorescence staining were performed to detect the effects of S-Rg3 on muscle atrophy and myogenic differentiation. Moreover, the effects of S-Rg3 on mitochondrial morphology and function were also evaluated by electron microscopy, flow cytometry, and Seahorse. In addition, the underlying pathways of S-Rg3 effects were detected by Western blot. The related inhibitors and gene mutations in Drosophila were used for validation., Results: The analysis of diabetic mice model fed with a high-fat diet (HFD) and high glucose (HG) revealed that in the injured C2C12 myoblasts, S-Rg3 treatment significantly reduced the levels of triglycerides and glucose. Furthermore, it promoted the differentiation of myoblasts and inhibited mitochondrial dysfunction. In the Drosophila HG and HFD diabetic model, S-Rg3 reduced triglyceride and trehalose levels, increased climbing distance values, promoted myoblasts differentiation, preserved mitochondrial function, and inhibited muscle atrophy. Mechanistically, the beneficial effects of S-Rg3 were at least partially associated with the phosphorylation of AMPK and FoxO3 together with the inhibition of Smad3 phosphorylation, this pathway was validated by the UAS-AMPKα-RNAi Drosophila model., Conclusion: In summary, this study revealed mechanistic insights into how S-Rg3 protects against diabetes-associated muscle atrophy in cells, Drosophila, and mice., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Despite the fact that red blood cell (RBC) transfusion is commonly applied in surgical intensive care unit (ICU), the effect of RBC transfusion on long-term outcomes remains undetermined. We aimed to explore the association between RBC transfusion and the long-term prognosis of surgical sepsis survivors., Methods: This retrospective study was conducted on adult sepsis patients admitted to a tertiary surgical ICU center in China. Patients were divided into transfusion and non-transfusion groups based on the presence of RBC transfusion. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW)were performed to balance the potential confounders., Results: A total of 1421 surgical sepsis survivors were enrolled, including 403 transfused patients and 1018 non-transfused patients. There was a significant difference in 1-year mortality between the two groups (23.1 ​% vs 12.7 ​%, HR: 1.539, 95 ​% confidence interval [CI]: 1.030-2.299, P ​< ​0.001). After PSM and IPTW, transfused patients still showed significantly increased 1-year mortality risks compared to non-transfused individuals (PSM: 23.6 ​% vs 15.9 ​%, HR 1.606, 95 ​% CI 1.036-2.488 ​P ​= ​0.034; IPTW: 20.1 ​% vs 12.9 ​%, HR 1.600, 95 ​% CI 1.040-2.462 ​P ​= ​0.032). Among patients with nadir hemoglobin below 70 ​g/L, 1-year mortality risks in both groups were similar (HR 1.461, 95 ​% CI 0.909-2.348, P ​= ​0.118). However, among patients with nadir hemoglobin above 70 ​g/L, RBC transfusion was correlated with increased 1-year mortality risk (HR 1.556, 95 ​% CI 1.020-2.374, P ​= ​0.040)., Conclusion: For surgical sepsis survivors, RBC transfusion during ICU stay was associated with increased 1-year mortality, especially when patients show hemoglobin levels above 70 ​g/L., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In 2016, China introduced universal antiretroviral therapy (ART) for all HIV-infected individuals regardless of CD4 cell count. However, the natural history and rate of CD4 count decline among heterosexually-infected individuals remain uncharacterized. Analyzing national surveillance data can address this gap and shed light on the pathogenesis of HIV in this population. We used a linear mixed-effects model to assess CD4 trajectory over time before ART initiation and estimated the median time from HIV seroconversion to reaching CD4 thresholds of < 500, < 350, and < 200 cell/mm 3 . From the Chinese HIV/AIDS Comprehensive Response Information Management System, 59,085 eligible individuals were identified, with 113 having data to estimate the date of HIV seroconversion. The linear mixed-effects models estimated an intercept of 23.64 (95% confidence interval [CI]: 22.41 to 24.87) and a slope of -1.32 (95% CI: -1.34 to -1.30) for males, and an intercept of 22.70 (95% CI: 21.00 to 24.40) and a slope of -1.29 (95% CI: -1.31 to -1.27) for females. The estimated median times from HIV seroconversion to reaching CD4 count thresholds of < 500, < 350, < 200 cells/mm 3 were 0.97, 3.74, and 7.20 years for males, and 0.26, 3.09, and 6.48 years for females, respectively. Males consistently took longer to reach these CD4 count thresholds compared to females of the same age group. Older individuals (≥ 40 years) reached CD4 thresholds faster than younger individuals (15-29 years), indicating more rapid disease progression in older people living with HIV., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Titanium and its alloys are the most commonly used biometals for developing orthopedic implants to treat various forms of bone fractures and defects, but their clinical performance is still challenged by the unfavorable mechanical and biological interactions at the implant-tissue interface, which substantially impede bone healing at the defects and reduce the quality of regenerated bones. Moreover, the impaired osteogenesis capacity of patients under certain pathological conditions such as diabetes and osteoporosis may further impair the osseointegration of Ti-based implants and increase the risk of treatment failure. To address these issues, various modification strategies have been developed to regulate the implant-bone interactions for improving bone growth and remodeling in situ . In this review, we provide a comprehensive analysis on the state-of-the-art synthetic nanointerfacial bioengineering strategies for designing Ti-based biofunctional orthopedic implants, with special emphasis on the contributions to (1) promotion of new bone formation and binding at the implant-bone interface, (2) bacterial elimination for preventing peri-implant infection and (3) overcoming osseointegration resistance induced by degenerative bone diseases. Furthermore, a perspective is included to discuss the challenges and potential opportunities for the interfacial engineering of Ti implants in a translational perspective. Overall, it is envisioned that the insights in this review may guide future research in the area of biometallic orthopedic implants for improving bone repair with enhanced efficacy and safety.

Klebsiella pneumoniae, an emerging multidrug-resistant pathogen, exhibits hypermucoviscosity (HMV) as a critical virulence trait mediated by its capsular polysaccharide (CPS). Recent discoveries have determined acetylation as a significant modification for CPS, although its impact on HMV and virulence was previously unknown. This study elucidates the roles of two enzymes: Klebsiella pneumoniae Acetylated CPS Esterase (KpACE), an esterase that removes acetyl groups from CPS, and WcsU, an acetyltransferase that adds acetyl groups to CPS. KpACE is highly upregulated in an ompR-deficient mutant lacking HMV, and its overexpression consistently reduces HMV and diminishes virulence in a mouse model of pneumonia. The esterase domain-containing KpACE effectively deacetylates model sugar substrates and CPS-K2. Site-directed mutagenesis of the conserved catalytic histidine residue at position 370 significantly reduces its enzymatic activity. This reduction correlates with decreased HMV, affecting key virulence traits including biofilm formation and serum resistance. Similarly, a deficiency in the wcsU gene abolishes CPS acetylation, and reduces HMV and virulence. These results highlight the importance of the delicate balance between CPS acetylation by WcsU and deacetylation by KpACE in regulating the pathogenicity of K. pneumoniae. Understanding this balance provides new insights into the modulation of virulence traits and potential therapeutic targets for combating K. pneumoniae infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In response to growing pressure on companies to manage and improve their reputation regarding environmental, social, and governance (ESG) issues, the audit is regarded as a vital resource for ensuring ESG risk management, improving transparency, mitigating opportunistic constraints, and guaranteeing accurate reporting. The objective of this paper was to investigate the role of audit quality in improving ESG performance, as well as to examine the role of media coverage represented by ESG controversy score in moderating these relationships. We analyzed 303 Chinese companies with 2,121 observations covering the period from 2017 to 2023. The results suggest that the effects of audit quality as measured by the Big 4 and audit fee on improving ESG performance are positive but not significant. On the other hand, the results reveal that media coverage serves as a positive, albeit non-significant, moderating variable between audit quality measured by the Big 4 and ESG performance, while it has a significant negative effect when audit quality is evaluated based on audit fees. The results indicate that improving ESG performance is significantly linked to auditors intensifying their practices and implementing their work more stringently. More importantly, media coverage is an important additional driver and economic incentive that encourages companies to steer clear of poor ESG-related practices., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Emulating biological perception mechanisms to construct intelligent sensing devices and systems represents a paradigm for promoting human-computer interaction in the Internet of Everything era. Nonetheless, developing highly sensitive, real-time sensing and rapidly integrated intelligent interaction units remains a challenging and time-consuming endeavor. This study employs a low-temperature glow discharge technique to rapidly fabricate graded nanotexturing architectural triboelectric nanopaper, upon which wearable triboelectric sensors for real-time tactile detection are designed. The structure enhances the contact area under an external force. Additionally, the Z-stacking structure design enables the sensor to achieve a remarkable sensitivity of 10.3 kPa -1 and a rapid response time of 52 ms. Furthermore, a tactile sensor array was designed to demonstrate the triboelectric sensor's ability to recognize characteristic pressures. With programmable machine learning techniques, the object recognition rate reached 97%. This study supports material structural design across disciplines, laying a solid foundation for the rapid fabrication and integration of transient wearable electronics.

Effective treatment of myocardial ischemia-reperfusion (MIR) injury remains an unmet clinical need. Cardiomyocyte apoptosis is common at this stage and poses a significant risk. Corylin, a flavonoid compound extracted from Psoralea corylifolia L., has been shown to have anti-inflammatory, anticancer, and antiatherosclerotic properties. However, whether and how corylin affects MIR injury remain unclear. In this study, we explored the mechanism of corylin as a potent therapeutic agent for MI/R injury, using a left anterior descending (LAD) coronary artery ligation and oxygen-glucose deprivation and reperfusion (OGD/R) model in vivo and in vitro. TUNEL, Annexin-V/PI double staining,Ki67 immunohistochemistry, western blot analysis, and immunofluorescence were used to validate cell apoptosis level and Raf-1/ASK1 complex activity. The interaction between corylin and Raf-1/ASK1 complex was detected using molecular docking, corylin-Raf-1 binding assays, and coimmunoprecipitation (Co-IP). Moreover, TTC staining, echocardiography, HE staining, Masson trichrome staining and serological testing were performed to assess the cardioprotective effects of corylin in vivo. These findings showed that corylin reduces MIR injury-induced cardiomyocyte apoptosis and improves cardiac function. Mechanistically, corylin can interact with Raf-1 and promote the formation of the Raf-1/ASK1 complex, thus inhibiting cardiomyocyte apoptosis. In conclusion, our results demonstrate that corylin ameliorated cardiac dysfunction after MIR injury by reducing myocardial apoptosis., 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.)

Constructing efficient electrocatalysts for the oxygen reduction reaction (ORR) is crucial for the commercialization of metal-air batteries. Iron oxide-based catalysts exhibit promising potential for ORR. However, addressing the issue of inferior catalytic performance is essential, and a comprehensive understanding of the catalytic mechanism of iron oxide-based catalysts is also lacking. In this study, we present Fe 3 O 4 nanoparticles encapsulated in N-doped graphitic carbon layers (NGC) hosted by hierarchically porous carbon (Fe 3 O 4 @NGC), achieved through a facile dual melt-salt template strategy. The encapsulation of Fe 3 O 4 nanoparticles protects them from corrosion and exfoliation, endowing the catalysts with superior stability. Density functional theory (DFT) calculations discover that the electronic interaction between Fe 3 O 4 nanoparticles and N-doped graphitic carbon layers induces directional interfacial electron transfer, which effectively modulates the surface electronic structure to improve the binding ability to O 2 , weaken the OO bond, and optimize the adsorption of intermediates, thus boosting the intrinsic activity. DFT unveils that the C atoms nearest to graphitic-N in NGC are active sites. Finally, the synergistic effects of Fe 3 O 4 nanoparticles and NGC result in outstanding ORR performance and superior stability and methanol tolerance of Fe 3 O 4 @NGC, with a half-wave potential of 0.89 V, surpassing that of Pt/C by 50 mV. Fe 3 O 4 @NGC also shows better performance than Pt/C when used as the air-electrode catalyst in zinc-air battery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung cancer (NSCLC)., Methods: This multicenter, open-label, phase 1b study comprising dose-confirmation and dose-expansion parts investigated the combination of spartalizumab and various PDC regimens, with or without canakinumab, in treatment-naïve patients with PD-L1-unselected, metastatic NSCLC. The primary objectives were to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of spartalizumab, with or without canakinumab, in combination with PDC in the dose-confirmation part and antitumor activity of spartalizumab in the dose-expansion part., Results: The MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m 2 )/cisplatin (75 mg/m 2 ) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m 2 )/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m 2 )/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis). The RDE of canakinumab combined with spartalizumab and pemetrexed/cisplatin (group E; no DLTs) was 200 mg Q3W (no dose-expansion part was initiated). No new safety signals were identified. In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2-7.5 months), overall survival (29.7 months vs. 16.1-21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months)., Conclusions: The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin., Trial Registration: The trial was registered in Clinicaltrials.gov with identifier no. NCT03064854. Date of Registration: 06 February 2017., (© 2024. The Author(s).)

The purpose of this study is to investigate the influencing factors of abnormal pulmonary ventilation function in occupational exposed populations and to establish a risk prediction model. The findings will provide a basis for formulating corresponding strategies for the prevention and treatment of occupational diseases. The study focused on workers who underwent occupational health examinations in the year 2020. Statistical analysis was conducted using methods such as t-tests, chi-square tests, and multiple logistic regression analysis. Additionally, machine learning methods were employed to establish multiple models to address classification problems. Among the 7472 workers who participated in the occupational health examination, 1681 cases of abnormal pulmonary ventilation function were detected, resulting in a detection rate of 22.6%. Based on the analysis of occupational hazard data, a risk prediction model was established. Age, work tenure, type of the employing enterprise, and type of dust exposure are all identified as driving factors for abnormal pulmonary function. These factors were used as predictive variables for establishing the risk prediction model. Among the various models evaluated, the logistic regression model was found to be the optimal model for predicting abnormal pulmonary ventilation function., (© 2024. The Author(s).)

Iron carbodiimide (FeNCN) often suffers from unstable interfacial structure with an unexpected failure of Na-ion storage performance. In this work, Co 3 O 4 particles were deposited on the surface of FeNCN. This Co 3 O 4 nanolayer led to the formation of a Na 2 CO 3 -rich inorganic component SEI film to enhance the stability of a promoted-loading FeNCN electrode interface with fast Na + migration pathway. Benefitting from this strategy, the FeNCN electrode could present a capacity retention rate of 99.95% per cycle after 1500 cycles at 1 A g -1 . The design of interfacial structure in a promoted-loading electrode could be a reference for stable and high-rate performance of carbodiimide-based materials.

Background: Large-diameter titanium dioxide nanotubes (TNTs) have shown promise in preserving osteoblast function under oxidative stress (OS) in vitro. However, their ability to enhance osteogenesis in vivo under OS conditions and the underlying mechanisms remain unclear., Purpose: This study aimed to evaluate the osteogenic potential of 110 nm TNTs (TNT110) compared to 30 nm TNTs (TNT30) in an aging rat model exhibiting OS, and to investigate the mechanisms involved., Methods: Surface properties of TNTs were characterized, and in vitro and in vivo experiments were conducted to assess their osteoinductive effects under OS. Transcriptomic, proteomic analyses, and Western blotting were performed to investigate the protective mechanisms of TNT110 on osteoblasts. Protein adsorption studies focused on the roles of fibronectin (FN) and albumin (BSA) in modulating osteoblast behavior on TNT110., Results: In both in vitro and in vivo experiments, TNT110 significantly improved new bone formation and supported osteoblast survival under OS conditions. Subsequent ribonucleic acid sequencing results indicated that TNT110 tended to attenuate inflammatory responses and reactive oxygen species (ROS) expression while promoting endoplasmic reticulum (ER) stress and extracellular matrix receptor interactions, all of which are crucial for osteoblast survival and functionality. Further confirmation indicated that the cellular behavior changes of osteoblasts in the TNT110 group could only occur in the presence of serum. Moreover, proteomic analysis under OS conditions revealed the pivotal roles of FN and BSA in augmenting TNT110's resistance to OS. Surface pretreatment of TNT110 with FN/BSA alone could beneficially influence the early adhesion, spreading, ER activity, and ROS expression of osteoblasts, a trend not observed with TNT30., Conclusion: TNT110 effectively protects osteoblast function in the OS microenvironment by modulating protein adsorption, with FN and BSA synergistically enhancing osteogenesis. These findings suggest TNT110's potential for use in implants for elderly patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Xiang et al.)

Fenofibrate is a clinically prescribed drug for treating hypertriglyceridemia, which is also a classic peroxisome proliferator-activated receptor α (PPARα) agonist. We previously reported that fenofibrate induced liver enlargement in adult mice partially through activation of the yes-associated protein (YAP) signaling pathway. However, the effects of fenofibrate on liver enlargement and the YAP signaling pathway in aging mice remain unclear. In this study, D-galactose-induced aging mice, naturally aging mice, and senescence-accelerated mice P8 (SAMP8) were used to investigate the effects of aging on fenofibrate-induced liver enlargement and YAP signaling activation. The results showed that fenofibrate-induced liver enlargement in aging mice was consistent with that of adult mice. The effects of fenofibrate on hepatocyte enlargement around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area were comparable between adult and aging mice. There was no significant difference in the upregulation of PPARα downstream proteins between the two groups following fenofibrate treatment. Fenofibrate treatment also increased the expression of proliferation-related proteins and activated the YAP signaling pathway to a similar degree in both groups. In summary, these results demonstrate that the fenofibrate-induced liver enlargement and activation of the YAP pathway are consistent between adult and aging mice, indicating that the effects of fenofibrate on promoting liver enlargement and its activation of the PPARα and YAP pathway were independent of aging. These findings offer a new perspective for the clinical use of fenofibrate in elderly patients and provide a new insight for the role of PPARα in liver enlargement., 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.)

Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits., (© 2024. The Author(s).)

The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal development. Although the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been extensively studied, the influence of neural signals, particularly those from the sympathetic nervous system, remains poorly understood. Here, using a mouse mammary gland model, we delved into the regulatory role of sympathetic nervous signaling in the context of mammary stem cells and mammary development. Our findings revealed that depletion of sympathetic nerve signals results in defective mammary development during puberty, adulthood, and pregnancy, accompanied by a reduction in mammary stem cell numbers. Through in vitro three-dimensional culture and in vivo transplantation analyses, we demonstrated that the absence of sympathetic nerve signals hinders mammary stem cell self-renewal and regeneration, while activation of sympathetic nervous signaling promotes these capacities. Mechanistically, sympathetic nerve signals orchestrate mammary stem cell activity and mammary development through the extracellular signal-regulated kinase signaling pathway. Collectively, our study unveils the crucial roles of sympathetic nerve signals in sustaining mammary development and regulating mammary stem cell activity, offering a novel perspective on the involvement of the nervous system in modulating adult stem cell function and organ development., (© The Author(s) (2024). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Objective: ACAN gene variants, prevalent monogenic defects linked to short stature, are characterized by impaired cartilage generation in growth plates. We aimed to unravel the genetic basis of short stature in a specific pedigree by investigating the role of a novel non-canonical splicing-site variant, c.630-13G > A, within the ACAN gene., Method: Sanger sequencing was used for pedigree verification, and the effects of this variant on mRNA splicing were analyzed through minigene assay., Results: The study revealed that this variant led to the creation of a previously unreported splice site in the fourth intron, resulting in the incorporation of an 11 bp sequence from the intron into the final transcript. This alteration led to a frameshift and formation of a premature termination codon, impacting the structure of the aggrecan protein., Conclusions: We document the pathogenicity of an ACAN non-canonical splicing-site variant, emphasizing the significance of considering intronic variants during genetic testing., 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.)

Computer-vision and machine-learning (ML) approaches are being developed to provide scalable, unbiased, and sensitive methods to assess mouse behavior. Here, we used the ML-based variational animal motion embedding (VAME) segmentation platform to assess spontaneous behavior in humanized App knockin and transgenic APP models of Alzheimer's disease (AD) and to test the role of AD-related neuroinflammation in these behavioral manifestations. We found marked alterations in spontaneous behavior in App NL-G-F and 5xFAD mice, including age-dependent changes in motif utilization, disorganized behavioral sequences, increased transitions, and randomness. Notably, blocking fibrinogen-microglia interactions in 5xFAD-Fgg γ390-396A mice largely prevented spontaneous behavioral alterations, indicating a key role for neuroinflammation. Thus, AD-related spontaneous behavioral alterations are prominent in knockin and transgenic models and sensitive to therapeutic interventions. VAME outcomes had higher specificity and sensitivity than conventional behavioral outcomes. We conclude that spontaneous behavior effectively captures age- and sex-dependent disease manifestations and treatment efficacy in AD models., Competing Interests: Declaration of interests K.A. is the scientific founder, advisor, and shareholder of Therini Bio; her conflicts of interests are managed by the Gladstone Institutes. K.L. is currently an employee of REWE Group (Germany). P.B. is currently an employee of Telekom (Germany)., (Copyright © 2024. Published by Elsevier Inc.)