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AIM: To present a technique of transcapsular scleral fixation of the standard capsular tension ring (CTR) through equatorial capsulotomy and in-the-bag intraocular lens (IOL) implantation in subluxated lenses. METHODS: This retrospective consecutive case series included patients with subluxated lenses by more than 180 degrees who underwent lens extraction, transcapsular scleral fixation of the standard CTR through equatorial capsulotomy, in-the-bag IOL implantation and with at least 6mo follow-up. Preoperative and postoperative best corrected visual acuity (BCVA), intraocular pressure (IOP), complications, and postoperative IOL tilt and decentration were recorded. RESULTS: Nine eyes of 7 patients with a mean follow-up of 11.0±3.7mo were included in this study. The BCVA was significantly improved from 0.64±0.22 logMAR preoperatively to 0.21±0.19 logMAR postoperatively (P

Surface decontamination agents must effectively capture particle contaminants that have been deposited on surfaces. This ability is particularly important in scenarios involving nuclear fallout particles. In this technical note, the particle-capturing ability of a hydrogel, specifically, the polyvinyl alcohol-borax complex, was investigated as a potential decontamination agent for treating radioactively contaminated surface. For the assessment, simulated nuclear fallout particles, prepared by melting consolidation at 1200 °C followed by mechanical milling, were fixed on a stainless-steel substrate. The results demonstrated that the hydrogel effectively removed the simulated fallout particles from the surface. Even after only 1 min of contact time, the surface was left thoroughly clean, demonstrating the effectiveness of the polyvinyl alcohol-borax complex as a surface decontamination agent.

Abstract Due to the aim of developing sustainable energy systems, promoting the large‐scale accommodation of distributed renewable energy sources (DRESs) and flexible loads in DC distribution networks (DCDNs) is significant. The uncertainty of DRESs and the insufficient use of flexible loads pose a considerable challenge to the economical and safe operation of DCDNs. To address the challenge, this paper puts forward a two‐stage optimal scheduling model for the DCDNs considering flexible load response. The proposed model realises joint economic optimisation and reactive power optimisation, which is solved by the hybrid NSGAII‐MOPSO algorithm and the CPLEX. The performance of the proposed model in the modified Institute of Electrical and Electronics Engineers 33‐node system with the DCDNs is validated under different scenarios. The hybrid NSGAII‐MOPSO performs better in obtaining the Pareto front than the NSGA‐II and MOPSO individually. Compared to the traditional scheduling model, the proposed model can realise the power coordination of the flexible loads and energy storage systems to reduce the negative impact of uncertainty of DRESs while decreasing operating costs and carbon emissions by 3.94% and 36.4%. In addition, the proposed model can alleviate the network losses and ensure the node voltage for the DCDNs. Hence, the efficiency of the proposed model has been confirmed.

Abstract Background Immune dysregulation has been identified as a contributing factor in the pathophysiology of schizophrenia. This study aimed to investigate variations in specific immune regulators and their correlation with psychopathology and cognitive functions in male patients with chronic schizophrenia. Methods Employing a cross-sectional design, this study included 72 male patients with chronic schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status were utilized to assess psychopathology and cognitive functions, respectively. Results Serum levels of interleukin (IL)-4, IL-10, IL-12p40, IL-13, and monocyte chemoattractant protein-1 (MCP-1) were measured. There were significantly increased levels of IL-4, IL-13, and MCP-1, alongside decreased levels of IL-10 in patients compared to controls (all P

Abstract Information industry is one of the major drivers of the world economy. Its rapid growth, however, leads to severe heat problem which strongly hinders further development. This calls for a non-charge-based technology. Magnon, capable of transmitting spin information without electron movement, holds tremendous potential in post-Moore era. Given the cornerstone role of the field effect transistor in modern electronics, creating its magnonic equivalent is highly desired but remains a challenge. Here, we demonstrate a nonvolatile three-terminal lateral magnon field effect transistor operating at room temperature. The device consists of a ferrimagnetic insulator (Y3Fe5O12) deposited on a ferroelectric material [Pb(Mg1/3Nb2/3)0.7Ti0.3O3 or Pb(Zr0.52Ti0.48)O3], with three Pt stripes patterned on Y3Fe5O12 as the injector, gate, and detector, respectively. The magnon transport in Y3Fe5O12 can be regulated by the gate voltage pulses in a nonvolatile manner with a high on/off ratio. Our findings provide a solid foundation for designing energy-efficient magnon-based devices.

Structure reflects a variety of practices teachers use with the intent to guide students' behavior and increase academic success. A research synthesis was conducted on the role of classroom structure in the academic engagement, disengagement, competence beliefs, and achievement of preschool through high school students. A meta-analysis of 191 samples from 165 correlational studies revealed statistically significant correlations with achievement (0.11), engagement (0.28), and competence beliefs (0.22), and a statistically non-significant relationship with disengagement (-0.08). A meta-analysis of 71 samples from 46 structure intervention studies revealed a positive statistically significant average effect (g) on achievement (0.33), engagement (0.46), and disengagement (-0.34), but a statistically non-significant effect for competence beliefs (0.26). Consistent with a dual process model of engagement, associations were stronger for engagement than disengagement. Results related to variation suggested some universality, particularly across grade levels, and underscored the importance of emphasizing anticipatory strategies, minimizing the controlling aspects of structure, and considering the broader context, including the country context, income background of students, or whether structure is paired with other psychological supports. Methodological features also explained variation, highlighting the importance of using methods that center teachers' and students' experiences and align with the nature of the focal outcome.

Pure red cell aplasia (PRCA) is a rare complication of erythropoietin (EPO) therapy, characterized by a severe deficiency in red blood cell production. There is no guideline on the treatment for PRCA because there have been too few cases to perform prospective cohort studies. The main treatments for PRCA include immediate cessation of EPO, restrictive transfusion, and immunosuppressive therapies. A 35-year-old male patient with type 1 diabetic nephropathy was diagnosed with PRCA. Enarodustat and roxadustat were administered successively after discontinuation of EPO, but anemia did not improve, and the patient was maintained with weekly blood transfusions. Subsequently, the EPO-mimetic peptide pegmolesatide was administered, and the patient’s hemoglobin started to increase after 1 week and increased from 50 g/L to 92 g/L over approximately 3 months. Based on these findings, we speculate that pegmolesatide can provide a safe, effective, and convenient therapeutic strategy for PRCA in Chinese patients with chronic kidney disease.

Introduction Spasticity is a common complication of stroke, which is related to poor motor recovery and limitations in the performance of activities. Both transcranial magnetic stimulation (TMS) and extracorporeal shockwave therapy (ESWT) are effective treatment methods for poststroke spasticity (PSS). However, there is no existing study exploring the safety and effectiveness of TMS combined with ESWT for PSS.Methods and analysis This study will be a prospective, single-centre, randomised, factorial, controlled clinical trial. In this trial, 136 patients with PSS will be randomly divided into 4 groups: experimental group 1 (TMS), experimental group 2 (ESWT), experimental group 3 (ESWT+TMS) and control group, 34 patients in each group; all patients received routine rehabilitation. Outcome measures will be assessed by 4 time points: baseline (T0), 2 weeks after initiation of treatment (T1), 4 weeks after initiation of treatment (T2) and follow-up (4 weeks after the end of treatment, T3). The primary outcome is the modified Ashworth scale at T2. The secondary outcomes include the modified Tardieu scale for the degree of spasticity, the Fugl-Meyer assessment scale and range of motion (ROM) for motor function, the stroke-specific quality of life scale (SS-QOL) and modified Barthel index for activities of life, cortical excitability measured by TMS–surface electromyography (EMG), cerebral cortex oxygen concentrations measured by functional near-infrared spectroscopy (fNIRS) and Hmax/Mmax ratio measured by EMG.Ethics and dissemination This study protocol was approved by the Ethics Committee of the Army Medical Center of PLA (Approval No. 2024-04) on 24 January 2024. The study will be disseminated through peer-reviewed publications and conference presentations.Trial registration number This study was registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/; unique identifier: ChiCTR2400080862; data: 9 February 2024; study protocol V. 2.0).

Background Several previous cross‐sectional studies suggested that body roundness index (BRI) may be associated with cardiovascular disease (CVD). However, the association should be further validated. Our study aimed to assess the association of the BRI trajectories with CVD among middle‐aged and older Chinese people in a longitudinal cohort. Methods and Results A total of 9935 participants from the CHARLS (China Health and Retirement Longitudinal Study) with repeated BRI measurements from 2011 to 2016 were included. The BRI trajectories were identified by group‐based trajectory modeling. The primary outcome was incident CVD (stroke or cardiac events), which occurred in 2017 to 2020. Cox proportional hazards regression models were used to examine the association of BRI trajectories with CVD risk. Participants were divided into 3 BRI trajectories, named the low‐stable BRI trajectory, moderate‐stable BRI trajectory and high‐stable BRI trajectory, accounting for 49.81%, 42.35%, and 7.84% of the study population, respectively. Compared with participants in the low‐stable BRI trajectory group, those in the moderate‐stable and high‐stable BRI trajectory groups had an increased risk of CVD, with multivariable adjusted hazard ratios of 1.22 (95% CI, 1.09–1.37) and 1.55 (95% CI, 1.26–1.90), respectively. Furthermore, simultaneously adding the BRI trajectory to the conventional risk model improved CVD risk reclassification (all P

Abstract Background Polypharmacy is common in older adults with psychiatric disorders, but no consensus has reached about the reliable indicators evaluating the benefits and risks of drug-drug interactions (DDIs) in polypharmacy. We aimed to identify indicators suitable for evaluating the clinical significance of DDIs in polypharmacy in older adults with psychiatric disorders. Methods The online tools were used to distribute and collect the questionnaires. The Delphi method was applied to analyze experts’ opinions. The degree of authority and coordination of experts were analyzed using the coefficient of variation, coefficient of coordination, expert’s judgment factor, familiarity with the study content factor, and Kendall coordination coefficient. Statistical analysis was conducted using the IBM SPSS® Statistics Package version 26.0. Results After three rounds of expert consultation, five primary and eleven secondary indicators were identified. The primary “pharmacodynamic indicator” included “severity of adverse drug reactions”, “duration of adverse drug reaction”, “symptom relief”, “time to onset of symptomatic relief”, “number of days in hospital”, and “duration of medication”. The secondary “pharmacokinetic indicator” contained “dosage administered” and “dosing intervals”. The primary “patient tolerance indicator” contained one secondary indicator of “patient tolerability”. The primary indicator “patient adherence” contained one secondary indicator of “patient adherence to medication”. The primary indicator “cost of drug combination” contained one secondary indicator of “readmission”. These indicators were used to determine the clinical significance of DDIs during polypharmacy. Conclusions The clinical significance of drug combinations should be taken into account when polypharmacy is used in the elderly. The five primary indicators and eleven secondary indicators might be preferred to evaluate their risks and benefits. Medication management in this population requires a multidisciplinary team, in which nurses play a key role. Future research should focus on how to establish efficient multidisciplinary team workflows and use functional factors to assess DDIs in polypharmacy for psychiatric disorders.

Abstract Accumulating evidence suggests that imbalanced oxidative stress (OS) may contribute to the mechanism of schizophrenia. The aim of the present study was to evaluate the associations of OS parameters with psychopathological symptoms in male chronically medicated schizophrenia (CMS) and treatment-resistant schizophrenia (TRS) patients. Levels of hydrogen peroxide (H2O2), hydroxyl radical (·OH), peroxidase (POD), α-tocopherol (α-toc), total antioxidant capacity (TAC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assayed in males with CMS and TRS, and matched healthy controls. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The results demonstrated significant differences in the variables H2O2 (F = 5.068, p = 0.008), ·OH (F = 31.856, p

Abstract Yttrium iron garnet, a material possessing ultralow magnetic damping and extraordinarily long magnon diffusion length, is the most widely studied magnetic insulator in spintronics and magnonics. Field-free electrical control of perpendicular yttrium iron garnet magnetization with considerable efficiency is highly desired for excellent device performance. Here, we demonstrate such an accomplishment with a collinear spin current, whose spin polarization and propagation direction are both perpendicular to the interface. Remarkably, the field-free magnetization switching is achieved not only with a heavy-metal-free material, Permalloy, but also with a higher efficiency as compared with a typical heavy metal, Pt. Combined with the direct and inverse effect measurements, we ascribe the collinear spin current to the anomalous spin Hall effect in Permalloy. Our findings provide a new insight into spin current generation in Permalloy and open an avenue in spintronic devices.

In response to the long-standing environmental problems caused by mining, some green mining concepts and policies have been gradually developed. Nowadays, under the goal of carbon peaking and carbon neutrality, green mining is facing some new requirements such as low carbon production and ecological mining. It is necessary to explore the critical directions and key issues of green mining in the new era under the goal of energy saving and emission reduction, and to help the synergistic development of carbon neutrality and green mining. Taking green mining, carbon sources/sinks, emission reduction and sink enhancement as key focuses, through literature review and inductive analysis, the connotation and requirements of green mining under the “dual carbon” goal were summarized, and the research progress on carbon sources/sinks and emission reduction and sink enhancement under the background of green mining was analyzed, the research techniques related to carbon source and carbon sink accounting in mining areas were reviewed, and the strategies for the reduction of emission and increase of sink in green mining were explored. Green mining research has achieved abundant theoretical and practical results, and has a good foundation to face new development challenges. The existing management programs and assessment systems of green mining is complete, while the overall system is qualitative with basic recommended requirements. The method of accounting for the carbon footprint of mines based on the life cycle concept and the IPCC method is relatively mature, but some cautions are still needed in the process of life cycle division and accounting factor selection. Green mining should focus on energy and technology aspects to achieve the goal of emission reduction and sink enhancement. Under the background of “carbon peaking and carbon neutrality”, the attention of green mining related acceptance standards in energy saving and emission reduction needs to be enhanced, and the degree of quantification and enforceability of the index systems needs to be improved. The coal industry is crucial to both the carbon neutrality target and the green mining development, and needs to strengthen the carbon footprint accounting and emission reduction potential analysis of coal mines. In the study of mine emission reduction, more attention needs to be paid to the analysis of carbon source and carbon sink accounting generated by the reclamation and the scheme design for emission reduction in the whole life cycle of the mine.

With the widespread use of the Global Navigation Satellite System (GNSS), its signal vulnerabilities and security issues have become increasingly exposed. Enhanced Long-Range Navigation (eLoran), as a backup system for the GNSS, has gradually attracted widespread attention. This paper investigates and optimizes the eLoran/GNSS combined positioning algorithm. The main research contributions are as follows: (a) Correcting the incorrect application of spatial coordinate transformation relations in the existing literature and re-deriving the eLoran/GNSS combined positioning algorithm based on the Andoyer–Lambert formula. (b) Correcting the eLoran pseudorange positioning equation for altitude in the combined positioning algorithm, compensating for the lack of altitude parameters in eLoran to improve positioning accuracy. (c) Verifying the correctness of the algorithm through simulation analysis, exploring the impact of errors on the algorithm, and evaluating whether the correction of altitude contributes to improving positioning accuracy. (d) Verifying the simulation results through actual measurement analysis.

IntroductionThe successful outcome of a pregnancy depends on the proper functioning uterine epithelium. DNA damage binding protein 1 and cullin 4-associated factor 2 (DCAF2), a conserved substrate receptor for the cullin 4-RING E3 ubiquitin ligase (CRL4) complex, is essential for maintaining genome stability by facilitating ubiquitin-mediated degradation of substrates.MethodsTo better understand the physiological role of DCAF2 in female reproduction, we conducted a study using mice with conditional knockout (cKO) of DCAF2 in the uterus using the progesterone receptor Cre (PgrCre/+) mouse model.ResultsOur results showed the cKO mice were completely infertile, despite having ovarian function. The cKO mice exhibited severely thin uteri, demonstrating notable defects in both the uterine epithelium and a lack of glands. In addition, there were impaired proliferation and differentiation of epithelial cells in the cKO mice, ultimately resulting in failed implantation. Moreover, through deciphering the uterine transcriptome of cKO mice, we revealed crucial differentially expressed genes associated with steroid signaling. Further experiments have demonstrated cKO mice exhibit elevated uterine PGR signaling and reduced estrogen receptor signaling, although the levels of progesterone and estrogen remained unaltered. These alterations may contribute to defects in epithelium.DiscussionOverall, our findings highlight a previously unrecognized but indispensable role for DCAF2 in the development of uterine luminal and glandular epithelium by orchestrating PGR and estrogen receptor responses. Its deficiency in the uterus leads to mouse infertility.

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10−5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

Abstract Background Inflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology. Methods The study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function. Results Serum TNF-α and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F = 4.289, P = 0.016; F = 4.682, P = 0.011, respectively). Bonferroni correction demonstrated that serum TNF-α levels were significantly elevated in CMS patients (P = 0.022) and MMP-2 levels were significantly higher in TRS patients (P = 0.014) compared to healthy controls. In TRS patients, TNF-α was negatively correlated with age (r=-0.435, P = 0.015) and age of onset (r=-0.409, P = 0.022). In CMS patients, MMP-2 and TNF-α were negatively correlated with PANSS negative and total scores, and TNF-α was negatively correlated with PANSS general psychopathology scores (all P 0.05). Conclusion The results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.

Due to the convenience of speech synthesis, synthesized disguised speech poses a great threat to the security of speaker verification systems.In order to further enhance the ability of detecting the camouflage to the speaker verification system, a method of synthetic speech detection was put forward using the information in spectral domain of the synthetic speech spectrogram.The method employed the local phase quantization (LPQ) algorithm to describe frequency domain information in the speech spectrogram.Firstly, the spectrogram was divided into several sub-blocks, and then the LPQ was performed on each sub-block.After the histogram statistical analysis, the LPQ feature vector was obtained and used as the input feature of the random forest classifier to realize the synthetic speech detection.The experimental results demonstrate that the proposed method further reduces tandem detection cost function (t-DCF) and has better generalization ability.

Abstract Background Accumulating evidence has indicated that oxidative stress (OS) and matrix metalloproteinase-9 (MMP-9) may contribute to the mechanism of schizophrenia. In the present study, we aimed to evaluate the associations of OS parameters and MMP-9 levels with psychopathological symptoms in male chronic schizophrenia patients. Methods This study was an observational, cross-sectional, retrospective case-control study. Plasma hydrogen peroxide (H2O2), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), serum matrix metalloproteinase-9 (MMP-9), and tissue inhibitors of metalloproteinases-1 (TIMP-1) levels were assayed in 80 male patients with chronic schizophrenia and 80 matched healthy controls. Schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Multivariate regression was used to analyze relationships between OS parameters and MMP-9, and clinical symptoms. Results Our results demonstrated that levels of antioxidant enzymes, SOD, GSH-Px, H2O2, and MDA were significantly decreased, whereas CAT and MMP-9 levels were increased in patients with schizophrenia, when compared with healthy controls (all P 0.05). Conclusions Our results showed that alterations of plasma OS parameters in male patients with chronic schizophrenia were associated with psychopathology and MMP-9, suggesting that OS and neuroinflammation may play important role in the mechanism of schizophrenia.

Patterns of taxonomic and phylogenetic beta diversity and their relationships with environmental correlates can help reveal the origin and evolutionary history of regional biota. The Qinghai-Tibet Plateau (QTP) harbors an exceptionally diverse flora, however, a phylogenetic perspective has rarely been used to investigate its beta diversity and floristic regions. In this study, we used a phylogenetic approach to identify patterns of beta diversity and quantitatively delimit floristic regions on the Qinghai-Tibet Plateau. We also examined the relationships between multifaceted beta diversity, geographical distance, and climatic difference, and evaluated the relative importance of various factors (i.e., climate, topography and history) in shaping patterns of beta diversity. Sørensen dissimilarity indices indicated that patterns of species turnover among sites dominated the QTP. We also found that patterns of both taxonomic and phylogenetic beta diversity were significantly related to geographical distance and climatic difference. The environmental factors that contributed most to these patterns of beta diversity include annual precipitation, mean annual temperature, climatic gradients and climatic instability. Hierarchical dendrograms of dissimilarity and non-metric multidimensional scaling ordination based on phylogenetic beta diversity data identified ten floristic subregions in the QTP. Our results suggest that the contemporary environment and historical climate changes have filtered species composition among sites and eventually determined beta diversity patterns of plants in the QTP.

Using a batch thermophilic anaerobic system established with 60 mL serum bottles, the mechanism on how microbial enrichments obtained from magnetite-amended paddy soil via repeated batch cultivation affected methane production from acetate was investigated. Magnetite-amended enrichments (MAEs) can improve the methane production rate rather than the methane yield. Compared with magnetite-unamended enrichments, the methane production rate in MAE was improved by 50%, concomitant with the pronounced electrochemical response, high electron transfer capacity, and fast acetate degradation. The promoting effects might be ascribed to direct interspecies electron transfer facilitated by magnetite, where magnetite might function as electron conduits to link the acetate oxidizers (Anaerolineaceae and Peptococcaceae) with methanogens (Methanosarcinaceae). The findings demonstrated the potential application of MAE for boosting methanogenic performance during thermophilic anaerobic digestion. HIGHLIGHTS Magnetite boosted the syntrophic conversion of acetate to methane during thermophilic anaerobic digestion.; Magnetite-amended enrichments exhibited pronounced electrochemical response and electron transfer capacity.; Magnetite might act as electron conduits to link acetate oxidizers and methanogens.; Magnetite might facilitate the establishment of direct interspecies electron transfer.; The addition of magnetite altered the bacterial community composition.;

Paddy soils developed from various parent materials are widely distributed in the subtropical region in China and have a non-negligible but unclear potential to consume nitrous oxide (N2O) due to long-term flooding. This study selected three of the most common paddy soils in subtropical China, developing from quaternary red soil (R), lake sediment sand (S), and alluvial soil (C), to study their total N2O consumption and total nitrogen (N2) production using N2-free microcosm experiments. These paddy soils were treated with N2O addition (N2O treatment) or helium (He) addition (CK treatment) and incubated under flooding and anoxic conditions. The results showed that three alluvial soils (C1, C2, and C3) consumed over 99.93% of the N2O accumulated in the soil profile, significantly higher than R and S soils (p < 0.05). And the N2 production in three C soils was also significantly higher than other soils, accounting for 81.61% of the total N2O consumption. The main soil factors affecting N2O consumption in C, S, and R soils were soil clay content (p < 0.05), soil sand content (R2 = 0.95, p < 0.001), and soil available potassium (AK) (p < 0.01), respectively. These results indicate flooding paddy soils, no matter the parent materials developed, could consume extremely large amount of N2O produced in soil profiles.

IntroductionThe gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear.MethodsWe aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models.ResultsWe observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation.ConclusionIn summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

BackgroundTertiary lymphoid structures (TLS) is a particular component of tumor microenvironment (TME). However, its biological mechanisms in colorectal cancer (CRC) have not yet been understood. We desired to reveal the TLS gene signature in CRC and evaluate its role in prognosis and immunotherapy response.MethodsThe data was sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Based on TLS-related genes (TRGs), the TLS related subclusters were identified through unsupervised clustering. The TME between subclusters were evaluated by CIBERSORT and xCell. Subsequently, developing a risk model and conducting external validation. Integrating risk score and clinical characteristics to create a comprehensive nomogram. Further analyses were conducted to screen TLS-related hub genes and explore the relationship between hub genes, TME, and biological processes, using random forest analysis, enrichment and variation analysis, and competing endogenous RNA (ceRNA) network analysis. Multiple immunofluorescence (mIF) and immunohistochemistry (IHC) were employed to characterize the existence of TLS and the expression of hub gene.ResultsTwo subclusters that enriched or depleted in TLS were identified. The two subclusters had distinct prognoses, clinical characteristics, and tumor immune infiltration. We established a TLS-related prognostic risk model including 14 genes and validated its predictive power in two external datasets. The model’s AUC values for 1-, 3-, and 5-year overall survival (OS) were 0.704, 0.737, and 0.746. The low-risk group had a superior survival rate, more abundant infiltration of immune cells, lower tumor immune dysfunction and exclusion (TIDE) score, and exhibited better immunotherapy efficacy. In addition, we selected the top important features within the model: VSIG4, SELL and PRRX1. Enrichment analysis showed that the hub genes significantly affected signaling pathways related to TLS and tumor progression. The ceRNA network: PRRX1-miRNA (hsa-miR-20a-5p, hsa-miR-485–5p) -lncRNA has been discovered. Finally, IHC and mIF results confirmed that the expression level of PRRX1 was markedly elevated in the TLS- CRC group.ConclusionWe conducted a study to thoroughly describe TLS gene signature in CRC. The TLS-related risk model was applicable for prognostic prediction and assessment of immunotherapy efficacy. The TLS-hub gene PRRX1, which had the potential to function as an immunomodulatory factor of TLS, could be a therapeutic target for CRC.

Abstract Metastatic colorectal cancer (mCRC) is a major cause of cancer-related mortality due to the absence of effective therapeutics. Thus, it is urgent to discover new drugs for mCRC. Fucosyltransferase 8 (FUT8) is a potential therapeutic target with high level in most malignant cancers including CRC. FUT8 mediates the core fucosylation of CD276 (B7-H3), a key immune checkpoint molecule (ICM), in CRC. FUT8-silence-induced defucosylation at N104 on B7-H3 attracts heat shock protein family A member 8 (HSPA8, also known as HSC70) to bind with 106-110 SLRLQ motif and consequently propels lysosomal proteolysis of B7-H3 through the chaperone-mediated autophagy (CMA) pathway. Then we report the development and characterization of a potent and highly selective small-molecule inhibitor of FUT8, named FDW028, which evidently prolongs the survival of mice with CRC pulmonary metastases (CRPM). FDW028 exhibits potent anti-tumor activity by defucosylation and impelling lysosomal degradation of B7-H3 through the CMA pathway. Taken together, FUT8 inhibition destabilizes B7-H3 through CMA-mediated lysosomal proteolysis, and FDW028 acts as a potent therapeutic candidate against mCRC by targeting FUT8. FDW028, an inhibitor specifically targeted FUT8, promotes defucosylation and consequent HSC70/LAMP2A-mediated lysosomal degradation of B7-H3, and exhibits potent anti-mCRC activities.

Abstract Background With the large-scale production and application of amorphous silica nanoparticles (aSiNPs), its adverse health effects are more worthy of our attention. Our previous research has demonstrated for the first time that aSiNPs induced cytokinesis failure, which resulted in abnormally high incidences of multinucleation in vitro, but the underlying mechanisms remain unclear. Therefore, the purpose of this study was firstly to explore whether aSiNPs induced multinucleation in vivo, and secondly to investigate the underlying mechanism of how aSiNPs caused abnormal cytokinesis and multinucleation. Methods Male ICR mice with intratracheal instillation of aSiNPs were used as an experimental model in vivo. Human hepatic cell line (L-02) was introduced for further mechanism study in vitro. Results In vivo, histopathological results showed that the rate of multinucleation was significantly increased in the liver and lung tissue after aSiNPs treatment. In vitro, immunofluorescence results manifested that aSiNPs directly caused microfilaments aggregation. Following mechanism studies indicated that aSiNPs increased ROS levels. The accumulation of ROS further inhibited the PI3k 110β/Aurora B pathway, leading to a decrease in the expression of centralspindlin subunits MKLP1 and CYK4 as well as downstream cytokines regulation related proteins Ect2, Cep55, CHMP2A and RhoA. Meanwhile, the particles caused abnormal co-localization of the key mitotic regulatory kinase Aurora B and the centralspindlin complex by inhibiting the PI3k 110β/Aurora B pathway. PI3K activator IGF increased the phosphorylation level of Aurora B and improved the relative ratio of the centralspindlin cluster. And ROS inhibitors NAC reduced the ratio of multinucleation, alleviated the PI3k 110β/Aurora B pathway inhibition, and then increased the expression of MKLP1, CYK4 and cytokinesis-related proteins, whilst NAC restored the clustering of the centralspindlin. Conclusion This study demonstrated that aSiNPs led to multinucleation formation both in vivo and in vitro. ASiNPs exposure caused microfilaments aggregation and inhibited the PI3k 110β/Aurora B pathway through excessive ROS, which then hindered the centralspindlin cluster as well as restrained the expression of centralspindlin subunits and cytokinesis-related proteins, which ultimately resulted in cytokinesis failure and the formation of multinucleation.

Abstract Background Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor, and its diagnosis is still a challenge. This study aimed to identify a novel bile marker for CCA diagnosis based on proteomics and establish a diagnostic model with deep learning. Methods A total of 644 subjects (236 CCA and 408 non-CCA) from two independent centers were divided into discovery, cross-validation, and external validation sets for the study. Candidate bile markers were identified by three proteomics data and validated on 635 clinical humoral specimens and 121 tissue specimens. A diagnostic multi-analyte model containing bile and serum biomarkers was established in cross-validation set by deep learning and validated in an independent external cohort. Results The results of proteomics analysis and clinical specimen verification showed that bile clusterin (CLU) was significantly higher in CCA body fluids. Based on 376 subjects in the cross-validation set, ROC analysis indicated that bile CLU had a satisfactory diagnostic power (AUC: 0.852, sensitivity: 73.6%, specificity: 90.1%). Building on bile CLU and 63 serum markers, deep learning established a diagnostic model incorporating seven factors (CLU, CA19-9, IBIL, GGT, LDL-C, TG, and TBA), which showed a high diagnostic utility (AUC: 0.947, sensitivity: 90.3%, specificity: 84.9%). External validation in an independent cohort (n = 259) resulted in a similar accuracy for the detection of CCA. Finally, for the convenience of operation, a user-friendly prediction platform was built online for CCA. Conclusions This is the largest and most comprehensive study combining bile and serum biomarkers to differentiate CCA. This diagnostic model may potentially be used to detect CCA.

Abstract The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

Abstract Human Epidermal Growth Factor Receptor-2 (HER2)-negative breast cancers (BCs) contain HER2-low and HER2-zero ones. HER2-low breast cancer has been receiving wide-spread concerns as the marvelous effect of novel anti-HER2 antibody-drug conjugates, however, the characteristic remains unknown. Our aim was to explore the differences of clinicopathological indicators and survival outcomes between HER2-low and HER2-0 breast cancers. We retrospectively analyzed 501 invasive breast cancer patients with complete data on HER2 status from 2017 to 2021 in our single center, of whom 415 HER2 negative patients were included for subsequent analysis. Each cohort was further divided into hormone receptor (HR) positive and HR negative subgroup. Clinicopathological factors and survival outcomes were collected and compared between HER2-low BCs and HER2-0 BCs. HER2-low BCs was obviously higher in HR positive BCs, with 277 (90.5%) HER2-low HR positive patients, 29 (9.5%) HER2-low HR negative patients, 68 (62.4%) HER2-0 HR positive patients and 41 (37.6%) HER2-0 HR negative patients (P

The microbial community diversity in huangjiu (yellow rice wine) vinasse during spontaneous fermentation into Xiangzao was analyzed by high-throughput sequencing. It turned out that the bacterial and fungal diversity was abundant. During the whole fermentation process, Proteobacteria was the dominant bacterial phylum, whose relative abundance ranged from 71.26% to 75.27%. The relative abundance of Firmicutes was 16.09% in the initial stage of fermentation and showed a downward trend in the middle and late stages. The dominant bacterial genera were Aquabacterium and Brevundimonas. The relative abundance of Aquabacterium was 22.48% at the beginning of fermentation, increased to 24.94% at the middle, and decreased to 21.29% at the end. Bacillus and Lactobacillus were also found during fermentation. The dominant phylum of fungi was Ascomycota, and its relative abundance decreased from 63.46% at the beginning of fermentation to 51.68% at the end. The dominant genus of fungi was Pichia, and its relative abundance ranged from 6.58% to 13.79%. Additionally, the relative abundance of Tausonia and Mortierella was above 3%. To sum up, the microbial community diversity is abundant during the spontaneous fermentation of huangjiu vinasse, and the fermentation process has a significant impact on the relative abundance of microorganisms.

Neutrophil infiltration has been linked to worse clinical outcomes after ischemic stroke. Microglia, a key type of immune-competent cell, engage in cross-talk with the infiltrating immune cells in the inflamed brain area, yet the molecular mechanisms involved remain largely unexplored. In this study, we investigated the mechanisms of how canonical transient receptor potential 1 (TRPC1) modulated neutrophil infiltration in male mouse cerebral ischemia and reperfusion injury (CIRI) models. Our findings revealed a notable upregulation of TRPC1 in microglia within both middle cerebral artery occlusion reperfusion (MCAO/R) and in vitro oxygen-glucose deprivation/regeneration (OGD/R) model. Conditional Trpc1 knockdown in microglia markedly reduced infarct volumes and alleviated neurological deficits. Microglia conditional Trpc1 knockdown mice displayed less neutrophil infiltration in peri-infarct area. Trpc1 knockdown microglia exhibited a reduced primed proinflammatory phenotype with less secretion of CC-Chemokines ligand (CCL) 5 and CCL2 after MCAO/R. Blocking CCL5/2 significantly mitigated neutrophil infiltration in microglia/neutrophil transwell co-culture system upon OGD/R condition. Trpc1 knockdown markedly reduced store-operated calcium entry and nuclear factor of activated T-cells c1 (NFATc1) level in OGD/R treated microglia. Overexpression of Nfatc1 reversed the CCL5/2 reducing effect of Trpc1 knockdown, which is mediated by small interfering RNA in BV2 cells upon OGD/R. Our data indicate that upregulation of TRPC1 in microglia stimulates the production of CCL5/2 through the Ca2+/NFATc1 pathway. Upregulated CCL5/2 leads to an increase in neutrophil infiltration into the brain, thereby aggravating reperfusion injury. Our results demonstrate the importance of TRPC1 in microglia-mediated neuroinflammation and suggest a potential means for reducing CIRI induced neurological injury.

In order to further improve the accuracy of synthetic speech detection, a synthetic speech detection method using texture feature based on circumferential local ternary pattern (CLTP) was proposed.The method extracted the texture information from the speech spectrogram using the CLTP and applied it as the feature representation of speech.The deep residual network was employed as the back-end classifier to determine the real or spoofing speech.The experimental results demonstrate that, on the ASVspoof 2019 dataset, the proposed method reduces the equal error rate (EER) by 54.29% and 2.15% respectively, compared with the traditional constant Q cepstral coefficient (CQCC) and linear predictive cepstral coefficient (LPCC), and reduced the EER by 17.14% compared with the local ternary pattern(LTP) texture features.The CLTP comprehensively takes into account the differences between the central and peripheral pixels in the neighborhood and between each peripheral pixel.Then it can acquire more texture information from the speech spectrogram, and improve the accuracy of synthetic speech detection.

Abstract Background Numerous studies have demonstrated that the high-order features (HOFs) of blood test data can be used to predict the prognosis of patients with different types of cancer. Although the majority of blood HOFs can be divided into inflammatory or nutritional markers, there are still numerous that have not been classified correctly, with the same feature being named differently. It is an urgent need to reclassify the blood HOFs and comprehensively assess their potential for cancer prognosis. Methods Initially, a review of existing literature was conducted to identify the high-order features (HOFs) and classify them based on their calculation method. Subsequently, a cohort of patients diagnosed with non-small cell lung cancer (NSCLC) was established, and their clinical information prior to treatment was collected, including low-order features (LOFs) obtained from routine blood tests. The HOFs were then computed and their associations with clinical features were examined. Using the LOF and HOF data sets, a deep learning algorithm called DeepSurv was utilized to predict the prognostic risk values. The effectiveness of each data set’s prediction was evaluated using the decision curve analysis (DCA). Finally, a prognostic model in the form of a nomogram was developed, and its accuracy was assessed using the calibration curve. Results From 1210 documents, over 160 blood HOFs were obtained, arranged into 110, and divided into three distinct categories: 76 proportional features, 6 composition features, and 28 scoring features. Correlation analysis did not reveal a strong association between blood features and clinical features; however, the risk value predicted by the DeepSurv LOF- and HOF-models is significantly linked to the stage. Results from DCA showed that the HOF model was superior to the LOF model in terms of prediction, and that the risk value predicted by the blood data model could be employed as a complementary factor to enhance the prognosis of patients. A nomograph was created with a C-index value of 0.74, which is capable of providing a reasonably accurate prediction of 1-year and 3-year overall survival for patients. Conclusions This research initially explored the categorization and nomenclature of blood HOF, and proved its potential in lung cancer prognosis.