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Global Net Anthropogenic Nitrogen Input (NANI) at high resolution is crucial for assessing the impact of human activities on aquatic environments. Insufficient global high-resolution data sources and methods have hindered the effective examination of the global characteristics and driving forces of NANI. This study presents a general framework for calculating global NANI, providing estimates at a 5-arc-minute resolution and over 1.42 million lake basins in 2015. The results highlight the region near the Tropic of Cancer as a concentration area for high NANI and an inflection point for latitude-based accumulation variation. It also emphasizes the uneven distribution of NANI among continents, with Asia and Africa having the highest proportions, yet their high and low values are notably lower than those of Europe and South America. A similar pattern is observed in global lakes, where Asia has the smallest quantity and volume, but the highest NANI intensity. In contrast, North America and Europe have larger quantities and volumes but the lowest NANI intensity. The global distribution characteristics reveal a clustering pattern in high and low values, with 1.25 % of the area having a sum of NANI exceeding 20 %. The uncertainty analysis regarding model parameters indicates that continents with the highest NANI do not always exhibit the highest uncertainty. These results bridge the gap between global nitrogen sustainable management and anthropogenic nitrogen input. They support research on spatiotemporal changes and controlling factors of global river nutrient loads, as well as the impact of climatic factors on basin nitrogen loss and its variability., 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: Nucleic acid extraction (NAE) is essential in molecular diagnostics, genetic engineering, and DNA sequencing. While advances in switching valve-assisted, self-contained microfluidic (S 2 M) cartridges have improved the NAE processes, challenges persist in streamlining workflows, reducing processing times, and enhancing multi-target detection. Achieving these objectives requires precise control of on-chip fluid dynamics and efficient transfer of nucleic acid solutions (NAS) to detection areas. However, research on novel S 2 M cartridge designs and compatible fluid control systems is still limited., Result: This study presented an innovative NAE system that integrated an S 2 M cartridge, a constant pressure (CP) pump, a metal heating bath, a rotating lever, and a magnet. The S 2 M cartridge contained the reagents for both NAE and detection, while the CP pump provided stable, precise, and rapid fluid delivery, outperforming traditional peristaltic and injection pumps, especially for handling small volumes and reducing pulsation. A custom rotating lever connects reagent chambers, facilitating mixing, cleaning, elution, and NAS transfer. This system showed advantages over manual methods, achieving all processes in 20 min. The CP pump-assisted S 2 M cartridge enabled rapid MBs re-suspension with a recovery rate of 80 %. The system's sensitivity, repeatability, and ease of use were also confirmed. The NAE system can extract Escherichia coli DNA (50 CFU mL^-1) from food and serum samples and viral DNA (HBV, HCV, HIV) at 200 copies mL^-1 from serum samples., Significance: This study highlighted the need for an efficient fluid system in the S 2 M cartridge for stable NAE. By streamlining NAE and facilitating on-chip reagent preparation, the system enhanced point-of-care diagnostics. Although manual steps remain, the CP pump effectively managed fluid processes, paving the way for automated pathogen detection. Moreover, when combined with visual detection reagents, the NAE system showed promise as a direct molecular diagnostic tool., 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.)

Red mud and phosphogypsum are two of the most typical bulk industrial solid wastes. How they can be efficiently recycled as resources on a large scale and at low costs has always been a global issue that urgently needs to be solved. By constructing a small-scale test site and preparing two types of artificial soils using red mud and phosphogypsum, this study simulated their engineering applications in vegetation restoration and ecological reconstruction. According to the results of this study, the artificial soils contained a series of major elements (e.g. O, Si, Al, Fe, Ca, Na, K, and Mg) similar to those in common natural soil, and preliminarily possessed basic physicochemical properties (pH, moisture, organic matter, and cation exchange capacity), main nutrient conditions (nitrogen, phosphorus and potassium), and biochemical characteristics that could meet the demands of plant growth. A total of 18 different types of adaptable plants (e.g. wood, herbs, flowers, succulents, etc) grew in the test sites, indicating that the artificial soils could be used for vegetation greening and landscaping. The preliminary formation of microbial (fungal and bacterial) community diversity and the gradually enriched arthropod community diversity reflected the constantly improving quality of the artificial soils, suggesting that they could be used for the gradual construction of artificial soil micro-ecosystems. Overall, the artificial soils provided a feasible solution for the large-scale, low-cost, and highly efficient synergistic disposal of red mud and phosphogypsum, with enormous potential for future engineering applications. They are expected to be used for vegetation greening, landscaping, and ecological environment improvement in tailings, collapse, and soil-deficient areas, as well as along municipal roads., 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.)

The relationship between serum uric acid (SUA) and mortality in patients with cardiovascular disease (CVD) remains controversial. We aimed to explore the relationship between SUA and all-cause mortality (ACM) and cardiovascular mortality (CVM) in adult patients with CVD. This cohort study included 3977 patients with CVD from the National Health and Nutrition Examination Survey (2005-2018). Death outcomes were determined by linking National Death Index (NDI) records through December 31, 2019. We explored the association of SUA with mortality using weighted Cox proportional hazards regression models, subgroup analysis, Kaplan-Meier survival curves, weighted restricted cubic spline (RCS) models, and weighted threshold effect analysis among patients with CVD. During a median follow-up of 68 months (interquartile range, 34-110 months), 1,360 (34.2%) of the 3,977 patients with cardiovascular disease died, of which 536 (13.5%) died of cardiovascular deaths and 824 (20.7%) died of non-cardiovascular deaths. In a multivariable-adjusted model (Model 3), the risk of ACM (HR 1.38, 95% CI 1.16-1.64) and the risk of CVM (HR 1.39, 95% CI 1.04-1.86) for participants in the SUA Q4 group were significantly higher. In patients with CVD, RCS regression analysis revealed a nonlinear association (p < 0.001 for all nonlinearities) between SUA, ACM, and CVM in the overall population and in men. Subgroup analysis showed a nonlinear association between ACM and CVM with SUA in patients with CVD combined with chronic kidney disease (CKD), with thresholds of 5.49 and 5.64, respectively. Time-dependent ROC curves indicated areas under the curve of 0.61, 0.60, 0.58, and 0.55 for 1-, 3-, 5-, and 10-year survival for ACM and 0.69, 0.61, 0.59, and 0.56 for CVM, respectively. We demonstrate that SUA is an independent prognostic factor for the risk of ACM and CVM in patients with CVD, supporting a U-shaped association between SUA and mortality, with thresholds of 5.49 and 5.64, respectively. In patients with CVD combined with CKD, the association of the ACM and the CVM with SUA remains nonlinear., (© 2024. The Author(s).)

Background: New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH., Methods: The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features., Results: T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression., Conclusions: Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores., (© 2024. The Author(s).)

Background/ Aims: The lack of context for anterior segment optical coherence tomography (ASOCT) measurements impedes its clinical utility. We established the normative distribution of anterior chamber depth (ACD), area (ACA) and width (ACW) and lens vault (LV), and applied percentile cut-offs to detect primary angle closure disease (PACD; ≥180° posterior trabecular meshwork occluded)., Methods: We included subjects from the Singapore Chinese Eye Study with ASOCT scans. Eyes with ocular surgery or laser procedures, and ocular trauma were excluded. A deep-learning algorithm was used to obtain Visante ASOCT (Carl Zeiss Meditec, USA) measurements. Normative distribution was established using 80% of eyes with open angles. Multivariable logistic regression was performed on 80% open and 80% angle closure eyes. Diagnostic performance was evaluated using 20% open and 20% angle closure eyes., Results: We included 2157 eyes (1853 open angles; 304 angle closure) for analysis. ACD, ACA and ACW decreased with age and were smaller in females, and vice versa for LV (all p<0.022). ACD 20th percentile and LV 85th percentile had a balanced accuracy of 84.4% and 84.2% in detecting PACD, respectively. When combined, ACD 20th and LV 85th percentile had 88.68% sensitivity and 88.85% specificity in detecting PACD as compared with a multivariable regression model (ACA, angle opening distance, LV, iris area) with 88.33% sensitivity and 83.75% specificity., Conclusion: Anterior chamber parameters varied with age and gender. The ACD 20th and LV 85th percentile values may be used in silos or in combination to detect PACD in the absence of more sophisticated classification algorithms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

An approach to suppressing Brillouin scattering-induced noise in long-haul high-power radio-over-fiber (RoF) links is proposed via non-uniformly distributed four-tone phase modulation. Four single-tone signals with uneven frequency intervals are utilized to phase modulate the optical signal before transmission. The power transferring from the optical carrier to the non-uniformly distributed modulation sidebands largely suppresses the Brillouin scattering-induced relative intensity noise (RIN). In the experiment, transmission of a 64-QAM wireless communication signal centered at 10 GHz and with a bandwidth of 100 MHz is demonstrated. The threshold of the stimulated Brillouin scattering (SBS) in a high-power RoF link involving a spool of a single-mode fiber (SMF) with a length of 20.5 km is increased by 11 dB based on this scheme, compared with that without phase modulation. Under an input optical power of 19 dBm, the error vector magnitude (EVM) and the adjacent channel leakage ratio (ACLR) are optimized from 34.39% to 1.32% and from -20.73 dBc to -35.32 dBc, without and with phase modulation, respectively. This scheme paves a way to realizing long-haul high-power RoF links for efficiently transmitting broadband wireless communication signals in cloud radio access networks (C-RANs).

A temporal dissipative soliton (TDS) with controllable morphology is demonstrated in a time-delayed coupled optoelectronic oscillator (OEO) driven by two optical carriers with different wavelengths. The morphology of the TDS is controlled by the power difference between the two optical carriers and the delay difference induced by the group-velocity dispersion (GVD) in the OEO loop. When the delay difference is small, the OEO operates in a single-soliton state. With the increase of the wavelength interval between the two optical carriers, the delay difference becomes significant so that various compound TDS structures are observed, where the TDS interval is equal to the delay difference. The morphology of the compound TDSs can be switched between a pulsating TDS packet and a stable compound TDS structure by further tuning the power difference between the two optical carriers. This discovery not only facilitates the investigation of novel soliton dynamics but also provides a method for generating customized pulse waveforms.

Saline lakes, characterized by high salinity and limited nutrient availability, provide an ideal environment for studying extreme halophiles and their biogeochemical processes. The present study examined prokaryotic microbial communities and their ecological functions in lentic sediments (with the salinity gradient and time series) using 16S rRNA amplicon sequencing and a metagenomic approach. Our findings revealed a negative correlation between microbial diversity and salinity. The notable predominance of Archaea in high-salinity lakes signified a considerable alteration in the composition of the microbial community. The results indicate that elevated salinity promotes homogeneous selection pressures, causing substantial alterations in microbial diversity and community structure, and simultaneously hindering interactions among microorganisms. This results in a notable decrease in the complexity of microbial ecological networks, ultimately influencing the overall ecological functional responses of microbial communities such as carbon fixation, sulfur, and nitrogen metabolism. Overall, our findings reveal salinity drives a notable predominance of Archaea, selects for species adapted to extreme conditions, and decreases microbial community complexity within saline lake ecosystems., (© 2024. The Author(s).)

Background: Esophageal cancer poses a significant health burden globally. Endoscopic treatment has emerged as a viable option for patient ineligible for surgery or experiencing disease recurrence post-radiotherapy., Methods: Patients visiting the Department of Endoscopy at the Cancer Hospital of China Academy of Medical Sciences between March 2009 and March 2024 were retrospectively analyzed. Inclusion criteria encompassed patients with histologically confirmed esophageal cancer who had not undergone surgery, but received radiotherapy or CRT, and subsequently opted for endoscopic treatment. Data on demographics, treatment modalities, recurrence patterns, histopathological characteristics, and outcomes were collected. Statistical analysis was conducted using SPSS 27.0, employing Kolmogorov-Smirnov tests for data normality assessment., Results: Out of 25 included patients, the mean age was 60.29 years, with a predominance of males (88%). Most patients (64%) received chemoradiotherapy (CRT), while the rest underwent radiotherapy alone. The median follow-up duration was 50.92 months, with a median recurrence time of 38.92 months. Majority (56%) presented with a solitary lesion and 76% had negative margins. Histopathological analysis revealed various stages of cancer, with the most common being high-grade squamous epithelial neoplasia (64%). Survival analysis indicated a 72% overall survival rate, with 16% surviving beyond 5-year post-treatment. Approximately, 20% succumbed during the study, primarily due to non-esophageal causes (16%)., Conclusion: Endoscopic treatment shows promise as a therapeutic option for selected esophageal cancer patients, offering favorable outcomes in terms of survival and disease control. Further prospective studies are warranted to validate these findings and optimize patient selection criteria for endoscopic interventions in esophageal cancer management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ocean acidification (OA) can affect marine bivalves at various levels of biological organization. Yet, little effort has been devoted to understanding how OA affects the reproductive events of marine bivalves during multiple cycles of maturation. Here, we tested sex-specific reproductive responses of Manila clams (Ruditapes philippinarum) to OA during gonadal rematuration. Under acidified conditions, both male and female clams exhibited delayed gonadal rematuration following spawning and impairments in gonadal tissues, which can be likely ascribed to lowered concentrations of hormones and vitellogenin. The findings indicate that marine bivalves experience significant declines in reproductive capacity as a result of OA during their reproductive cycles, with clear sex-specific differences. Consequently, it is essential to consider sex-specific reproduction responses of marine bivalves to OA when developing conservation strategies and forecasting population sustainability in a rapidly acidifying marine environment., 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.)

Darolutamide is a potent second-generation, selective nonsteroidal androgen receptor inhibitor (ARI), which has been approved by the US Food and Drug Administration (FDA) in treating castrate-resistant, non-metastatic prostate cancer (nmCRPC). Whether darolutamide affects the activity of UDP-glucuronosyltransferases (UGTs) is unknown. The purpose of the present study is to evaluate the inhibitory effect of darolutamide on recombinant human UGTs and pooled human liver microsomes (HLMs), and explore the potential for drug-drug interactions (DDIs) mediated by darolutamide through UGTs inhibition. The product formation rate of UGTs substrates with or without darolutamide was determined by HPLC or UPLC-MS/MS to estimate the inhibitory effect and inhibition modes of darolutamide on UGTs were evaluated by using the inhibition kinetics experiments. The results showed that 100 μM darolutamide exhibited inhibitory effects on most of the 12 UGTs tested. Inhibition kinetic studies of the enzyme revealed that darolutamide noncompetitively inhibited UGT1A1 and competitively inhibited UGT1A7 and 2B15, with the K i of 14.75 ± 0.78 μM, 14.05 ± 0.42 μM, and 6.60 ± 0.08 μM, respectively. In particular, it also potently inhibited SN-38, the active metabolite of irinotecan, glucuronidation in HLMs with an IC 50 value of 3.84 ± 0.46 μM. In addition, the in vitro-in vivo extrapolation (IVIVE) method was used to quantitatively predict the risk of darolutamide-mediated DDI via inhibiting UGTs. The prediction results showed that darolutamide may increase the risk of DDIs when administered in combination with substrates of UGT1A1, UGT1A7, or UGT2B15. Therefore, the combined administration of darolutamide and drugs metabolized by the above UGTs should be used with caution to avoid the occurrence of potential DDIs., 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.)

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca 2+ -crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice., 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.)

Ionizing radiation (IR)-induced intestinal injury remains a major limiting factor in abdominal radiation therapy, and its pathogenesis remains unclear. In this study, mouse models of IR-induced intestinal injury were established, and the effect of IR on nuclear factor erythroid 2-related factor 2 (Nrf2) was determined. More severe IR-induced intestinal damage was observed in Nrf2 knockout (KO) mice than in wild-type mice. Then, the negative regulation of cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) signaling by Nrf2 was examined both in vivo and in vitro after IR. This was accompanied by alterations in the intestinal neutrophil and macrophage populations in mice. Subsequently, the effect of the cGAS/STING pathway on the intestinal toxicity of IR was also investigated. Moreover, the downregulation of cGAS/STING by Nrf2 via its target gene, Pirin, was confirmed using transfection assays. A rescue experiment with Pirin was also conducted using adeno-associated virus in Nrf2 KO mice. Finally, the protective effect of calcitriol against IR-induced intestinal injury, along with increased Nrf2 and Pirin levels and decreased cGAS, pSTING, and interferon-beta levels, were observed. Taken together, our results suggest that Nrf2 alleviates IR-induced intestinal injury through Pirin-mediated inhibition of the innate immunity-related cGAS/STING pathway., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Acute kidney injury (AKI) is associated with increased mortality in critically ill patients. Due to differences in the etiology and pathophysiological mechanism, the current AKI criteria put it an embarrassment to evaluate clinical therapy and prognosis., Objective: We aimed to identify subphenotypes based on routinely collected clinical data to expose the unique pathophysiologic patterns., Methods: A retrospective study was conducted based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD), and a deep clustering approach was conducted to derive subphenotypes. We conducted further analysis to uncover the underlying clinical patterns and interpret the subphenotype derivation., Results: We studied 14,189 and 19,382 patients with AKI within 48 h of ICU admission in the two datasets, respectively. Through our approach, we identified seven distinct AKI subphenotypes with mortality heterogeneity in each cohort. These subphenotypes displayed significant variations in demographics, comorbidities, levels of laboratory measurements, and survival patterns. Notably, the subphenotypes could not be effectively characterized using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria alone. Therefore, we uncovered the unique underlying characteristics of each subphenotype through model-based interpretation. To assess the usability of the subphenotypes, we conducted an evaluation, which yielded a micro-Area Under the Receiver Operating Characteristic (AUROC) of 0.81 in the single-center cohort and 0.83 in the multi-center cohort within 48-hour of admission., Conclusion: We derived highly characteristic, interpretable, and usable AKI subphenotypes that exhibited superior prognostic values., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

This work addresses the challenge of democratizing advanced Large Language Models (LLMs) by compressing their mathematical reasoning capabilities into sub-billion parameter Small Language Models (SLMs) without compromising performance. We introduce Equation-of-Thought Distillation (EoTD), a novel technique that encapsulates the reasoning process into equation-based representations to construct an EoTD dataset for fine-tuning SLMs. Additionally, we propose the Ensemble Thoughts Distillation (ETD) framework to enhance the reasoning performance of SLMs. This involves creating a reasoning dataset with multiple thought processes, including Chain-of-Thought (CoT), Program-of-Thought (PoT), and Equation-of-Thought (EoT), and using it for fine-tuning. Our experimental performance demonstrates that EoTD significantly boosts the reasoning abilities of SLMs, while ETD enables these models to achieve state-of-the-art reasoning performance., 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.)

Twelve compounds, including eleven bisabolane-type sesquiterpenoids ( 1  -  11 ), and one bacillibactin ( 12 ) were identified from marine-derived fungus Aspergillus sydowii SCSIO 41041 isolated from Creseis acicula . The chemical structures were elucidated by the basis of spectroscopic evidences, including HRESIMS, NMR and optical rotation. Biologically, all compounds were evaluated for their acetyl cholin-esterase (AChE) enzyme, pancreatic lipase (PL) enzyme, neuraminidase (NA) and phosphodiesterase 4 (PDE4) inhibitory activities. Compound 12 displayed significant inhibitory activity against neuraminidase (NA) with an IC 50 value of 24.0 μM, which was equivalent to the positive drug oseltamivir phosphate (IC 50 value of 20.0 μM). And the NA inhibitory activity was confirmed by molecular docking analysis.

Objective: To describe the association between preoperative ictal scalp electroencephalogram (EEG) results and surgical outcomes in patients with focal epilepsies., Methods: The data of consecutive patients with focal epilepsies who received surgical treatments at our center from January 2012 to December 2021 were retrospectively analyzed., Results: Our data showed that 44.2% (322/729) of patients had ictal EEG recorded on video EEG monitoring during preoperative evaluation, of which 60.6% (195/322) had a concordant ictal EEG results. No significant difference of surgery outcomes between patients with and without ictal EEG was discovered. Among MRI-negative patients, those with concordant ictal EEG had a significantly better outcome than those without ictal EEG (75.7% vs. 43.8%, p = 0.024). Further logistic regression analysis showed that concordant ictal EEG was an independent predictor for a favorable outcome (OR = 4.430, 95%CI 1.175-16.694, p = 0.028). Among MRI-positive patients, those with extra-temporal lesions and discordant ictal EEG results had a worse outcome compared to those without an ictal EEG result (44.7% vs. 68.8%, p = 0.005). Further logistic regression analysis showed that discordant ictal EEG was an independent predictor of worse outcome (OR = 0.387, 95%CI 0.186-0.807, p = 0.011) in these patients. Furthermore, our data indicated that the number of seizures was not associated with the concordance rates of the ictal EEG, nor the surgical outcomes., Conclusions: The value of ictal scalp EEG for epilepsy surgery varies widely among patients. A concordant ictal EEG predicts a good surgical outcome in MRI-negative patients, whereas a discordant ictal EEG predicts a poor postoperative outcome in lesional extratemporal lobe epilepsy., (© 2024. Fondazione Società Italiana di Neurologia.)

Carbapenems and colistin are vital antimicrobials used to treat Enterobacteriaceae-caused infections. The present study aimed to characterize the coexistence mechanism of carbapenem and colistin resistance in an Escherichia coli isolated from retail chicken meat. A total of 4 E. coli isolates co-harboring carbapenem resistance gene bla NDM (2 E. coli isolates with bla NDM-5 and 2 with bla NDM-9 ) and colistin resistance gene mcr-1. Antimicrobial susceptibility testing exhibited that all the 4 E. coli strains had multidrug resistance profile and consistent with the resistance genes they carried. MLST showed that 3 E. coli isolates belonged to a pathogenic E. coli lineage ST354, which is closely associated with human infections and pose a serious threat to public health. Whole genome sequencing (WGS) showed that 4 mcr-1-positive plasmids with sizes of 60.4 kb to 67.4 kb all belonged to the IncI2 type. A total of 5 bla NDM -harboring plasmids ranged from 99.0 kb to 138.3 kb, among which 4 plasmids belonged to unknow type and only pCS5L-NDM belonged to IncFIA/IncFIB group of hybrid plasmids, a novel carrier for bla NDM . Comparative analysis exhibited that the mcr-1 or bla NDM -carrying plasmids of E. coli strains from chicken meat showed high identity with that from Enterobacteriaceae of human origin, which indicated the risk of mcr-1 or bla NDM dissemination from retail meat to human. The simultaneous occurrence of mcr-1 and bla NDM in E. coli emphasizes the significant of antimicrobial resistance surveillance in retail meat., Competing Interests: DISCLOSURES The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68  Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate., Purpose: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods., Methods: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy ( 99 Tc m -OCT) and 68 gallium-DOTA-TATE-positron emission tomography/computed tomography ( 68  Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center., Results: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (β-CTX) levels than the normal range. The sensitivity of 68  Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99 Tc m -OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis., Conclusion: 68  Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients., (© 2024. The Author(s).)

Binary neural network (BNN) converts full-precision weights and activations into their extreme 1-bit counterparts, making it particularly suitable for deployment on lightweight mobile devices. While BNNs are typically formulated as a constrained optimization problem and optimized in the binarized space, general neural networks are formulated as an unconstrained optimization problem and optimized in the continuous space. This article introduces the hyperbolic BNN (HBNN) by leveraging the framework of hyperbolic geometry to optimize the constrained problem. Specifically, we transform the constrained problem in hyperbolic space into an unconstrained one in Euclidean space using the Riemannian exponential map. On the other hand, we also propose the exponential parametrization cluster (EPC) method, which, compared with the Riemannian exponential map, shrinks the segment domain based on a diffeomorphism. This approach increases the probability of weight flips, thereby maximizing the information gain in BNNs. Experimental results on CIFAR10, CIFAR100, and ImageNet classification datasets with VGGsmall, ResNet18, and ResNet34 models illustrate the superior performance of our HBNN over state-of-the-art methods.

Endoplasmic reticulum stress (ERS) plays crucial roles in maintaining regulatory T cells (Treg) stability and function, yet the underlying mechanism remains largely unexplored. Here we demonstrate that ERS-related protein transmembrane p24 trafficking protein 4 (TMED4) Treg-specific knockout (Tmed4ΔTreg) mice contain more Treg cells with impaired Foxp3 stability, Treg signature and suppressive activity, which leads to T cell hyperactivation, exacerbated inflammatory phenotype and boosted anti-tumor immunity in mice. Mechanistically, loss of Tmed4 causes defects in ERS and nuclear factor erythroid 2-related factor 2 (NRF2)-related antioxidant response, which results in excessive reactive oxygen species (ROS) that reduces Foxp3 stability and suppressive function of Treg cells in an IRE1α-XBP1 axis-dependent manner. The abnormalities can be effectively rescued by ROS scavenger, NRF2 inducer or forcible expression of IRE1α. Moreover, TMED4 suppresses IRE1α proteosome degradation via the ER-associated degradation (ERAD) system including BIP. Our study reveals that TMED4 maintains Treg cell stability and suppressive function through IRE1α-dependent ROS and the NRF2-related antioxidant response.

Tumor cell death induced by "cuproptosis" is a novel form of tumor death that differs from apoptosis induced by chemotherapy. It is expected to emerge as a new approach for cancer treatment. In this study, our focus was on exploiting the characteristic of "cuproptosis" which necessitates increased aerobic respiration to induce tumor cell death. To achieve this, we developed a novel drug delivery system using a CaCO 3 @CuO 2 lipid coating (CaCO 3 @CuO 2 @L). This system aimed to comprehensively modulate the tumor microenvironment and trigger "cuproptosis" in hepatocellular carcinoma (HCC) through the interaction between copper ions and peroxides. Experimental results revealed that the CaCO 3 @CuO 2 @L exhibited a distinct watermelon shape, with CuO 2 evenly distributed within the CaCO 3 nanoparticles. The nanoparticles had an average size of approximately 191 nm. In vitro studies demonstrated that the nanoparticles released CuO 2 in a slightly acidic environment while simultaneously elevating pH levels, reducing glutathione (GSH), and increasing oxygen production. Within liver cancer cells, the CaCO 3 @CuO 2 @L effectively regulated the acidity, GSH levels, and oxygen-depleted microenvironment through the "trinity" mechanism, ultimately inducing "cuproptosis" in HCC. Furthermore, in mouse models with transplanted tumors and orthotopic liver cancer tumors, the CaCO 3 @CuO 2 @L significantly suppressed tumor growth. By triggering "cuproptosis" in HCC, this study offers valuable insights for developing a comprehensive treatment approach for HCC. Ultimately, this research may pave the way for the clinical implementation of the drug delivery system based on "cuproptosis" in liver cancer treatment.

Topping, an important tree shaping and pruning technique, can promote the outgrowth of citrus axillary buds. However, the underlying molecular mechanism is still unclear. In this study, spring shoots of Citrus reticulata 'Huagan No.2' were topped and transcriptome was compared between axillary buds of topped and untopped shoots at 6 and 11 days after topping (DAT). 1944 and 2394 differentially expressed genes (DEGs) were found at 6 and 11 DAT, respectively. KEGG analysis revealed that many DEGs were related to starch and sucrose metabolism, signal transduction of auxin, cytokinin and abscisic acid. Specially, transcript levels of auxin synthesis, transport, and signaling-related genes (SAURs and ARF5), cytokinin signal transduction related genes (CRE1, AHP and Type-A ARRs), ABA signal responsive genes (PYL and ABF) were up-regulated by topping; while transcript levels of auxin receptor TIR1, auxin responsive genes AUX/IAAs, ABA signal transduction related gene PP2Cs and synthesis related genes NCED3 were down-regulated. On the other hand, the contents of sucrose and fructose in axillary buds of topped shoots were significantly higher than those in untopped shoots; transcript levels of 16 genes related to sucrose synthase, hexokinase, sucrose phosphate synthase, endoglucanase and glucosidase, were up-regulated in axillary buds after topping. In addition, transcript levels of genes related to trehalose 6-phosphate metabolism and glycolysis/tricarboxylic acid (TCA) cycle, as well to some transcription factors including Pkinase, Pkinase&#95;Tyr, Kinesin, AP2/ERF, P450, MYB, NAC and Cyclin&#95;c, significantly responded to topping. Taken together, the present results suggested that topping promoted citrus axillary bud outgrowth through comprehensively regulating plant hormone and carbohydrate metabolism, as well as signal transduction. These results deepened our understanding of citrus axillary bud outgrowth by topping and laid a foundation for further research on the molecular mechanisms of citrus axillary bud outgrowth., 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.)

Nucleation is a fundamental process that determines the structure, morphology, and properties of crystalline materials, and is difficult to control because it is unpredictable. Here, we demonstrate a new method to control the protein crystal nucleation using a magnetic force, where we manipulate the movement and coalescence of nucleation precursors by adding paramagnetic salt into the crystallization solution to constrain the number and position of nucleation. We found that protein nucleation could be significantly affected by the magnetic force that the gradient magnetic fields generate. When the magnetization force is sufficiently enough, nucleation can be confined to the crystallization solution with no interface contact; therefore, only one crystal nucleus appears, which results in noncontact suspension growth of a single crystal in the crystallization solution system. Under these situations, the nucleation rate significantly decreases due to the coalescence of the dense liquid phase, and the crystal growth rate also decreases due to the suppression of convection, which increases the crystal quality. Our findings provide a new method for the noncontact control of crystal nucleation and demonstrate that externally applied physical environments can be used to affect the liquid-liquid phase separation process., 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.)

Diffusion magnetic resonance imaging (dMRI) is a non-invasive method for capturing the microanatomical information of tissues by measuring the diffusion weighted signals along multiple directions, which is widely used in the quantification of microstructures. Obtaining microscopic parameters requires dense sampling in the q space, leading to significant time consumption. The most popular approach to accelerating dMRI acquisition is to undersample the q-space data, along with applying deep learning methods to reconstruct quantitative diffusion parameters. However, the reliance on a predetermined q-space sampling strategy often constrains traditional deep learning-based reconstructions. The present study proposed a novel deep learning model, named attention-based q-space deep learning (aqDL), to implement the reconstruction with variable q-space sampling strategies. The aqDL maps dMRI data from different scanning strategies onto a common feature space by using a series of Transformer encoders. The latent features are employed to reconstruct dMRI parameters via a multilayer perceptron. The performance of the aqDL model was assessed utilizing the Human Connectome Project datasets at varying undersampling numbers. To validate its generalizability, the model was further tested on two additional independent datasets. Our results showed that aqDL consistently achieves the highest reconstruction accuracy at various undersampling numbers, regardless of whether variable or predetermined q-space scanning strategies are employed. These findings suggest that aqDL has the potential to be used on general clinical dMRI datasets.

Albuminuria is a hallmark of diabetic nephropathy (DN). Podocyte injury significantly contributes to proteinuria in DN. Our study found that lncRNA EVF-2 is upregulated in podocytes of DN patients, correlating with cell cycle re-entry and inflammation. Specific knockout or knockdown of lncRNA evf-2 in diabetic mice or cultured podocytes alleviated podocyte injury associated with these processes. RNA sequencing of evf-2-overexpressing podocytes unveiled a predominant enrichment of upregulated mRNAs in cell cycle and inflammation pathways, with alternative splicing in cell cycle-related mRNAs Ccnb1 and Tacc3. Chromatin isolation by RNA purification-mass spectrometry (ChIRP-MS) analysis highlighted the involvement of ribonucleoprotein complex and mRNA processing-related proteins, with hnRNPU as the main binding partner of evf-2 in spliceosomes. Knockdown of hnRNPU partially restored the upregulation of mRNAs induced by evf-2 overexpression, altering splice variants of Ccnb1 and Tacc3. This study is the first to reveal the splice variants of cell cycle-related genes in DN and elucidate the interaction between lncRNA evf-2 and hnRNPU. This interaction culminates in the upregulation of cell cycle-related genes and inflammatory factors through diverse pathways, potentially involving transcriptional activation, RNA stability modulation, alternative splicing or translational regulation. This highlights potential novel pathways for DN treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Photodynamic therapy (PDT) has emerged as a preferred nonsurgical treatment in clinical applications due to its capacity to selectively eradicate diseased tissues while minimizing damage to normal tissue. Nevertheless, its clinical efficacy is constrained by the limited penetration of visible light. Although near-infrared (NIR) lasers offer enhanced tissue penetration, the dearth of suitable photosensitizers and a pronounced imaging-treatment disparity pose challenges. Additionally, clinical implementation via optical fiber implantation carries infection risks and necessitates minimally invasive surgery, contradicting PDT's noninvasive advantage. In this study, we introduce a brilliant approach utilizing aggregation-induced emission luminogens (AIEgen) to develop a visible-light penetrator (VLP), coupled with wireless light emitting diodes (LEDs), enabling deep photodynamic therapy. We validate the therapeutic efficacy of this visible-light penetrator in tissues inaccessible to conventional PDT, demonstrating significant suppression of inflammatory diffusion in vivo using AIEgen TBPPM loaded within the VLP, which exhibits a transmittance of 86% in tissues with a thickness of 3 mm. This innovative visible-light penetrator effectively overcomes the substantial limitations of PDT in clinical settings and holds promise for advancing phototherapy.

With the gradually increasing requirement for freshwater, capacitive deionization (CDI) as a burgeoning desalination technique has gained wide attention owing to its merits of easy operation, high desalination efficiency, and environmental friendliness. To enhance the desalination performance of CDI, different CDI architectures are designed, such as membrane CDI, hybrid CDI, and flow-electrode CDI. However, these CDI systems have their own drawbacks, such as the high cost of membranes, capacity limitation of carbon materials and slurry blockage, which severely limit their practical application. Notably, rocking-chair CDI (RCDI) composed of symmetric electrode materials delivers excellent desalination performance because of its special dual chamber structure, which can not only break through the capacity limitations of carbon materials, but also deliver a continuous desalination process. Although RCDI showcases high promise for efficient desalination, few works systematically summarize the advantages and applications of RCDI in the desalination field. This review offers a thorough analysis of RCDI, focusing on its electrode materials, structure designs and desalination applications. Furthermore, the desalination performances of RCDI and other CDI architectures are compared to demonstrate the advantages of RCDI and the prospect of RCDI is elucidated.

Swift heavy ion (SHI) irradiation is an effective method for modulating the properties of thin oxide films by introducing defects, strains, and structural transformations. Here, we applied 516 MeV Xe 31+ irradiation to BaTiO 3 (BTO) thin films grown on Nb:SrTiO 3 substrates to induce the generation of tracks and nanohillocks. Memristors with BTO films irradiated at a fluence of 5 × 10 10 ions cm -2 displayed excellent retention and endurance characteristics. Moreover, the memristors exhibited highly stable synaptic plasticity functions such as excitatory/inhibitory post-synaptic currents (E/IPSC) and paired-pulse facilitation/depression (PPF/D). The memristors achieved a discrimination accuracy of 92.5% on given handwritten digit data by an artificial neural network with supervised learning. These results verify that the judicious application of SHI irradiation on thin oxide films is a viable strategy for exploring neuromorphic computation.

One new compound named sinulariapeptide F (1) together with one known butyrolactone (2) and seven known peptides (3-9) were isolated from the fungus Simplicillium sp. SCSIO 41222. Their structures and absolute configurations were established using HRESIMS, NMR spectroscopy ( 1 H, 13 C, HSQC, HMBC) and marfey's method. All of these compounds were assessed their inhibitory activity of acetylcholinesterase (AChE) and pancreatic lipase (PL). Compounds 4 and 6 were selected to test for the inhibitory activity against programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1). The results indicated that compound 4 displayed potent inhibition activity against PD-1/ PD-L1 with an IC 50 value of 0.656 μM. Furthermore, the docking analysis demonstrated the interactions between 4 and proteins, suggesting PD-L1 to be a probable target for compound 4., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

In this paper, active polysaccharides were extracted from Brassica rapa L. polysaccharide (BRP), and structural characterization was preliminarily investigated. Its immunomodulatory activity and molecular biological mechanisms in cyclophosphamide-induced immunosuppressed mice were also explored, as well as its effects on intestinal microbiota. Results indicate that BRP is an acidic heteropolysaccharide with the main components of Ara, GalA, and GlcA and has α- and β-glycosidic linkages with pyranose bonds. The results of the study showed that BRP could effectively improve the thymus and spleen indices and repair Cy-induced immune tissue damage in immunosuppressed mice. Meanwhile, BRP increased the immune cell activity and antioxidant levels in mice. In addition, BRP increased the secretion of cytokines (IL-1β, IL-6, IL-10, and TNF-α) and immunoglobulins (IgA, IgG) in mouse serum. It also regulates the relative expression of genes related to the TLR4/NF-κB signaling pathways as well as regulates the diversity and composition of mouse intestinal microbiota. In conclusion, BRP was able to regulated the immune function in immunosuppressed mice, providing a theoretical basis for the development of immunomodulators., (© 2024 Institute of Food Technologists.)

The characteristics of ion-scale turbulence in the presence of a magnetic island are numerically investigated using a gyrokinetic model in fusion plasma. We observe that in the absence of the usual ion temperature gradient (ITG) drive gradient, a magnetic island and its flatten effect could drive ITG instability. The magnetic island (MI) not only drives high-n modes of ITG instability but also induces low-n modes of vortex flow. Moreover, as the magnetic island width increases, the width of the vortex flow also increases. This implies that wider islands may more easily induce vortex flows. The study further indicates that the saturated amplitude and transport level of MI-induced ITG turbulence vary with different magnetic island widths. In general, larger magnetic islands enhance both particle and heat transport. When the magnetic island width reaches to 21ρ i , the turbulence-driven transport becomes the same level with the cases that ITG is driven by pressure gradients. Our findings indicate the presence of intricate nonlinear effects in the modulation of plasma turbulence by MIs. These effects are of significant importance for comprehending the phenomenon of nonlinear coupling in forthcoming tokamaks such as ITER., (© 2024. The Author(s).)

Purpose: Laryngoscopy is routinely used for suspicious vocal cord lesions with limited performance. Accumulated studies have demonstrated the bright prospect of deep learning in processing medical imaging. In this study, we perform a systematic review and meta-analysis to investigate diagnostic utility of deep learning in laryngoscopy., Methods: The study was performed according to the Primary Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We comprehensively retrieved articles from the PubMed, Scopus, Embase, and Web of Science up to July 14, 2024. Eligible studies with application of deep learning algorithm in laryngoscopy were assessed and enrolled by two independent investigators. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio with 95% confidence intervals (CIs) were calculated using a random effects model., Results: We retained 9 eligible studies adding up to 106,175 endoscopic images for the meta-analysis. The pooled sensitivity and specificity to diagnose laryngeal cancer were 0.95(95% CI: 0.85-0.98) and 0.96 (95% CI: 0.91-0.98). The area under the curve of deep learning was 0.99 (95%CI: 0.97-0.99)., Conclusion: Deep learning demonstrated excellent diagnostic efficacy in assessing laryngeal cancer with laryngoscope images in current studies, which manifests its potential of aiding endoscopist for laryngeal cancer diagnosis and clinical decision making., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lipid droplets (LDs) as spherical dynamic subcellular organelles, play an important role in various cellular functions such as protein degradation, lipid metabolism, energy storage, signal transduction, and membrane formation. Abnormal function of LDs will lead to a series of diseases and hence monitoring the status of LDs is particularly important. In this study, we synthesized a water-insoluble red fluorescent emitting small molecule fluorescent probe (TPE-TCF), which exhibited aggregation-induced emission (AIE) properties and enabled highly selective real-time imaging of LDs (Pearson's R value was 0.90). More interestingly, this probe was able to track the dynamic processes of LDs in living cells, including lipophagy, and monitor fatty liver disease in mice. Therefore, TPE-TCF with red fluorescence emission, good biocompatibility, large Stokes shift, AIE properties, LDs imaging, and fatty liver recognition capabilities can be practically used in more LDs-related diseases., 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.)

Solar-driven carbon dioxide (CO 2 ) reduction into C 2+ products such as ethylene represents an enticing route toward achieving carbon neutrality. However, due to sluggish electron transfer and intricate C-C coupling, it remains challenging to achieve highly efficient and selective ethylene production from CO 2 and H 2 O beyond capitalizing on Cu-based catalysts. Herein, we report a judicious design to attain asymmetric C-C coupling through interfacial defect-rendered tandem catalytic centers within a sulfur-vacancy-rich MoS x /Fe 2 O 3 photocatalyst sheet, enabling a robust CO 2 photoreduction to ethylene without the need for copper, noble metals, and sacrificial agents. Specifically, interfacial S vacancies induce adjacent under-coordinated S atoms to form Fe-S bonds as a rapid electron-transfer pathway for yielding a Z-scheme band alignment. Moreover, these S vacancies further modulate the strong coupling interaction to generate a nitrogenase-analogous Mo-Fe heteronuclear unit and induce the upward shift of the d-band center. This bioinspired interface structure effectively suppresses electrostatic repulsion between neighboring *CO and *COH intermediates via d-p hybridization, ultimately facilitating an asymmetric C-C coupling to achieve a remarkable solar-to-chemical efficiency of 0.565% with a superior selectivity of 84.9% for ethylene production. Further strengthened by MoS x /WO 3 , our design unveils a promising platform for optimizing interfacial electron transfer and offers a new option for C 2+ synthesis from CO 2 and H 2 O using copper-free and noble metal-free catalysts.

Background: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment., Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels., Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14-1.33; P<0.001), and poor outcome (OR=1.34; 95% CI, 1.26-1.45; P<0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42-1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49-2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification., Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies., Competing Interests: All the authors declare that they have no conflict of interest relevant to the manuscript., (© 2024 Guo et al.)

Background: Two-line hybrid wheat technology system is one way to harness wheat heterosis both domestically and internationally. Seed vigor is a crucial parameter for assessing seed quality, as enhanced seed vigor can lead to yield increments of over 20% to a certain extent. MicroRNAs (miRNAs) were known to participate in the development and vigor of seed in plants, but its impact on seed vigor in two-line hybrid wheat remains poorly elucidated., Results: The hybrid (BS1453/11GF5135) wheat exhibited superiority in seed vigor and anti-aging capacity, compared to its male parent (11GF5135, MP) and female parent (BS1453, FP). We identified four miRNAs associated with seed vigor, all of which are novel miRNAs. The majority of targets of miRNAs were related to ubiquitin ligases, kinases, sucrose synthases and hydrolases, involving in starch and sucrose metabolism, hydrolysis, catalysis, plant hormone signal transduction, and other pathways, which played crucial roles in seed development. Additionally, we also found miR531 was differentially expressed in both male parent and hybrid, and its target gene was a component of the E1 subunit of α-ketoate dehydrogenase complex, which interacted with dihydrolipoamide acetyltransferase (E2) and dihydrolipoyl dehydrogenase (E3). Finally, We established a presumptive interaction model to speculate the relationship of miR531 and seed vigor., Conclusions: This study analyzed the seed vigor of two-line hybrid wheat, and screened seed vigor-related miRNAs. Meanwhile speculated the genetic relationship of hybrid and parents, in terms of miRNAs. Consequently, the present study provides new insights into the miRNA-mediated gene and protein interaction network that regulates seed vigor. These findings hold significance for enhancing the yield and quality of two-line hybrid wheat, facilitating its future applications., (© 2024. The Author(s).)

The significance of health literacy for elderly individuals with chronic illnesses lies in managing and delaying disease development, which is affected by personal and environmental factors. Family communication can provide an emotional support environment; self-efficacy is an important factor of subjective initiative and personality. A relatively persistent thinking and behavior pattern can affect the environment, subjective initiative, and individual health outcomes. This study aims to explore the effects of the Big Five personality traits on the health literacy of elderly individuals with chronic illnesses and to hypothesize that family communication and self-efficacy mediate the Big Five personalities and health literacy. A cross-sectional study of 2251 elderly individuals with chronic diseases was conducted through nationwide random quota sampling. The structural equation model was used to explore the mediating role of family communication and self-efficacy between the Big Five personality and health literacy. Family communication played a simple mediating role in the influence of extraversion, agreeableness, conscientiousness, and neuroticism on health literacy. Self-efficacy played a simple mediating role in the influence of the Big Five personalities on health literacy. Self-efficacy and family communication played a chain mediating role between extraversion, agreeableness, conscientiousness, neuroticism, and health literacy. Nurses can enhance the health literacy of elderly individuals with chronic illnesses with extraversion, agreeableness, conscientiousness, and neuroticism through family communication and self-efficacy while promoting the health literacy of those with openness through self-efficacy., (© 2024. The Author(s).)

The impact of a concentrate-rich (CR) diet on the gut microbiome and epithelium homeostasis is well documented. However, it has not been systematically studied whether and how host-microbial interaction contributes to the immune homeostasis in the rumen and colon of lambs fed alfalfa hay and wheat straw, alone or combined, in a CR diet. In all, 63 lambs (initial body weight, 16.69 ± 1.50 kg) were randomly allotted to three dietary groups, each consisting of three pens with seven lambs per pen. Over 14 weeks, the lambs were fed diets as follows: 60% concentrate supplemented with either 40% wheat straw (WG), 20% alfalfa hay combined with 20% wheat straw (MG), or 40% alfalfa hay (AG). The present findings showed that lambs in the AG group had greater ( P < 0.05) IgG and lower ( P = 0.067) tumor necrosis factor-alpha concentrations relative to those in the MG and WG groups. The 16S rRNA analysis highlighted that various bacterial phyla and genera in the rumen and colon preferentially degrade fiber and starch derived from alfalfa hay and wheat straw. The weighted gene co-expression network analysis revealed that the bacterial genera from the Firmicutes are broadly associated with genes involved in various signaling pathways, underscoring the potential role of Firmicutes as key drivers of host-microbial interactions under the present feeding conditions. These findings shed light on the fact that the rumen and colon immune homeostasis is distinctively influenced by diets of alfalfa hay, wheat straw, or their combination in a CR diet. Further studies should examine the prolonged effects of replacing wheat straw with alfalfa hay in a concentrate-rich diet formulated to provide equivalent neutral detergent fiber levels. This could reveal how various forage fibers influence host-microbial interactions and gut health.IMPORTANCEIn contemporary feedlots, a growing trend is to feed animals a concentrate-rich (CR) diet that could disrupt the synchronized interplay between microbes and host metabolism, leading to altered metabolic functions. Wheat straw and alfalfa hay have different levels of protein and neutral detergent fiber, each with varying rates of digestion. It is unclear how including alfalfa hay and wheat straw, alone or combined in a CR diet, influences the host-microbial consortia and immune homeostasis. Herein, we showed that rumen and colon showed differential immune responses to the alfalfa hay, wheat straw, or both. Bacterial genera preferentially degrade fiber and starch derived from alfalfa hay, wheat straw, or both. Bacterial genera from Firmicutes phylum play a pivotal role in driving the host-microbial interactions, as indicated by their extensive association with genes across various signaling pathways., Competing Interests: The authors declare no conflict of interest.

NSUN5, a key member of the M5C methylation family, plays a significant role in fundamental biological processes like cell proliferation and differentiation. However, its specific function and mechanisms in gastric cancer remain insufficiently understood. Initially, we examined NSUN5's differential expression in gastric cancer versus normal tissues, along with survival trends, associated signaling pathways, and immune infiltration using the TCGA database. Subsequently, we conducted immunohistochemistry experiments to assess NSUN5 expression in gastric cancer tissues. Gain-and loss-of-function experiments were carried out to investigate NSUN5's impact on the proliferation, stemness, and migratory capabilities of gastric cancer cells, as well as the expression of vital proteins in pertinent signaling pathways. Our findings demonstrate that NSUN5 is not only overexpressed in gastric cancer tissues, but also positively associated with tumor stage and inversely linked with patient prognosis. NSUN5 promotes the in vitro proliferation, stemness, and migration of gastric cancer cells, and the in vivo growth of these cells, chiefly through the activation of the WNT/β-catenin signaling pathway. Additionally, NSUN5 appears to diminish the infiltration of CD8+ T cells in gastric cancer, contributing to immune evasion. In conclusion, NSUN5 functions as a proto-oncogene in the progression of gastric cancer and may serve as a potential therapeutic target., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Cadmium (Cd) has been classified as a Class I carcinogen, but the mechanism of its carcinogenicity is still unknown. Our previous study demonstrated that 2 μM CdCl 2 induced autophagy in A549 cells. In this study, we investigated the role of ATF4/PHGDH in Cd-induced autophagy and increased glycolysis. First, BALB/c mice were subcutaneously injected with A549 cells co-treated with or without Cd and siPHGDH to establish a xenograft tumor model, which demonstrated that PHGDH promotes Cd-induced autophagy in vivo. Cd-exposed A549 cells were treated with siPHGDH and 0.4 mM glycine (Gly), respectively. Western blot analysis and Acridine orange staining revealed that PHGDH promotes Cd-induced autophagy. Using 4-PBA (5 mM), the inhibitor of ER stress, or Tm (0.1 μg/ml), the inducer of ER stress, inhibited Cd-induced PHGDH expression. After co-treatment with siPHGDH, PHGDH was determined to mediate ER stress-induced autophagy. Furthermore, transfection with siATF4 inhibited Tm-induced PHGDH expression. ChIP-qPCR experiments demonstrated the transcription regulatory mechanism of ATF4 on PHGDH. Meanwhile, the role of ER stress/PHGDH/autophagy in Cd-promoted cell migration was explored by scratch assay. Finally, the role of ER stress/PHGDH/autophagy in Cd-induced glycolysis was unveiled. In summary, the transcriptional regulation of PHGDH by ATF4 plays a crucial role in Cd-induced autophagy triggered by ER stress. The axis of ER stress/PHGDH/autophagy is important in Cd-induced cell migration by enhancing glycolysis., 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: Central serous chorioretinopathy (CSC) is a disqualifying condition for pilots because of the importance of good vision to their jobs. The objective of this study was to evaluate the clinical diagnosis, treatment, and aviation medical assessment principles for CSC in military pilots., Methods: The clinical data and aviation medical assessments of 15 pilots with CSC who were admitted to the Air Force Medical Center between January 2003 and December 2021 were analyzed, and three typical cases are reported. The relevant literature evaluation was conducted on 32 non-pilot patients with CSC., Results: The mean age of the 15 pilots was 37.47 ± 4.21 years, and they were all male. Fourteen were affected in a single eye (4 in the right eye and 10 in the left eye), while one was affected in both eyes. Two pilots were nonsmokers and did not consume alcohol; one was a smoker; four pilots consumed alcohol on a regular basis; and eight pilots were smokers and consumed alcohol on a regular basis. The mean best-corrected visual acuity (BCVA) increased from 0.83 ± 0.33 at the initial visit to 0.95 ± 0.44 at the final visit. The non-pilot group included 32 patients, 29 of whom were male and 3 of whom were female, with a mean age of 37.16 ± 10.02 years. Thirty-one patients had single-eye involvement (17 of the right eye and 14 of the left eye), while one patient had involvement of both eyes. Seventeen patients were nonsmokers and did not consume alcohol; two were smokers; four consumed alcohol on a regular basis; and nine were smokers and consumed alcohol on a regular basis. The mean BCVA increased from 0.64 ± 0.28 at the first visit to 0.90 ± 0.30 at the final visit. Patients in the pilot group had a high recurrence rate, which was associated with a low final BCVA and led to their disqualification from flying., Conclusion: Pilot and non-pilot patients did not differ significantly in terms of CSC clinical data. Chronic and recurrent CSC can be a vision-threatening disease; therefore, pilots must receive accurate and timely diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Developing superior cancer cell recognition probes is crucial for the development of tumor therapy and cancer early screening materials. In this study, we first achieved effective recognition of MCF-7 breast cancer cells using natural collagen probes. Through cell adhesion, cancer cell selective capture, and flow cytometry techniques, the binding efficiency of mammalian-derived collagens (bovine Achilles tendon collagen, porcine skin collagen) and fish-derived collagens (turbot skin collagen, grass carp skin collagen, mandarin fish skin collagen) to cancer cells (MCF-7 breast cancer cells) and normal cells (human umbilical vein endothelial cells, HUVECs) was analyzed and compared. The feasibility of different source collagens as probes for recognition of MCF-7 cells was explored in vitro. The results indicated that mammalian-derived collagens had a superior advantage over fish-derived collagens in recognizing MCF-7 cells, with bovine Achilles tendon collagen achieving a capture rate of up to 64.7 % in a multicellular co-culture system. Furthermore, in vivo imaging of BALB/c tumor-bearing mice confirmed the high-efficiency targeted recognition performance of the bovine Achilles tendon collagen probe for MCF-7 cells., Competing Interests: Declaration of competing interest 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 B.V.)

Intervertebral disc degeneration (IVDD) is a prevalent orthopedic condition with lower back pain as the predominant clinical presentation that challenges clinical treatment with few therapeutic options. Duhuo Jisheng Decoction (DHJSD) has been proven effective in the therapy of IVDD, but the precise underlying mechanisms remain not fully elucidated. The current study was designed to test our hypothesis that DHJSD may systematically correct the phenotypic disruption of the gut microbiota and changes in the serum metabolome linked to IVDD. Analysis of the active ingredients of DHJSD by ultra high performance liquid chromatography. An integrated metagenomic and metabonomic approach was used to analyze feces and blood samples from normal and IVDD rats. Compared to the control group, fiber ring pinning on the caudal 3 to caudal 5 segments of the rats caused IVDD and significantly altered the compositions of the intestinal microbiota and serum metabolites. Integrated analysis revealed commonly-altered metabolic pathways shared by both intestinal microbiota and serum metabolome of the IVDD rats. DHJSD inhibited the degenerative process and restored the compositions of the perturbed gut microbiota, particularly the relative abundance of commensal microbes of the Prevotellaceae family. DHJSD also corrected the altered metabolic pathways involved in the metabolism of glycine, serine, threonine, valine, the citric acid cycle, and biosynthesis of leucine and isoleucine. DHJSD inhibited the disc degeneration process by an integrated metagenomic and metabonomic mechanism to restore the microbiome profile and normalize the metabonomic pathways., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song 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.)

Purpose: Collaboration provides valuable data for robust artificial intelligence (AI) model development. Federated learning (FL) is a privacy enhancing technology that allows collaboration while respecting privacy via the development of models without raw data transfer. However state-of-the-art FL models still face challenges in non-independent and identically distributed (non-i.i.d.) health care settings and remain susceptible to privacy breaches. We propose a novel FL framework coupled with blockchain technology to address these challenges., Design: Retrospective multicohort study SUBJECTS AND METHODS: 27,145 images from Singapore, China and Taiwan were used to design a novel FL aggregation method for the detection of myopic macular degeneration (MMD) from fundus photographs and macular disease from optical coherence tomography (OCT) scans in feature distribution skew and label distribution imbalance scenarios. We further performed adversarial attacks (label flipping and clean label). As proof of concept, blockchain was incorporated into FL to demonstrate secure transfer of model updates across collaborating sites., Main Outcome Measures: We evaluated our FL model performance in MMD and OCT classification and compared our model against state-of the-art FL and centralized models., Results: Our FL model showed robust performance with areas under the receiving operating characteristic curves (AUC) of 0.868±0.009 for MMD detection and 0.970±0.012 for OCT macular disease classification. In label flipping attack, our FL model had an AUC of 0.861±0.019, similar to the centralized model (AUC 0.856± 0.015) and higher than other FL models (AUC 0.578-0.819) In clean label attack, our FL model had an AUC of 0.878±0.006 which was comparable to the centralized model (AUC 0.878±0.001) and superior to other state-of-the-art FL models with AUC of 0.529-0.838. Simulation showed that the additional time with blockchain in one global epoch was around 5 seconds. The addition of blockchain to the FL framework was feasible with a minimal impact on model development time., Conclusions: Our proposed FL algorithm overcomes the shortcoming of the traditional FL in non i.i.d. situations and remains robust to against adversarial attacks. The integration of blockchain adds further security during the transfer of model updates. Blockchain-enabled FL can be a trusted platform for collaborative health AI research., (Copyright © 2024. Published by Elsevier Inc.)

The duck embryo fibroblast cell line CCL-141, which is currently the only commercialized duck cell line, has been underexplored in adipogenesis research. (1) Background: This study establishes an experimental protocol to induce adipogenesis in CCL-141 cells, addressing the importance of understanding gene functions in this process. (2) Methods: Chicken serum, fatty acids, insulin, and all-trans retinoic acid were used to treat CCL-141 cells, with adipogenesis confirmed by Oil Red O staining and gene expression quantification. CRISPR/Cas9 technology was applied to knockout PPARγ , and the resulting adipogenic phenotype was assessed. (3) Results: The treatments promoted adipogenesis, and the knockout of PPARγ validated the cell line's utility for gene function studies. (4) Conclusions: CCL-141 cells are a suitable model for investigating duck adipogenesis, contributing to the understanding of regulatory factors in this biological process.

Macroscale functional gradient techniques provide a continuous coordinate system that extends from unimodal regions to transmodal higher-order networks. However, the alterations of these functional gradients in AD and their correlations with cognitive terms and gene expression profiles remain to be established. In the present study, we directly studied the functional gradients with functional MRI data from seven scanners. We adopted data-driven meta-analytic techniques to unveil AD-associated changes in the functional gradients. The principal primary-to-transmodal gradient was suppressed in AD. Compared to NCs, AD patients exhibited global connectome gradient alterations, including reduced gradient range and gradient variation, increased gradient scores in the somatomotor, ventral attention, and frontoparietal regions, and decreased in the default mode network. More importantly, the Gene Ontology terms of biological processes were significantly enriched in the potassium ion transport and protein-containing complex remodeling. Our compelling evidence provides a new perspective in understanding the connectome alterations in AD., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: The highly heterogeneity of neuropsychiatric symptoms (NPSs) hinder further exploration of their role in neurobiological mechanisms and Alzheimer's disease (AD). We aimed to delineate NPS patterns based on brain macroscale connectomics to understand the biological mechanisms of NPSs on the AD continuum., Methods: We constructed Regional Radiomics Similarity Networks (R2SN) for 550 participants (AD with NPSs [AD-NPS, n=376], AD without NPSs [AD-nNPS, n=111], and normal controls [n=63]) from CIBL study. We identified R2SN connections associated with NPSs, and then cluster distinct subtypes of AD-NPS. An independent dataset (n=189) and internal validation were performed to assess the robustness of the NPS subtypes. Subsequent multiomics analysis were performed to assess the distinct clinical phenotype and biological mechanisms in each NPS subtype., Results: AD-NPS patients were clustered into severe (n=187), moderate (n=87), and mild NPS (n=102) subtypes, each exhibiting distinct brain network dysfunction patterns. A high level of consistency in clustering NPS was internally and externally validated. Severe and moderate NPSs showed significant cognitive impairment, increased plasma p-Tau 181 levels, extensive decreased brain volume and cortical thickness, and accelerated cognitive decline. Gene set enrichment analysis (GSEA) revealed enrichment of differentially expressed genes in ion transport and synaptic transmission with variations for each NPS subtype. Genome-wide association studies (GWAS) analysis defined the specific gene loci for each subtype of AD-NPS (i.e, logical memory), aligning with clinical manifestations and progression patterns., Conclusions: This study identified and validated three distinct NPS subtypes, underscoring the role of NPSs in neurobiological mechanisms and progression of the AD continuum., (Copyright © 2024. Published by Elsevier Inc.)

Cisplatin is a cornerstone chemotherapy for nasopharyngeal carcinoma (NPC); however, certain patients are ineligible for cisplatin-based regimens. This phase 2 trial (NCT04405622) evaluated the efficacy and safety of gemcitabine and toripalimab in previously untreated patients with recurrent or metastatic NPC who were either ineligible for cisplatin or had experienced severe adverse events from prior cisplatin-based treatments. Patients received gemcitabine (1,000 mg/m 2 ) and toripalimab (240 mg) every three weeks for six cycles, followed by toripalimab monotherapy for up to two years. The primary endpoint was the incidence of grade ≥3 adverse events, while secondary endpoints included objective response rate (ORR) and overall survival (OS). Of 30 screened patients, 21 were enrolled. No treatment-related fatalities occurred, with the most frequent adverse events being headache and nausea. The ORR was 61.9%, coupled with a disease control rate of 100%. Overall, gemcitabine plus toripalimab demonstrated low toxicity and promising efficacy for this specific patient cohort., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)