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Background and Hypothesis The prognostic value of nutritional scoring tools in assessing the relationship between nutritional status and prognosis in hemodialysis patients is unclear. This multicenter retrospective cohort study compared the Prognostic Nutritional Index (PNI), Controlling Nutritional Status scores (CONUT), and Geriatric Nutritional Risk Index (GNRI) for predictive accuracy of all-cause and cardiovascular mortality, especially the impact of dynamic changes over time on prognosis.Methods Hemodialysis patients from four hospitals were included. Laboratory data and nutrition scores were collected at the initiation of dialysis, and at 6th, 12th, and 18th months after dialysis initiation. A joint model analyzed the relationship between dynamic nutritional scores and prognosis. Predictive values were assessed using the area under the curve (AUC).Results The study included 863 patients with a median follow-up of 37 months. During the follow-up, 23.8% of patients died, with 14% attributed to cardiovascular causes. Malnourished patients demonstrated higher risks for all-cause and cardiovascular mortality. Dynamic changes in PNI and GNRI scores were significantly associated with reduced all-cause and cardiovascular mortality risks. Precisely, longitudinal increases in PNI and GNRI scores corresponded to a 4% and 3% reduction in all-cause (PNI: HR, 0.96; 95% CI, 0.95–0.98; GNRI: HR, 0.97; 95% CI, 0.96–0.98) and cardiovascular mortality risk (PNI: HR, 0.96; 95% CI, 0.94–0.98; GNRI: HR, 0.97; 95% CI, 0.95–0.98) respectively, with longer dialysis duration. Changes in CONUT scores were not significantly associated with either all-cause or cardiovascular mortality. The AUCs of the three joint models indicated that the GNRI score (0.893) possessed higher predictive accuracy for all-cause mortality compared to PNI (0.832) and CONUT (0.852). Similar trends were observed for cardiovascular mortality.Conclusion Nutritional scores and their dynamic changes are intimately associated with mortality risk in hemodialysis patients. Compared to PNI and CONUT, the baseline GNRI and its post-dialysis variations demonstrate a superior predictive capability for all-cause and cardiovascular mortality in these patients.

In pursuit of reliable and efficient industrial microbes, this study integrates cutting-edge systems biology tools with Halomonas bluephagenesis TD01, a robust halophilic bacterium. We generated the complete and annotated circular genome sequence for this model organism, constructed and meticulously curated a genome-scale metabolic network, achieving striking 86.32% agreement with Biolog Phenotype Microarray data and visualize the network via an interactive Electron/Thrift server architecture. We then analyzed the genome-scale network using vertex sampling analysis (VSA) and found that productions of biomass, polyhydroxyalkanoates (PHA), citrate, acetate, and pyruvate are mutually competing. Recognizing the dynamic nature of H. bluephagenesis TD01, we further developed and implemented the hyper-cube-shrink-analysis (HCSA) framework to predict effects of nutrient availabilities and metabolic reactions in the model on biomass and PHA accumulation. We then, based on the analysis results, proposed and validate multi-step feeding strategies tailored to different fermentation stages. This integrated approach yielded remarkable results, with fermentation culminating in a cell dry weight of 100.4 g/L and 70% PHA content, surpassing previous benchmarks. Our findings exemplify the powerful potential of system-level tools in the design and optimization of industrial microorganisms, paving the way for more efficient and sustainable bio-based processes.

The paper presents a study on the fabrication of a lightweight acoustic hyperbolic paraboloid (HyPar) diaphragm using self-assembly nanoarchitectonics. The diaphragm is composed of a polyacrylonitrile (PAN) network combined with graphene oxide (GO) nanolayers. Spray coating is employed as a fabrication method, providing a simple and cost-effective approach to create large-scale curved diaphragms. The results demonstrate that the PAN/GO diaphragm exhibits acoustic performance comparable to a commercially available banana pulp diaphragm while significantly reducing weight and thickness. Notably, the graphene-based diaphragm is 15 times thinner and 8 times lighter than the commercial banana pulp diaphragm. This thinner and lighter nature of the graphene-based diaphragm offers advantages in applications where weight and size constraints are critical, such as in portable audio devices or acoustic sensors.

Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

ABSTRACTMitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells’ mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.

ABSTRACTThe increasing incidence of diseases caused by Coxsackievirus A6 (CV-A6) and the presence of various mutants in the population present significant public health challenges. Given the concurrent development of multiple vaccines in China, it is challenging to objectively and accurately evaluate the level of neutralizing antibody response to different vaccines. The choice of the detection strain is a crucial factor that influences the detection of neutralizing antibodies. In this study, the National Institutes for Food and Drug Control collected a prototype strain (Gdula), one subgenotype D1, as well as 13 CV-A6 candidate vaccine strains and candidate detection strains (subgenotype D3) from various institutions and manufacturers involved in research and development. We evaluated cross-neutralization activity using plasma from naturally infected adults (n = 30) and serum from rats immunized with the aforementioned CV-A6 strains. Although there were differences between the geometric mean titer (GMT) ranges of human plasma and murine sera, the overall trends were similar. A significant effect of each strain on the neutralizing antibody test (MAX/MIN 48.0 ∼16410.3) was observed. Among all strains, neutralization of the S112 strain by 15 different sera resulted in higher neutralizing antibody titers (GMTS112 = 132.0) and more consistent responses across different genotypic immune sera (MAX/MIN = 48.0). Therefore, S112 may serve as a detection strain for NtAb testing in various vaccines, minimizing bias and making it suitable for evaluating the immunogenicity of the CV-A6 vaccine.

Since carbon (C) atom has a variety of chemical bonds via hybridization between s and p atomic orbitals, it is well known that there are robust carbon materials. In particular, discovery of C60 has been an epoch making to cultivate nanocarbon fields. Since then, nanocarbon materials such as nanotube and graphene have been reported. It is interesting to note that C60 is soluble and volatile unlike nanotube and graphene. This indicates that C60 film is easy to be produced on any kinds of substrates, which is advantage for device fabrication. In particular, electron-/photo-induced C60 polymerization finally results in formation of one-dimensional (1D) metallic peanut-shaped and 2D dumbbell-shaped semiconducting C60 polymers, respectively. This enables us to control the physicochemical properties of C60 films using electron-/photo-lithography techniques. In this review, we focused on the structures, fundamental properties, and potential applications of the low-dimensional C60 polymers and other nanocarbons such as C60 peapods, wavy-structured graphene, and penta-nanotubes with topological defects. We hope this review will provide new insights for producing new novel nanocarbon materials and inspire broad readers to cultivate new further research in carbon materials.

ABSTRACTAdherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn’s disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.

As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.

With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide-resistance-associated mutations in MP sampled from paediatric patients in Southern China. Clinical data was collected from 1,33,674 patients admitted into investigational hospitals from 1 June 2017 to 30 November 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 paediatric patients for macrolide-resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of paediatric common respiratory infection diseases increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared to mNGS data between 2019–2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated that ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption during epidemic season and the severity of clinical outcomes in different scenarios.

Background Elderly hemodialysis (HD) patients have a high risk of death. The effect of different types of HD membranes on survival is still controversial. The purpose of this study was to determine the relationship between the use of low-flux or high-flux membranes and all-cause and cardiovascular mortality in elderly hemodialysis patients.Methods This was a retrospective clinical study involving maintenance hemodialysis patients which were categorized into low-flux and high-flux groups according to the dialyzer they were using. Propensity score matching was used to balance the baseline data of the two groups. Survival rates were compared between the two groups, and the risk factors for death were analyzed by multivariate Cox regression.Results Kaplan–Meier survival analysis revealed no significant difference in all-cause mortality between the low-flux group and the high-flux group (log-rank test, p = 0.559). Cardiovascular mortality was significantly greater in the low-flux group than in the high-flux group (log-rank test, p = 0.049). After adjustment through three different multivariate models, we detected no significant difference in all-cause mortality. Patients in the high-flux group had a lower risk of cardiovascular death than did those in the low-flux group (HR = 0.79, 95% CI, 0.54–1.16, p = 0.222; HR = 0.58, 95% CI, 0.37–0.91, p = 0.019).Conclusions High-flux hemodialysis was associated with a lower relative risk of cardiovascular mortality in elderly MHD patients. High-flux hemodialysis did not improve all-cause mortality rate. Differences in urea distribution volume, blood flow, and systemic differences in solute clearance by dialyzers were not further analyzed, which are the limitations of this study.

Methods In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model’s discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation.Results AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894–0.934) and 0.923 (95% CI, 0.895–0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model’s favorable clinical applicability.Conclusion We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

Objective This study aims to assess the clinical efficacy and safety of CHF-II in combination with RG for treating AKI on CKD (A on C), and to explore potential therapeutic mechanisms through lipidomics analysis.Methods 98 patients were enrolled and randomly assigned to the RG or RG + CHF groups. Both groups received RG therapy, with RG + CHF group additionally receiving CHF-II treatment over a duration of two weeks. Evaluation endpoints included changes in renal function, blood lipid profiles, urinary AKI biomarkers, and TCM symptoms before and after treatment. Serum samples were collected for lipid metabolite analysis.Results The total clinical effective rate in RG + CHF group was 73.5%, and that of RG group was 40.8%. TCM syndrome scores in RG + CHF group showed a more pronounced decrease (p

Objective To develop a diagnostic model for predicting occult uterine sarcoma in patients with presumed uterine fibroids.Materials and methods We retrospectively reviewed 41631 patients with presumed uterine fibroids who presented for HIFU treatment in 13 hospitals between November 2008 and October 2023. Of these patients, 27 with occult uterine sarcoma and 54 with uterine fibroids were enrolled. Univariate analysis and multivariate logistics regression analysis were used to determine the independent risk factors for the diagnosis of occult uterine sarcoma. A prediction model was constructed based on the coefficients of the risk factors.Results The multivariate analysis revealed abnormal vaginal bleeding, ill-defined boundary of tumor, hyperintensity on T2WI, and central unenhanced areas as independent risk factors. A scoring system was created to assess for occult uterine sarcoma risk. The score for abnormal vaginal bleeding was 56. The score for ill-defined lesion boundary was 90. The scores for lesions with hypointensity, isointensity signal/heterogeneous signal intensity, and hyperintensity on T2WI were 0, 42, and 93, respectively. The scores for lesions without enhancement on the mass margin, uniform enhancement of tumor, and no enhancement in the center of tumor were 0, 20, and 100, respectively. Patients with a higher total score implied a higher likelihood of a diagnosis of occult uterine sarcoma than that of patients with a lower score. The established model showed good predictive efficacy.Conclusions Our results demonstrated that the diagnostic prediction model can be used to evaluate the risk of uterine sarcoma in patients with presumed uterine fibroids.

Objective To develop a novel scoring system based on magnetic resonance imaging (MRI) for predicting the difficulty of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids.Materials and methods A total of 637 patients with uterine fibroids were enrolled. Sonication time, non-perfused volume ratio (NPVR), and ultrasound energy delivered for ablating 1 mm3 of fibroid tissue volume (E/V) were each classified as three levels and assigned scores from 0 to 2, respectively. Treatment difficulty level was then assessed by adding up the scores of sonication time, NPVR and E/V for each patient. The patients with score lower than 3 were categorized into low difficulty group, with score equal to or greater than 3 were categorized into high difficulty group. The potential predictors for treatment difficulty were compared between the two groups. Multifactorial logistic regression analysis model was created by analyzing the variables. The difficulty score system was developed using the beta coefficients of the logistic model.Results Signal intensity on T2WI, fibroid location index, largest diameter of fibroids, abdominal wall thickness, homogeneity of the signal of fibroids, and uterine position were independent influencing factors for the difficulty of USgHIFU for uterine fibroids. A prediction equation was obtained: difficulty score = 17 × uterine position (anteverted =0, retroverted =1)+71 × signal intensity (hypointense = 0, isointense/hyperintense = 1) +8 × enhancement (homogenous = 0, heterogeneous = 1)+25×(largest diameter of fibroids-20) +35 × (fibroid location index −0.2) +1×(abdominal wall thickness −5).Conclusions This scoring system established based on MRI findings can be used to reliably predict the difficulty level of USgHIFU treatment of uterine fibroids.

The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2− to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

The recently dominant SARS-CoV-2 Omicron JN.1 has evolved into multiple sublineages, with recurrent spike mutations R346T, F456L, and T572I, some of which exhibit growth advantages, such as KP.2 and KP.3. We investigated these mutations in JN.1, examining their individual and combined effects on immune evasion, ACE2 receptor affinity, and in vitro infectivity. F456L increased resistance to neutralization by human sera, including those after JN.1 breakthrough infections, and by RBD class-1 monoclonal antibodies, significantly altering JN.1 antigenicity. R346T enhanced ACE2-binding affinity and modestly boosted the infectivity of JN.1 pseudovirus, without a discernible effect on serum neutralization, while T572I slightly bolstered evasion of SD1-directed mAbs against JN.1's ancestor, BA.2, possibly by altering SD1 conformation. Importantly, expanding sublineages such as KP.2 containing R346T, F456L, and V1104L, showed similar neutralization resistance as JN.1 with R346T and F456L, suggesting V1104L does not appreciably affect antibody evasion. Furthermore, the hallmark mutation Q493E in KP.3 significantly reduced ACE2-binding affinity and viral infectivity, without noticeably impacting serum neutralization. Our findings illustrate how certain JN.1 mutations confer growth advantages in the population and could inform the design of the next COVID-19 vaccine booster.

Snow albedo is a key geophysical parameter that controls the energy exchanges between the atmosphere and Earth's surfaces and has been widely utilized in climatic and environmental change studies. However, recent studies have demonstrated that current albedo satellite products still have large uncertainties in snow-covered areas. In this study, we estimated the blue-sky shortwave albedo of snow surfaces using the eXtreme Gradient Boosting (XGBoost) algorithm with Moderate Resolution Imaging Spectroradiometer (MODIS) top-of-atmosphere (TOA) reflectance values, ERA-5 land reanalysis snow parameters (e.g., snow cover, snow density and snow depth water equivalent) and in situ measurements. In the XGBoost model, the MODIS MCD43 albedo values were input as prior knowledge, and the random sample validation results showed that the R2 and root mean square error (RMSE) values of this model were approximately 0.953 and 0.044, respectively. The typical sites for independent validation were subjected to in situ measurements at the UPE_L, AWS5, and CA_ARB sites. Finally, the retrieved XGBoost albedo values were compared with the official NASA MODIS (MCD43, collection 6), the Global Land Surface Satellite (GLASS), and the National Oceanic and Atmospheric Administration (NOAA) Visible Infrared Imaging Radiometer Suite (VIIRS) SURFALB albedo products. The validation results indicated that the proposed approach achieved much greater accuracy (RMSE = 0.052, bias = 0.002) than did the corresponding official MODIS (RMSE = 0.087, bias = −0.033), GLASS (RMSE = 0.089, bias = −0.031) and VIIRS SURFALB albedo (RMSE = 0.100, bias = −0.032) products. The improved shortwave albedo captured the rapid temporal changes in surface snow conditions.

The global health threat posed by carbapenem-resistant Klebsiella pneumoniae (CRKP) is exacerbated by the limited availability of effective treatments. Bacteriophages are promising alternatives to conventional antimicrobial agents. However, current phage databases are limited. Thus, identifying and characterizing new phages could provide biological options for the treatment of multi-drug resistant bacterial infections. Here, we report the characterization of a novel lytic phage, vB_KpnP_23, isolated from hospital sewage. This phage exhibited potent activity against carbapenemase-producing CRKP strains and was characterised by an icosahedral head, a retractable tail, and a genome comprising 40,987 base pairs, with a G + C content of 51 %. Capable of targeting and lysing nine different capsule types (K-types) of CRKP, including the clinically relevant ST11-K64, it demonstrated both high bacteriolytic efficiency and stability in various environmental contexts. Crucially, vB_KpnP_23 lacks virulence factors, antimicrobial resistance genes, or tRNA, aligning with the key criteria for therapeutic application. In vitro evaluation of phage-antibiotic combinations revealed a significant synergistic effect between vB_KpnP_23 and meropenem, levofloxacin, or amikacin. This synergy could lead to an 8-fold reduction in the minimum inhibitory concentration (MIC), suggesting that integrated treatments combining this phage with the aforementioned antibiotics may substantially enhance drug effectiveness. This approach not only extends the clinical utility of these antibiotics but also presents a strategic advance in combating antibiotic resistance. Specifically, it underscores the potential of phage-antibiotic combinations as a powerful tool in the treatment of infections caused by CRKP, offering a promising avenue to mitigate the public health challenges of antibiotic-resistant pathogens.

Wood and engineered wood products are green construction materials with excellent mechanical properties, widely utilized in various buildings and bridges. This paper reviews their short-term and long-term mechanical properties and probabilistic models. Short-term mechanical properties analysis reveals strong tensile (up to 165 MPa) and bending strengths (up to 264 MPa), contrasted by lower compressive strength (up to 103 MPa) and minimal shear/rolling strength (up to 14 MPa). These properties vary based on species type, lay-up angle, and dimensions, and are mutually influential. It also demonstrated that innovative techniques such as compression and cross-laminated lay-ups enhance the strength and sustainability of wood products, utilizing smaller logs effectively and reducing carbon emissions. For long-term mechanical properties, empirical models typically used for creep strength assessment fail to account for load duration variability, a gap partly addressed by damage accumulation models which require further development. The considerable time for long-term tests underlines the need for developing accelerated load tests to more effectively assess durability. As for probabilistic models, numerical methods and machine learning provide advanced probabilistic models by analyzing extensive data, offering significant improvements over traditional experimental methods.The global contribution of the work is mainly to enhance the understanding of wood and engineered wood products for properly design and extensive application of timber structures in civil engineering and promoting sustainable development.

ABSTRACT: The Parrot Borna virus 4 (PaBV-4) is the primary causative agent of parrot developmental disorder (PDD), leading to symptoms such as bloating, undigested feed in stool, decreased appetite, diarrhea, and weight loss. Its impact on the parrot industry has been significant, therefore, it is imperative to develop a rapid detection method for PaBV-4. The detection of PaBV-4 was achieved through the development of an RT-RAA assay, which involved the design of specific probes and primers targeting the N gene. This method allows for detection at 41°C within 30 min and has a minimum detection threshold of 8.56 × 101 copies/μL. The RT-RAA method demonstrated specific detection of PaBV-4 without any cross-reactivity observed with H5N6, H7N9, H9N2 avian influenza virus, newcastle disease virus (NDV), avian infectious bronchitis virus (IBV) and Parrot Borna virus 2 (PaBV-2). The coefficient of variation for the 3 repeatability experiments was below 10%. Tissue samples from 28 suspected cases of PaBV related deaths in parrots were analyzed using both RT-RAA and RT-qPCR methods. The sensitivity and specificity of both methods were 100%, demonstrating perfect agreement between them as indicated by a kappa value of 1. In conclusion, this study created a RT-RAA method for PaBV-4 detection successfully.

Prior research has reported mixed findings regarding the relationship between diversification and firm performance, because a diversification strategy produces not only synergies but also anti-synergies. We argue that information technology (IT) can help unlock the potential of diversification to enhance firm performance by maximising its synergistic effect while minimising its anti-synergistic effect. Using a sample of publicly listed Chinese firms on the Shanghai or Shenzhen Stock Exchange, we find that IT investment positively moderates the relationship between diversification and firm performance. Investing in IT contributes to greater coordination, control, information exchange, and cross-business knowledge sharing, which can enhance the synergistic effect of diversification and mitigate its anti-synergistic effect. Furthermore, we find that the moderating effect of IT investment on the relationship between diversification and firm performance is stronger for related diversification than unrelated diversification, indicating a greater need for IT when undertaking related (vs unrelated) diversification. These findings contribute to a more comprehensive understanding of the relationship between diversification and firm performance. Moreover, we advance research by showing that the moderating effect of IT on the relationship between diversification and firm performance varies according to diversification strategy.

Purpose Three‐level hybrid surgery (HS) consisting of cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) has been partly used for the treatment of multi‐level cervical degenerative disc disease (CDDD). The complications related to the implants and the collapse of the surgical vertebral bodies had been reported in multi‐level anterior cervical spine surgery. Thus, this study aimed to explore the biomechanical effects on the prostheses and vertebrae in three‐level HS. Methods A FE model of cervical spine (C0‐T1) was constructed. Five surgical models were developed. They were FAF model (ACDF‐CDA‐ACDF), AFA model (CDA‐ACDF‐CDA), FFF model (three‐level ACDF), SF model (single‐level ACDF), and SA model (single‐level CDA). A 75‐N follower load and 1.0‐N·m moment was applied to produce flexion, extension, lateral bending, and axial rotation. Results Compared with the intact model, the range of motion (ROM) of total cervical spine in FAF model decreased by 34.54%, 54.48%, 31.76%, and 27.14%, respectively, in flexion, extension, lateral bending, and axial rotation, which were lower than those in FFF model and higher than those in AFA model. The ROMs of CDA segments in FAF and AFA models were similar to the intact model and SA model. Compared with the intact model, the ROMs at C3/4 segment in FFF model increased from 5.71% to 7.85%, and increased from 5.31% to 6.81% at C7/T1 segment, following by FAF model, then the FAF model. The maximum interface pressures of the Prestige‐LP in FAF model were similar to SA model, however the corresponding values were increased in AFA model. The maximum interface pressures of the Zero‐P were increased in FAF and AFA model compared with those in SF and FFF models. The stress was mainly distributed on the screws. In AFA model, the maximum pressures of the ball and trough articulation in superior and inferior Prestige‐LP were all increased compared with those in SA and FAF model. In FFF model, the maximum pressures of the vertebrae were higher than those in other models. The stress was mainly distributed on the anterior area of the vertebral bodies. Conclusions HS seemed to be more suitable than ACDF for the surgical treatment of three‐level CDDD in consideration of the biomechanical effects, especially for the two‐level CDA and one‐level ACDF construct. But a more appropriate CDA prosthesis should be explored in the future.

Seed coat color affects the appearance and commodity quality of mung beans (Vigna radiata L.). The substances that affect mung bean seed coat color are mainly flavonoids, which have important medicinal value. Mapping the seed coat color gene in mung beans would facilitate the development of new varieties and improve their value. In this study, an F2 mapping population consisting of 546 plants was constructed using Jilv9 (black seed coat) and BIS9805 (green seed coat). Using bulk segregated analysis (BSA) sequencing and kompetitive allele-specific PCR (KASP) markers, the candidate region related to seed coat color was finally narrowed to 0.66 Mb on chromosome (Chr.) 4 and included eight candidate genes. Combined transcriptome and metabolome analyses showed that three of the eight candidate genes (LOC106758748, LOC106758747, and LOC106759075) were differentially expressed, which may have caused the differences in flavonoid metabolite content between Jilv9 and BIS9805. These findings can provide a research basis for cloning the genes related to seed coat color and accelerate molecular marker-assisted selection breeding in mung beans.

Abstract The volatilization of volatile organic compounds following a leakage event is a crucial mechanism that influences their migration and transformation in the soil. It is noteworthy that this process is intricately shaped by soil properties and environmental factors, exhibiting highly complex nonlinear relationships. However, there is currently no reliable mathematical model to predict the nonlinear relationship. To address this gap, the study conducted dynamic experiments considering various factors, including particle size, organic matter content, temperature, wind speed and moisture content. The volatilization rate ( $$k$$ k ), an important parameter in volatilization kinetics reflecting the speed of volatilization, was calculated by first-order kinetic principle. Finally, an innovative approach was introduced using a Back Propagation Neural Network (BPNN) model for prediction. The findings indicate that wind speed exerts the most significant impact on the volatilization rate of benzene among the examined factors. The application of BPNN demonstrates the model's accuracy in simulating benzene volatilization rates under diverse conditions. The results of K-fold cross-validation alleviate concerns of potential over-prediction, affirming the reliability of the constructed model. This research introduces a novel methodology for predicting volatilization parameters in real-world scenarios.

Abstract Background Dental caries is a common disease in the oral cavity, and the microorganisms in the cavity are colonized in the form of dental plaque biofilm. Streptococcus mutans is the main pathogen causing dental caries. Using probiotics to inhibit the growth and colonization of pathogenic bacteria, regulate mucosal immunity and improve oral microecological balance is an effective way to prevent or treat dental caries. The aim of this study was to evaluate the caries-prevention of probiotics in vitro and in rat caries models. Methods The probiotics used in this study are a combination of 4 strains of bacteria. After the fermentation of 4 strains (L. plantarum, L. salivarius, L. rhamnosus, and L. paracasei) was completed, they were mixed in equal volume proportions and used as samples to be tested. The mixture was then assessed the ability to inhibit the growth of S. mutans in vitro and in vivo. SPSS Statistics 22.0 (SPSS, Inc., Chicago, IL, USA) was used for analysis. Results In vitro the probiotics mixture could inhibit the growth of S. mutans and was able to remove biofilms formed by S. mutans. In a 42-day in vivo experiment, the probiotics group significantly reduced the level of S. mutans on the tooth surface of rats, reducing more than half the bacterial quantities compared with the caries model group (P

Abstract Anisotropic optical crystals can exhibit a hyperbolic response within the Reststrahlen band (RB) and support directional polaritonic propagations when interacting with light. Most of the reported low-symmetry optical crystals showcase the evolution from hyperbolic to elliptic dispersion topologies, largely owing to their adjacent RBs being either overlapped or separated. Here, we report an exceptional Reststrahlen point (ERP) in rare-earth oxyorthosilicate Y2SiO5, at which two neighboring RBs almost kiss each other. Consequently, we observe the direct hyperbolic-to-hyperbolic topological transition: the hyperbolic branches close and reopen along with the rotating transverse axis (TA). At such ERP, the TA merges to the direction orthogonal to its proximate phonon mode, mainly due to the interplay between these two non-orthogonal phonon modes. We also find that even with the existence of only one single RB, the TA can rotate in-plane. Our findings are prevalent in isostructural rare-earth oxyorthosilicates, such as Lu2SiO5. The universally underlying physics of ERP and its corresponding special class of rare-earth oxyorthosilicates may offer playgrounds for continuously tuning phonon polariton propagation direction, and broadband controlling light dispersion of polaritonic nanodevices.

Abstract Materials for radiation detection are critically important and urgently demanded in diverse fields, starting from fundamental scientific research to medical diagnostics, homeland security, and environmental monitoring. Low-dimensional halides (LDHs) exhibiting efficient self-trapped exciton (STE) emission with high photoluminescence quantum yield (PLQY) have recently shown a great potential as scintillators. However, an overlooked issue of exciton-exciton interaction in LDHs under ionizing radiation hinders the broadening of its radiation detection applications. Here, we demonstrate an exceptional enhancement of exciton-harvesting efficiency in zero-dimensional (0D) Cs3Cu2I5:Tl halide single crystals by forming strongly localized Tl-bound excitons. Because of the suppression of non-radiative exciton-exciton interaction, an excellent α/β pulse-shape-discrimination (PSD) figure-of-merit (FoM) factor of 2.64, a superior rejection ratio of 10−9, and a high scintillation yield of 26 000 photons MeV−1 under 5.49 MeV α-ray are achieved in Cs3Cu2I5:Tl single crystals, outperforming the commercial ZnS:Ag/PVT composites for charged particle detection applications. Furthermore, a radiation detector prototype based on Cs3Cu2I5:Tl single crystal demonstrates the capability of identifying radioactive 220Rn gas for environmental radiation monitoring applications. We believe that the exciton-harvesting strategy proposed here can greatly boost the applications of LDHs materials.

Abstract Methionine, an indispensable amino acid crucial for dietary balance, intricately governs metabolic pathways. Disruption in its equilibrium has the potential to heighten homocysteine levels in both plasma and tissues, posing a conceivable risk of inducing inflammation and detriment to the integrity of vascular endothelial cells. The intricate interplay between methionine metabolism, with a specific focus on S-adenosyl-L-methionine (SAM), and the onset of thoracic aortic dissection (TAD) remains enigmatic despite acknowledging the pivotal role of inflammation in this vascular condition. In an established murine model induced by β-aminopropionitrile monofumarate (BAPN), we delved into the repercussions of supplementing with S-adenosyl-L-methionine (SAM) on the progression of TAD. Our observations uncovered a noteworthy improvement in aortic dissection and rupture rates, accompanied by a marked reduction in mortality upon SAM supplementation. Notably, SAM supplementation exhibited a considerable protective effect against BAPN-induced degradation of elastin and the extracellular matrix. Furthermore, SAM supplementation demonstrated a robust inhibitory influence on the infiltration of immune cells, particularly neutrophils and macrophages. It also manifested a notable reduction in the inflammatory polarization of macrophages, evident through diminished accumulation of MHC-IIhigh macrophages and reduced expression of inflammatory cytokines such as IL1β and TNFα in macrophages. Simultaneously, SAM supplementation exerted a suppressive effect on the activation of CD4 + and CD8 + T cells within the aorta. This was evidenced by an elevated proportion of CD44- CD62L + naïve T cells and a concurrent decrease in CD44 + CD62L- effector T cells. In summary, our findings strongly suggest that the supplementation of SAM exhibits remarkable efficacy in alleviating BAPN-induced aortic inflammation, consequently impeding the progression of thoracic aortic dissection.

Abstract Actinide metallacyclic chemistry has been of interest due to its involvement in various chemical processes. However, fundamental understanding on the key species, actinide metallacyclic complexes, is limited to metallacyclopropenes whereas little is known about the actinide metallacyclopropynes presumably due to their unusual high reactivity. Herein, we report the preparation of a thorium metallacyclopropyne complex (η2-C ≡ C)ThCl3 – in the gas phase by using electrospray ionization mass spectrometry, and it is generated via a single-ligand strategy through sequential losses of CO2 and HCl from the monopropynoate precursor (HC ≡ CCO2)ThCl4 – upon collision-induced dissociation. Alternatively, the dual-ligand strategy involving consecutive losses of two CO2 and one C2H2 from the dipropynoate precursor (HC ≡ CCO2)2ThCl3 – works as well. According to the reactivity experiments and theoretical calculations, (η2-C ≡ C)ThCl3 – possesses a dianionic ligand C2 2– coordinated to the Th(IV) center in a side-on fashion. Further bonding analysis demonstrates the presence of a triple bond between the two C atoms, and the Th 5 f orbitals are significantly involved in the Th-(C ≡ C) bonding. A Th metallacyclopropyne structure is thus established for (η2-C ≡ C)ThCl3 –.

Abstract Background Leigh syndrome (LS) is a common mitochondrial disease caused by mutations in both mitochondrial and nuclear genes. Isoleucyl-tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine-tRNA synthetase, and variants in IARS2 have been reported to cause LS. However, the pathogenic mechanism of IARS2 variants is still unclear. Methods Two unrelated patients, a 4-year-old boy and a 5-year-old boy diagnosed with LS, were recruited, and detailed clinical data were collected. The DNA of the patients and their parents was isolated from the peripheral blood for the identification of pathogenic variants using next-generation sequencing and Sanger sequencing. The ClustalW program, allele frequency analysis databases (gnomAD and ExAc), and pathogenicity prediction databases (Clinvar, Mutation Taster and PolyPhen2) were used to predict the conservation and pathogenicity of the variants. The gene expression level, oxygen consumption rate (OCR), respiratory chain complex activity, cellular adenosine triphosphate (ATP) production, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (ROS) levels were measured in patient-derived lymphocytes and IARS2-knockdown HEK293T cells to evaluate the pathogenicity of the variants. Results We reported 2 unrelated Chinese patients manifested with LS who carried biallelic IARS2 variants (c.1_390del and c.2450G > A from a 4-year-old boy, and c.2090G > A and c.2122G > A from a 5-year-old boy), of which c.1_390del and c.2090G > A were novel. Functional studies revealed that the patient-derived lymphocytes carrying c.1_390del and c.2450G > A variants exhibited impaired mitochondrial function due to severe mitochondrial complexes I and III deficiencies, which was also found in IARS2-knockdown HEK293T cells. The compensatory experiments in vitro cell models confirmed the pathogenicity of IARS2 variants since re-expression of wild-type IARS2 rather than mutant IARS2 could rescue complexes I and III deficiency, oxygen consumption, and cellular ATP content in IARS2 knockdown cells. Conclusion Our results not only expand the gene mutation spectrum of LS, but also reveal for the first time the pathogenic mechanism of IARS2 variants due to a combined deficiency of mitochondrial complexes I and III, which is helpful for the clinical diagnosis of IARS2 mutation-related diseases.

Abstract Background Indoor environmental factors, such as pet ownership, presence of cockroaches, mattress quality, fuel usage (gas or electricity), use of biomass for cooking and heating, exposure to tobacco smoke or household molds can significantly affect the sleep quality of children with chronic cough. However, data regarding the effects of indoor environmental conditions on sleep in this population are limited. This study aimed to assess the prevalence of abnormal sleep behaviors and to establish associations between indoor environmental factors and sleep behaviors among children with chronic cough in Wuxi, China. Methods A cross-sectional design was employed in this study, involving children aged 3–18 years. Data on sociodemographic factors, allergies, home environmental exposures, and sleep characteristics of the participants were collected using paper-based questionnaires. The association between indoor environmental factors and sleep behaviors in children with chronic cough was analyzed using logistic regression models. Results The findings demonstrated that the prevalence of chronic cough among children in Wuxi was 15.50%. The chronic cough group exhibited a significantly higher incidence of eczema, wheezing, rhinitis, food allergy, and nasosinusitis than the non-chronic cough group. In addition, children with chronic cough also tended to have a family history of sleep disorders and adenoid hypertrophy (P

This is an article in the field of ceramics and composites. To achieve the resource utilization of fly ash and accurately assess the compressive strength of fly ash concrete, three predictive models for compressive strength were constructed using machine learning modeling techniques, including traditional linear regression, decision tree, and support vector machine models. These models were utilized to model and analyze the compressive performance of the concrete. Firstly, a corresponding experimental database was established, with seven input parameters including cement, fly ash, water reducer, coarse aggregate, fine aggregate, water, and curing age, and the compressive strength as the output parameter. Based on 10-fold cross-validation, the performance of the three models on the training set was evaluated using root mean square error (RMSE), mean absolute error, and correlation coefficient, and their performance on the test set was compared. The results showed that curing age had a high correlation with compressive strength (0.60), and the correlation of fly ash with compressive strength was higher than that of cement. The traditional linear regression model exhibited an RMSE of 7.27 and 5.91 on the training and test sets, respectively. The decision tree model showcased an RMSE of 2.72 and 9.23 on the respective sets, while the support vector machine model yielded an RMSE of 5.34 and 4.09. Overall, the support vector machine model exhibited good accuracy and robust performance in predicting the compressive strength of fly ash concrete. This research can provide strength design guidance for concrete using fly ash and promote the resource utilization of fly ash.

Abstract Background In China, retail pharmacies are critical sources for obtaining medications and play a vital role in residents’ daily access to drugs and treatment of common illnesses. Effectively guiding the placement of these pharmacies in areas of need through government regulation is crucial for enhancing medication access. In this study, we used population and retail pharmacy spatial distribution data from Shanghai to design guidance and supplementary methods for optimizing the spatial layout of retail pharmacies and medical insurance designated pharmacies based on regional characteristics. Methods Population distribution, road traffic network, administrative division and retail pharmacy data from Shanghai in 2018 were collected from relevant government departments. ArcGIS 10.3 was used to map the retail pharmacies and population distribution. Based on the spatial distribution of population and the service standards of pharmacies, service circles with insufficient pharmacies were identified, and supplementary methods for retail pharmacies and medical insurance designated pharmacies were developed. Results In 2018, Shanghai had 3009 retail pharmacies, each serving an average of 6412 residents. The city was divided into 2188 basic pharmaceutical service circles, each within a 15-minute walking distance. The results indicated that there were 1387 service circles without any pharmacies, 151 of which had populations exceeding 5000. Additionally, 356 service circles had pharmacies but lacked medical insurance designated ones. After supplementation, 841 retail pharmacies were planned to be added in residential areas. Compared with before, the coverage area and population served of the pharmacies increased significantly. Conclusions This study mapped the spatial distribution of population and retail pharmacies in Shanghai, and designed government guidance and supplementary methods for optimizing the layout of retail pharmacies. The findings offer valuable insights for government agencies in low- and middle-income countries to improve the spatial distribution of retail pharmacies.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). Here we present a new approach to treat MASH, termed “Fibrosis overexpression and retention (FORT)”. In this strategy, we design (1) retinoid-derivative lipid nanoparticle (LNP) to enable enhanced mRNA overexpression in fibrotic regions, and (2) mRNA modifications which facilitate anchoring of therapeutic proteins in ECM. LNPs containing carboxyl-retinoids, rather than alcohol- or ester-retinoids, effectively deliver mRNA with over 10-fold enhancement of protein expression in fibrotic livers. The carboxyl-retinoid rearrangement on the LNP surface improves protein binding and membrane fusion. Therapeutic proteins are then engineered with an endogenous collagen-binding domain. These fusion proteins exhibit increased retention in fibrotic lesions and reduced systemic toxicity. In vivo, fibrosis-targeting LNPs encoding fusion proteins demonstrate superior therapeutic efficacy in three clinically relevant male-animal MASH models. This approach holds promise in fibrotic diseases unsuited for protein injection.

To investigate the clinical characteristics, alcohol intake and risk factors of male patients with type 2 diabetes and coronary heart disease. 198 male patients with type 2 diabetes (T2DM) admitted to our hospital between October 2018 and January 2019 were selected as the T2DM group. 118 male patients with T2DM and coronary heart disease (CAD) admitted during the same period were selected as T2DM and CAD group. Collect the relevant clinical data of patients. The clinical characteristics of male patients with T2DM and CAD were analyzed using single factor analysis. An analysis of male patients’ risk factors for T2DM and CAD was conducted using binary logistic regression analysis. The risk probability model was constructed. Hosmer and Lemeshow were used to test the Goodness of fit of the probability model. ROC (receiver operating characteristic curve) curves were drawn with SPSS (Statistical Package For The Social Sciences) to evaluate the prediction model’s predictive value. T2DM with CAD patients were older, had longer diabetes duration, higher BMI (Body Mass Index), higher excess drinking proportion, higher hypertension proportion, higher LDL-C (Low-Density Lipoprotein Cholesterol) level, and higher FIB (Fibrinogen) than T2DM without CAD patients. Statistically significant differences were observed (p < 0.05). Age, BMI, diabetes duration, excessive drinking and hypertension are risk factors for coronary heart disease in male patients with T2DM. Compared with male patients with T2DM, male patients with T2DM and CAD are older, have longer durations of diabetes, have higher BMIs, excessive drinking and hypertension, and have higher levels of LDL-C and FIB. Age, BMI, diabetes duration, excessive drinking and hypertension are risk factors for male patients with T2DM and CAD. A clinical prognosis can be improved by giving early active intervention based on the risk situation of patients.

Abstract A novel approach is proposed to probe the nature of the double charm tetraquark through the prompt production asymmetry between $$T_{\bar{c}\bar{c}}^-$$ T c ¯ c ¯ - and $$T_{cc}^+$$ T cc + in pp collisions. When comparing two theoretical pictures, i.e. the compact tetraquark and hadronic molecular pictures, we find that the former one exhibits a significantly larger production asymmetry, enabling the unambiguous determination of the tetraquark’s internal structure. Additionally, distinctive differences in the transverse momentum and rapidity distributions of $$T_{\bar{c}\bar{c}}^-$$ T c ¯ c ¯ - and $$T_{cc}^+$$ T cc + cross sections emerge, particularly at $$p_\textrm{T}\approx 2~\textrm{GeV}$$ p T ≈ 2 GeV and $$y\approx \pm 6$$ y ≈ ± 6 at a center-of-mass energy of 14 $$~\textrm{TeV}$$ TeV . The insignificant asymmetry in hadronic molecular picture is because that hadronic molecules are produced in hadronic phase, where the phase space of their constituents needs to be taken into account rigorously. Our work can be extended to the exploration of other double heavy tetraquark candidates, offering a versatile approach to advance our understanding of exotic hadrons.

Purpose: To analyze the effect of right versus left long-term single-sided deafness (SSD) on sound source localization (SSL), discuss the necessity of intervention and treatment for SSD patients, and analyze the therapeutic effect of long-term unilateral cochlear implantation (UCI) from the perspective of SSL. Methods: This study included 25 patients with SSD, 11 patients with UCI, and 30 participants with normal hearing (NH). Their SSL ability was tested by obtaining their average root mean square (RMS) error values of SSL test. Results: The results showed that the RMS error value of SSD, UCI and NH groups were 52.26 ± 20.25°, 69.84 ± 12.14° and 4.27 ± 2.66°, respectively. The ability of SSL was better in the SSD-L group than that in the SSD-R group, and no significant difference existed in the SSD-R and the UCI group. Conclusion: When bilateral deafness patients select unilateral treatment, right-side cochlear implantation may be more beneficial in terms of SSL, which means that the central auditory cortex in long-term SSD patients is affected differently based on which side their deafness occurs.

Objective: To explore the application value and morphological characteristics of CT angiography (CTA) in the risk assessment of intracranial aneurysm rupture. Method: We included 82 patients with intracranial aneurysms from the Third Affiliated Hospital of Bengbu Medical College from October 2018 to October 2021. All study participants underwent CTA and digital subtraction angiography (DSA) examinations using Siemens 64 row 128 slice spiral CT and Siemens DSA machines. Statistical analyses were conducted on the condition of tumor rupture. The morphological characteristics of different tumor rupture cases, and the factors influencing intracranial aneurysm rupture were analyzed. Result: The rupture rate of 82 carotid artery patients in this group was 74.39% (61/82), and the non-rupture rate of the tumor was 25.61% (21/82). The number of sub-capsules (60.66%), area ratio, Size ration (SR), Aspect ratio (AR) and length of the ruptured aneurysm were greater than that of the unruptured aneurysm. The ruptured and unruptured aneurysms did not differ significantly in the incidence of single aneurysm (91.80%) and the distribution of aneurysms. Logistic regression analysis confirmed that area ratio, SR, AR, and tumor length were important risk factors for intracranial aneurysm rupture. Conclusion: CTA examination can clarify the morphological characteristics of intracranial aneurysms and evaluate the risk of tumor rupture.

Abstract The critical value of rock failure is determined by irreversible deformation (inelastic deformation, damage, and other internal dissipation) processes and external conditions before rock failure. Nevertheless, a thorough explanation of the mechanism causing cracks in rock material has not yet been provided. The strain energy theory is applied in this work to assess the initiation of rock cracks and investigate the relationship between energy digestion and rock strength. Firstly, the uniaxial compression test was conducted on sandstone samples under quasi-static loading conditions and the results of energy evolution, non-linear cumulative digestion, and stored ultimate energy were obtained. Then, a novel algorithm for assessing the initiation of rock cracks has been put forth. The concept of energy digestion index (EDI), which is the ratio of digested energy over the external loading energy, has been developed to characterize the energy absorption capacity of rock material. The result shows a relationship between the maximum growth rate of energy digestion and the increasing rate of variable elasticity modulus and crack initiation. The mechanical characteristics and peak strength of the rock material are negatively correlated with the EDI. By monitoring the digested energy status, an evaluation of the residual strength is introduced based on the relationships, which will initiate further research into in-situ monitoring and failure prediction.

Abstract Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Abstract Brain disease diagnosis using multiple imaging modalities has shown superior performance compared to using single modality, yet multi-modal data is not easily available in clinical routine due to cost or radiation risk. Here we propose a synthesis-empowered uncertainty-aware classification framework for brain disease diagnosis. To synthesize disease-relevant features effectively, a two-stage framework is proposed including multi-modal feature representation learning and representation transfer based on hierarchical similarity matching. Besides, the synthesized and acquired modality features are integrated based on evidential learning, which provides diagnosis decision and also diagnosis uncertainty. Our framework is extensively evaluated on five datasets containing 3758 subjects for three brain diseases including Alzheimer’s disease (AD), subcortical vascular mild cognitive impairment (MCI), and O[6]-methylguanine-DNA methyltransferase promoter methylation status for glioblastoma, achieving 0.950 and 0.806 in area under the ROC curve on ADNI dataset for discriminating AD patients from normal controls and progressive MCI from static MCI, respectively. Our framework not only achieves quasi-multimodal performance although using single-modal input, but also provides reliable diagnosis uncertainty.

Abstract IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.

Abstract Anion exchanger 3 (AE3) is pivotal in regulating intracellular pH across excitable tissues, yet its structural intricacies and functional dynamics remain underexplored compared to other anion exchangers. This study unveils the structural insights into human AE3, including the cryo-electron microscopy structures for AE3 transmembrane domains (TMD) and a chimera combining AE3 N-terminal domain (NTD) with AE2 TMD (hAE3NTD2TMD). Our analyzes reveal a substrate binding site, an NTD-TMD interlock mechanism, and a preference for an outward-facing conformation. Unlike AE2, which has more robust acid-loading capabilities, AE3’s structure, including a less stable inward-facing conformation due to missing key NTD-TMD interactions, contributes to its moderated pH-modulating activity and increased sensitivity to the inhibitor DIDS. These structural differences underline AE3’s distinct functional roles in specific tissues and underscore the complex interplay between structural dynamics and functional specificity within the anion exchanger family, enhancing our understanding of the physiological and pathological roles of the anion exchanger family.

Abstract Background Late-onset Pompe disease (LOPD) is mainly characterized by progressive limb-girdle muscle weakness and respiratory impairment, whereas stroke and cerebrovascular abnormalities have been insufficiently studied in LOPD. This study aimed to evaluate the frequency and pattern of intracranial artery and brain parenchyma abnormalities in LOPD patients. Results Neuroimaging data from 30 Chinese adult LOPD patients were collected from our center. Seven patients (7/30) had acute cerebral infarction or hemorrhage. Brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) revealed artery abnormalities in 23 patients (23/30). Dilative arteriopathy was found in 19 patients (19/30), with vertebrobasilar dolichoectasia found in 17 patients and dilatation of the anterior circulation arteries found in 8 patients. The maximum diameter of the basilar artery was correlated with disease duration (p

The design of auditorium chairs can directly reflect the image of public spaces. At present, the development of public furniture is relatively slow compared to household and office furniture. The design of auditorium chairs on the market is severely homogenized, relying on past experience and lacking scientific guidance. In order to create a better indoor public activity environment for users, from the perspective of user needs, first of all, 21 user needs for auditorium chairs were obtained through semi-structured interviews. Then, the Kano model was used to determine the attribute positioning of each demand. Finally, the FAST method was used to transform user demands into functions, assisting in the design optimization of hall chairs and promoting the future development of public furniture. The results indicate that the design of auditorium chairs must meet safety and stability, and the comfort and rechargeability of the seats are the most important needs of users. In the future, the functional design of auditorium chairs also needs to consider intelligent applications. The study applies a Kano-FAST integration method to the design innovation of auditorium chairs, providing data support for the development of furniture enterprise auditorium chairs and promoting product upgrading and optimization.

To reduce energy consumption, a new pulping process called A-D-E-RC (acidification/desalination/electrolysis/recycle-cooking) was developed by a research group in Guangxi University of China. The present work focuses on the step of recycle cooking (RC) to further investigate the technical feasibility of A-D-E-RC methods. Golden bamboo grass was considered as fiber source material for pulp, and it was cooked with the acidic treating of wastewater from black liquor. Then, the pulp obtained from each cooking was made into paper to test the changes in its physical properties. As a result, the pulp yield increased from 43.9% to 50.2%, after re-using acidified black liquor, and the paper's tear index and tensile index were improved. Therefore, this study demonstrated the feasibility of recycle cooking (RC) fiber materials for pulp applied the acidic treating wastewater from black liquor, and thereby, it further identifies the technical feasibility of A-D-E-RC pulping methods.

Abstract Wearable devices, such as data gloves and electronic skins, can perceive human instructions, behaviors and even emotions by tracking a hand's motion, with the help of knowledge learning. The shape or position single-mode sensor in such devices often lacks comprehensive information to perceive interactive gestures. Meanwhile, the limited computing power of wearable applications restricts the multimode fusion of different sensing data and the deployment of deep learning networks. We propose a perceptive fusion electronic skin (PFES) with a bioinspired hierarchical structure that utilizes the magnetization state of a magnetostrictive alloy film to be sensitive to external strain or magnetic field. Installed at the joints of a hand, the PFES realizes perception of curvature (joint shape) and magnetism (joint position) information by mapping corresponding signals to the two-directional continuous distribution such that the two edges represent the contributions of curvature radius and magnetic field, respectively. By autonomously selecting knowledge closer to the user's hand movement characteristics, the reinforced knowledge distillation method is developed to learn and compress a teacher model for rapid deployment on wearable devices. The PFES integrating the autonomous learning algorithm can fuse curvature-magnetism dual information, ultimately achieving human machine interaction with gesture recognition and haptic feedback for cross-space perception and manipulation.