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Abstract Multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are preferred for their high efficiency and high colour purity in organic light-emitting diodes (OLEDs). However, the design strategies of MR-TADF emitters in the red region are very limited. Herein, we propose a concept for a paradigm shift in orange-red/deep-red MR emitters by linking the outer phenyl groups in a classical MR framework through intramolecular sulfur (S) locks. Endowed with the planar architectural feature of the MR mother core, the proof-of-concept S-embedded emitters S-BN and 2S-BN also exhibit considerable flatness, which proves critical in avoiding the direct establishment of potent charge transfer states and inhibiting the non-radiative decay process. The emission maxima of S-BN and 2S-BN are 594 nm and 671 nm, respectively, and both have a high photoluminescence quantum yield of ~100%, a rapid radiative decay rate of around 107 s−1, and a remarkably high reverse intersystem crossing rates of about 105 s−1. Notably, maximum external quantum efficiencies of 39.9% (S-BN, orange-red) and 29.3% (2S-BN, deep-red) were also achieved in typical planar OLED structures with ameliorated efficiency roll-offs.

Probiotics have beneficial effects on improving egg quality, but there is little research about the effect of probiotics on metabolite composition, and the mechanisms are not yet fully understood. The aim of this study was to investigate the potential mechanisms by which compound Bacillus improves egg quality and metabolite composition. A total of 20,000 Jingfen No. 6 laying hens at 381 d old were randomly divided into two treatments: control group with a basal diet, and the basal diet with 5 × 108 CFU/kg compound Bacillus supplementation (Ba) group. The trial lasted eight weeks. The results showed that compound Bacillus improved the gloss and strength of eggshells and reduced the ratio of sand-shell eggs by 23.8%. Specifically, the effective layer of eggshell was thicker and its calcite column was closely connected. Compound Bacillus increased the contents of beneficial fatty acids in the egg yolk, and lipids and lipid-like molecules in the albumen (P

The finite element simulation method of bolt torsion under the tightening torque process was carried out,a quantitative relation between the tightening torque and the bolt preload was established for an actual structure.Firstly,the geometric model of the bolt with three⁃dimensional oblique thread was built,and the finite element mesh with thread was divided by using Hypermesh software,and the corresponding mechanical contact pairs were redefined.Then,Ansys Workbench software was used to apply the different sizes of tightening torque to the lower surface of the nut to obtain the magnitude of the corresponding axial force,so that the functional relation between the tightening torque and the bolt tension could be obtained.Finally,a bolt preload test was designed and the experimental,emulational and theoretical results were compared to verify the method.The results show that the results of the finite element simulation model are closer to the experimental results compared to the theoretical calculation results.The high⁃fidelity finite element model of bolt preload in this paper provides an important method for further accurate analysis of the bolt mechanics mechanism.

Objective Although smart senior care services offer numerous benefits, they have not yet gained widespread acceptance among the general populace, particularly seniors. Numerous related issues have surfaced, with the structural imbalance between supply and demand being most prominent. Currently, there is a lack of research distinguishing between the various categories of demand for smart ageing services and the associated behaviors of older individuals. In this study, we aimed to identify the types of demand and utilization of smart senior care services among Chinese older adults to understand their diverse characteristics and the factors that facilitate certain behaviors. We also analyzed the imbalance between supply and demand for smart senior care services and explored the factors influencing it, thereby providing a reference for optimizing smart senior services. Methods We conducted a cross-sectional study from January to March 2023 and analyzed 1037 valid questionnaires. Three types of smart senior care services were investigated: intelligent information, intelligent consultation, and intelligent monitoring. We identified the demand, utilization, and supply of these services among older individuals. Latent class analysis (LCA) was used to differentiate the heterogeneity of older adults in terms of service demand and utilization. Factors influencing service preferences were analyzed using binary logistic regression based on Andersen's behavioral model. Results Based on the LCA findings, service demand, and utilization were divided into two categories: positive demand (desire to use the services) or negative demand, and taking action or negative action to use the services. The persons with high demand but low utilization comprised the largest number of older people in this study (69.35%). The results indicated that the number of children (odds ratio (OR) = 1.491), community-provided smart devices (OR = 1.700), number of chronic diseases (OR = 1.218), and self-care capacity (OR = 0.214) are associated with positive demand. Meanwhile, pre-retirement employment, income sources, community device provided, community promotion, region, and self-care ability were significant predictors (p

BackgroundPrevious studies have shown that electrocardiographic (ECG) alarms have high sensitivity and low specificity, have underreported adverse events, and may cause neonatal intensive care unit (NICU) staff fatigue or alarm ignoring. Moreover, prolonged noise stimuli in hospitalized neonates can disrupt neonatal development. ObjectiveThe aim of the study is to conduct a nationwide, multicenter, large-sample cross-sectional survey to identify current practices and investigate the decision-making requirements of health care providers regarding ECG alarms. MethodsWe conducted a nationwide, cross-sectional survey of NICU staff working in grade III level A hospitals in 27 Chinese provinces to investigate current clinical practices, perceptions, decision-making processes, and decision-support requirements for clinical ECG alarms. A comparative analysis was conducted on the results using the chi-square, Kruskal-Wallis, or Mann-Whitney U tests. ResultsIn total, 1019 respondents participated in this study. NICU staff reported experiencing a significant number of nuisance alarms and negative perceptions as well as practices regarding ECG alarms. Compared to nurses, physicians had more negative perceptions. Individuals with higher education levels and job titles had more negative perceptions of alarm systems than those with lower education levels and job titles. The mean difficulty score for decision-making about ECG alarms was 2.96 (SD 0.27) of 5. A total of 62.32% (n=635) respondents reported difficulty in resetting or modifying alarm parameters. Intelligent module–assisted decision support systems were perceived as the most popular form of decision support. ConclusionsThis study highlights the negative perceptions and strong decision-making requirements of NICU staff related to ECG alarm handling. Health care policy makers must draw attention to the decision-making requirements and provide adequate decision support in different forms.

Pseudomonas aeruginosa is one of the leading causes of nosocomial infections worldwide and has emerged as a serious public health threat, due in large part to its multiple virulence factors and remarkable resistance capabilities. Stk1, a eukaryotic-type Ser/Thr protein kinase, has been shown in our previous work to be involved in the regulation of several signalling pathways and biological processes. Here, we demonstrate that deletion of stk1 leads to alterations in several virulence- and resistance-related physiological functions, including reduced pyocyanin and pyoverdine production, attenuated twitching motility, and enhanced biofilm production, extracellular polysaccharide secretion, and antibiotic resistance. Moreover, we identified AlgR, an important transcriptional regulator, as a substrate for Stk1, with its phosphorylation at the Ser143 site catalysed by Stk1. Intriguingly, both the deletion of stk1 and the mutation of Ser143 of AlgR to Ala result in similar changes in the above-mentioned physiological functions. Furthermore, assays of algR expression in these strains suggest that changes in the phosphorylation state of AlgR, rather than its expression level, underlie changes in these physiological functions. These findings uncover Stk1-mediated phosphorylation of AlgR as an important mechanism for regulating virulence and resistance in P. aeruginosa.

ObjectiveThis study aimed to investigate the relationship between bone metabolism markers, including serum klotho, fibroblast growth factor 23 (FGF23), 25(OH)D3, iPTH, calcium (Ca), and PHOS and the progression of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Additionally, the predictive value of these markers for DKD progression was evaluated.MethodsThis study involved 126 patients with T2DM between May 2021 and March 2023. DKD staging was assessed based on urinary protein excretion rates and estimated glomerular filtration rate (eGFR). The study evaluated serum concentrations of klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS across various stages and examined their relationships with clinical parameters. Receiver operating characteristic (ROC) curve analysis was utilized to determine the predictive accuracy of these bone metabolism markers for DKD. Multivariate linear and logistic regression analyses identified risk factors linked to DKD severity.ResultsAmong the 126 participants, 30 had non-DKD with normal proteinuria, while 96 had DKD, categorized as 31 with stage III DKD (microproteinuria), 34 with stage IV DKD, and 31 with stage V DKD (massive proteinuria). With advancing DKD from stage III to V, levels of klotho, 25(OH)D3, and Ca decreased significantly, whereas FGF23, iPTH and PHOS levels increased markedly. Klotho is significantly positively correlated with eGFR (r = 0.285, P = 0.001.) and negative correlations with serum creatinine (Scr) and UACR (r = -0.255, P = 0.004; r = -0.260, P = 0.011). FGF23 was positively related to systolic blood pressure (SBP) (r = 0.224, P = 0.012), but negatively with eGFR (r = -0.294, P = 0.001). Additionally, 25(OH)D3 exhibited significant negative correlations with several adverse clinical biomarkers, and both iPTH, Ca and PHOS were strongly associated with DKD progression (P

Klebsiella pneumoniae, an emerging multidrug-resistant pathogen, exhibits hypermucoviscosity (HMV) as a critical virulence trait mediated by its capsular polysaccharide (CPS). Recent discoveries have determined acetylation as a significant modification for CPS, although its impact on HMV and virulence was previously unknown. This study elucidates the roles of two enzymes: Klebsiella pneumoniae Acetylated CPS Esterase (KpACE), an esterase that removes acetyl groups from CPS, and WcsU, an acetyltransferase that adds acetyl groups to CPS. KpACE is highly upregulated in an ompR-deficient mutant lacking HMV, and its overexpression consistently reduces HMV and diminishes virulence in a mouse model of pneumonia. The esterase domain-containing KpACE effectively deacetylates model sugar substrates and CPS-K2. Site-directed mutagenesis of the conserved catalytic histidine residue at position 370 significantly reduces its enzymatic activity. This reduction correlates with decreased HMV, affecting key virulence traits including biofilm formation and serum resistance. Similarly, a deficiency in the wcsU gene abolishes CPS acetylation, and reduces HMV and virulence. These results highlight the importance of the delicate balance between CPS acetylation by WcsU and deacetylation by KpACE in regulating the pathogenicity of K. pneumoniae. Understanding this balance provides new insights into the modulation of virulence traits and potential therapeutic targets for combating K. pneumoniae infections.

Pneumococcal disease is caused by Streptococcus pneumoniae, including pneumonia, meningitis and sepsis. Capsular polysaccharides (CPSs) have been shown as effective antigens to stimulate protective immunity against pneumococcal disease. A major step in the production of pneumococcal vaccines is to prepare CPSs that meet strict quality standards in immunogenicity and safety. The major impurities come from bacterial proteins, nucleic acids and cell wall polysaccharides. Traditionally, the impurity level of refined CPSs is reduced by optimization of purification process. In this study, we investigated new aeration strategy and advanced sterilization methods by formaldehyde or β-propiolactone (BPL) to increase the amount of soluble polysaccharide in fermentation supernatant and to prevent bacterial lysis during inactivation. Furthermore, we developed a simplified process for the CPS purification, which involves ultrafiltration and diafiltration, followed by acid and alcohol precipitation, and finally diafiltration and lyophilization to obtain pure polysaccharide. The CPSs prepared from formaldehyde and BPL sterilization contained significantly lower level of residual impurities compared to the refined CPSs obtained from traditional deoxycholate sterilization. Finally, we showed that this novel approach of CPS preparation can be scaled up for polysaccharide vaccine production.

Objective: To evaluate the antiobesity effect and underlying mechanism of Andrias davidianus peptide (ADP) supplementation combined with treadmill exercise. Methods: A mouse model of obesity was established by feeding mice a high-fat diet (HFD), and the obese mice were randomly divided into four groups: model, treadmill exercise (Ex), ADP and ADP combined with treadmill exercise (ADP + Ex). The rats in the Ex group were subjected to a six-week treadmill exercise training. The rates in the ADP group were gavaged with ADP for six weeks. The rats in the ADP + Ex group were treated with ADP supplementation combined with treadmill exercise training. Normal Sprague Dawley (SD) rats were used as the control (CN) group. Body mass and food intake were recorded each week, and the serum levels of glucagon-like peptide-1 (GLP-1), neuropeptide Y (NPY), irisin, leptin, triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) were investigated by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of appetite-regulated proteins (NPY and proopiomelanocortin (POMC)) and energy metabolism-related proteins. Results: Body mass, inguinal and epididymal fat accumulation, food intake, and serum TG, TC and LDL levels significantly decreased in the ADP + Ex group compared with the model group. In addition, ELISA results revealed that combination of ADP supplementation with treadmill exercise reduced the serum levels of NPY and leptin but increased the serum concentrations of GLP-1 and irisin in obese rats. Western blot analysis showed that ADP supplementation combined with treadmill exercise greatly up-regulated the expression of POMC and energy metabolism related proteins (irisin, phospho-adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor γ co-activated factor-1α, and fibronectin type III domain containing protein 5), but down-regulated the expression of NPY. Conclusion: The combination of ADP with aerobic exercise can effectively alleviate HFD-induced obesity, thereby providing a new promising strategy to alleviate HFD-induced obesity.

Objective To reveal the sources and ecological risks of heavy metals in a typical lead-zinc mining area in Hebei Province, 156 soil samples were collected around a zinc mining area in Hebei Province through a systematic field sampling method. Methods The sources of heavy metals in the area were analysed via principal component analysis(PCA) and a positive matrix factorization(PMF) model. The risk assessment was carried out according to the index of geoaccumulation method and potential ecological risk index method. Results The results show that the mean values of Cr, Ni, Cu, Zn, As, Cd, Pb and Hg are 53.6, 25.7, 62.7, 692, 10.6, 1.75, 142, 0.129 mg/kg, respectively. Except for Cr, Ni and As, the other 5 elements present at different pollution levels. Above the background values of the soils in Hebei Province, the coefficient of variation of Hg, Cd, Zn, Pb and Cu is more than 1.75, and the coefficient of variation of As exceeds 0.5, indicating the high variability of these 6 elements. The results of the source analysis reveal that the main sources of soil heavy metals include mining activities, natural sources, agricultural activities, and gold smelting. Zn, Cd and Pb were mainly derived from mining activities; Cr and Ni were influenced by natural parent materials and were derived from natural sources; Cu was mainly derived from agricultural activities and mining activities; As was controlled by natural sources, mining activities and agricultural activities; and Hg was originated from mainly gold smelting and mining activities. The combination of PCA and the PMF model to corroborate each other facilitates the reliability of the heavy metal source analysis results. Conclusion There is anthropogenic Hg and Cd contamination in this area, as indicated by the high geoaccumulation indices and potential ecological risk indices. In addition, the ecological risk in general was found to be very high, and attention needs to be given to and management work to be carried out.

Aiming at the fatigue fracture problem of aireraft hydraulic pipeline connector, the fatigue life of hydraulic conduit with axial assembly deviation was predicted based on random vibration theory. Starting with the establishment of the finite element model of the pipeline connector of the real aircraft hydraulic system, the influence law of the assembly stress caused by the axial assembly deviation on the structure was analyzed, and the damping ratio of the pipeline connector under different axial deviation is obtained through the test. The random vibration analysis was carried out by using the finite element analysis software, and the stress response power spectral density function of the dangerous part was obtained. Combined with Miner linear damage theory, the random vibration fatigue life of the pipeline connector with assembly stress was predicted. The resonance fatigue test of pipeline was designed and carried out. It is found that the crack initiation position and the decreasing trend of fatigue life of pipeline are consistent with the simulation results. The simulation and test results show that when the axial deviation reaches 0.8 mm, it seriously affects the flight safety. The research results provide theoretical reference and technical support for the design and assembly theory of aviation hydraulic pipeline.

Objective: Molidustat is a novel agent investigated for the treatment of anemia in both dialysisdependent (DD) and non-dialysis-dependent (NDD) patients. Its efficacy and safety are still unclear. Methods: We searched five databases to identify randomized controlled trials comparing molidustat to erythropoiesis-stimulating agents (ESAs) or placebo in patients with anemia. Results: Six studies containing 2025 eligible participants were identified. For NDD patients, the change in Hb levels from baseline (ΔHb) was significantly higher for molidustat than for placebo [mean difference (MD) = 1.47 (95 % CI: 1.18 to 1.75), P

The zirconium alloy cladding of PWR fuel rods which undergo high neutron irradiation during service, will cause significant changes in its microstructure, thereby affecting its macroscopic performance. Therefore, the study of neutron irradiation behavior of zirconium alloy cladding is a focus of nuclear field. However, due to the strong radioactivity of materials after neutron irradiation, relevant experiments must be conducted in a hot cell. Therefore, research on the microstructure of irradiated fuel cladding is a difficult task. In this study, the microstructure of M5TM zirconium alloy cladding material after neutron irradiation was studied by means of transmission electron microscope in the hot cell facility of China Institute of Atomic Energy. The samples were from commercial pressurized water reactor AFA3G type spent fuel rods with burnup of 14 GW·d/tU and 41 GW·d/tU, respectively. A cladding sample with a length of about 10 mm from the fuel rod was cut, and the defueling and chemical cleaning in the hot cell were carried out to obtain a clean cladding sample. Then, mechanical sampling methods was used to prepare a thin slice sample of the cladding with 3 mm diameter. Finally, the electrolytic twin-jet thinning method was used to prepare the cladding transmission electron microscopy observation and analysis sample. In addition, to compare the structural changes of zirconium alloy cladding before and after irradiation, the same method was used to prepare un-irradiated observation and analysis samples of the same material. The observation and analysis results of the un-irradiated and irradiated samples reveal that there are native second phase particles (SPPs) inside the matrix structure of the un-irradiated zirconium alloy cladding, and the overall interior of the matrix is with few nano precipitates and no obvious dislocation structure observed. After irradiation, there is no significant difference in the size and distribution of the native SPPs in the matrix compared to the un-irradiated sample, but significant nano precipitates and high-density dislocation structures appear. As the fuel burnup increases, the size of nano precipitates increases. The similarity of dislocation structures between low and high burnup samples indicates that under the burnup of 14 GW·d/tU, the dislocation structures generated by irradiation in the zirconium alloy cladding basically reach saturation state. The results of selected area electron diffraction (SAED) indicate that although there are some amorphous structures in the native SPPs in the matrix after irradiation, the bcc crystal structure is still the main structure, indicating that the SPPs maintain certain irradiation stability at the burnup of 41 GW·d/tU. In addition, the EDS results of the SPPs indicate that with the increase of fuel burnup, the content of Nb element tends to be depleted. Analysis suggests that after neutron irradiation, the Nb atoms in the SPPs of zirconium alloy expand into the Zr matrix, promoting the precipitation of Nb elements in the form of nano Nb rich phases in the Zr matrix.

Abstract Background Previous studies have indicated that HBV pregenome RNA (HBV pgRNA) could predict HBeAg seroconversion among the chronic hapatitis B (CHB) patients treated with pegylated interferon (Peg-IFN) or nucleos(t)ide analogues (NAs). However, the data about the prediction of HBV pgRNA for spontaneous HBeAg seroconversion is limited. Methods One hundred thirteen CHB patients with HBeAg-positive in the immune active phase were followed up for 76 weeks without antiviral treatment. Based on the laboratory test results of liver function, HBeAg, anti-HBe, and HBV DNA at week 76, patients were assigned to two groups: spontaneous HBeAg seroconversion (group A, n = 18) and non-spontaneous HBeAg seroconversion group. Among the latter group, 36 patients were selected as controls (group B, n = 36). Results At week 12, between group A and group B, there was a significant difference in the level of HBV pgRNA (group A 6.35 ± 1.24 log10 copies/ml and group B 7.52 ± 0.79 log10 copies/ml, P = 0.001), and the difference enlarged at week 28. The receiver operating characteristic curves (AUROCs) of the HBV pgRNA level and the ∆HBV pgRNA at week 28 were 0.912 (P = 0.001, 95% CI: 0.830–0.994), and 0.934 (P = 0.001, 95% CI: 0.872–0.996), respectively. The optimal cutoffs of HBV pgRNA and the reduction from baseline (∆HBV pgRNA) at week 28 for spontaneous HBeAg seroconversion prediction were 5.63 log10 copies/ml and 1.85 log10 copies/ml, respectively. The positive predictive value and negative predictive value of HBV pgRNA and ∆HBV pgRNA at week 28 were 86.7% and 87.2%, 87.5% and 89.5%, respectively. And the combination of the HBV pgRNA level and the HBV pgRNA decreased could provide better prediction. Conclusions HBV pgRNA is a sound predictor for spontaneous HBeAg seroconversion among the CHB patients in immune active phase. Dynamic monitoring of HBV pgRNA is helpful for clinical treatment decision.

Abstract Background Pet cats frequently have diarrhea in their daily life. Bacillus has a protective role that has crucial beneficial functions on intestinal homeostasis. The aim of this research was to investigate the effects of the compound Bacillus on the prevention of diarrhea, microbiota and metabolism in pet cats. A total of 20 pet cats (1–2 years old, 3.91 ± 0.92 kg) were randomly divided into two groups and fed with a basal diet (Control group), or a basal diet supplemented with 3 × 109 CFU/kg compound Bacillus (Probiotics group). The experiment lasted 33 days. Results Results showed that the compound Bacillus significantly reduced the rate of soft stools and diarrhea in pet cats compared with the control group (P

Abstract Background Alternative splicing complexity plays a vital role in carcinogenesis and cancer progression. Improved understanding of novel splicing events and the underlying regulatory mechanisms may contribute new insights into developing new therapeutic strategies for colorectal cancer (CRC). Methods Here, we combined long-read sequencing technology with short-read RNA-seq methods to investigate the transcriptome complexity in CRC. By using experiment assays, we explored the function of newly identified splicing isoform TIMP1 Δ4-5. Moreover, a CRISPR/dCasRx-based strategy to induce the TIMP1 exon 4–5 exclusion was introduced to inhibit neoplasm growth. Results A total of 90,703 transcripts were identified, of which > 62% were novel compared with current transcriptome annotations. These novel transcripts were more likely to be sample specific, expressed at relatively lower levels with more exons, and oncogenes displayed a characteristic to generate more transcripts in CRC. Clinical outcome data analysis showed that 1472 differentially expressed alternative splicing events (DEAS) were tightly associated with CRC patients’ prognosis, and many novel isoforms were likely to be important determinants for patient survival. Among these, newly identified splicing isoform TIMP1 Δ4-5 was significantly downregulated in CRC. Further in vitro and in vivo assays demonstrated that ectopic expression of TIMP1 Δ4-5 significantly suppresses tumor cell growth and metastasis. Serine/arginine-rich splicing factor 1 (SRSF1) acts as a onco-splicing regulator through sustaining the inclusion of TIMP1 exon 4–5. Furthermore, CRISPR/dCasRx-based strategies designed to induce TIMP1 exon 4–5 exclusion have the potential to restrain the CRC growth. Conclusions This data provides a rich resource for deeper studies of gastrointestinal malignancies. Newly identified splicing isoform TIMP1 Δ4-5 plays an important role in mediating CRC progression and may be a potential therapy target in CRC.

Abstract Narrowband emissive multiple resonance (MR) emitters promise high efficiency and stability in deep‐blue organic light‐emitting diodes (OLEDs). However, the construction of ideal ultra‐narrow‐band deep‐blue MR emitters still faces formidable challenges, especially in balancing bathochromic‐shift emission, spectral narrowing, and aggregation suppression. Here, DICz is chosen, which possesses the smallest full‐width‐at‐half‐maximum (FWHM) in MR structures, as the core and solved the above issue by tuning its peripheral substitution sites. The 1‐substituted molecule Cz‐DICz is able to show a bright deep‐blue emission with a peak at 457 nm, an extremely small FWHM of 14 nm, and a CIE coordinate of (0.14, 0.08) in solution. The corresponding OLEDs exhibit high maximum external quantum efficiencies of 22.1%–25.6% and identical small FWHMs of 18 nm over the practical mass‐production concentration range (1–4 wt.%). To the best of the knowledge, 14 and 18 nm are currently the smallest FWHM values for deep‐blue MR emitters with similar emission maxima under photoluminescence and electroluminescence conditions, respectively. These discoveries will help drive the development of high‐performance narrowband deep‐blue emitters and bring about a revolution in OLED industry.

Background & aims: Necroptosis, a novel type of programmed cell death, is intricately associated with inflammatory response. Currently, most studies focus on the activation of necroptosis, while the mechanisms underlying the negative regulation of necroptosis remain poorly understood. Methods: The effects of sestrin2 (SESN2) overexpression or knockdown on the regulation of necroptosis were assessed in the TNFα/Smac-mimetic/Z-VAD-FMK (T/S/Z)-induced necroptosis model and palmitic acid (PA)-induced lipotoxicity model. Western-blot, co-Immunoprecipitation, Glutathione S-transferase pull-down, and confocal assays were employed to explore the regulatory mechanisms including protein–protein interactions and post-translational modification. Furthermore, we used GSK'872, a specific inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK) 3, to evaluate the relationship between SESN2-related alterations and RIPK3-mediated necroptosis in T/S/Z-induced necroptosis model, PA-induced lipotoxicity model, and high-fat high-cholesterol diet (HFHCD)-induced non-alcoholic steatohepatitis model. Results: Our findings revealed that SESN2 was upregulated under conditions that induce necroptosis and functioned as a negative regulator of necroptosis. High levels of SESN2 could equipped hepatocytes with the ability to defend against necroptotic inflammation and oxidative stress. Mechanistically, SESN2 interacted with RIPK3 and tuned down necroptosis by inhibiting the phosphorylation of RIPK3, promoting the ubiquitination of RIPK3, and preventing the formation of the RIPK1/RIPK3 necrosome. The depletion of SESN2 resulted in excessive necroptosis, accompanied by increased fat accumulation, inflammation, and oxidative stress in the experimental steatohepatitis model. Blocking necroptosis by GSK’872 reduced the liberation of pro-inflammatory cytokines and reactive oxygen species generation, but not hepatocyte fat deposition, in both PA-treated SESN2 knockout cells and HFHCD-fed SESN2 knockout mice, suggesting that the activation of RIPK3-mediated necroptosis may partially account for the hyperinflammation and excessive oxidative stress induced by SESN2 deficiency. Conclusion: Our results suggested that SESN2 inhibited RIPK3-mediated necroptosis; this regulation is an important for the immune homeostasis and the redox balance in the liver.

Abstract Background The etiology of nonalcoholic fatty liver disease (NAFLD) involves a complex interaction of genetic and environmental factors. Previous observational studies have revealed that higher leptin levels are related to a lower risk of developing NAFLD, but the causative association remains unknown. We intended to study the causal effect between leptin and NAFLD using the Mendelian randomization (MR) study. Methods We performed a two-sample Mendelian randomization (TSMR) analysis using summary GWAS data from leptin (up to 50,321 individuals) and NAFLD (8,434 cases and 770,180 controls) in a European population. Instrumental variables (IVs) that satisfied the three core assumptions of Mendelian randomization were selected. The TSMR analysis was conducted using the inverse variance weighted (IVW) method, MR-Egger regression method, and weighted median (WM) method. To ensure the accuracy and stability of the study results, heterogeneity tests, multiple validity tests, and sensitivity analyses were conducted. Results The findings of the TSMR correlation analysis between NAFLD and leptin were as follows: IVW method (odds ratio (OR) 0.6729; 95% confidence interval (95% CI) 0.4907–0.9235; P = 0.0142), WM method (OR 0.6549; 95% CI 0.4373–0.9806; P = 0.0399), and MR-Egger regression method (P = 0.6920). Additionally, the findings of the TSMR correlation analysis between NAFLD and circulating leptin levels adjusted for body mass index (BMI) were as follows: IVW method (OR 0.5876; 95% CI 0.3781–0.9134; P = 0.0181), WM method (OR 0.6074; 95% CI 0.4231–0.8721; P = 0.0069), and MR-Egger regression method (P = 0.8870). It has also been shown that higher levels of leptin are causally linked to a lower risk of developing NAFLD, suggesting that leptin may serve as a protective factor for NAFLD. Conclusions Using TSMR analysis and the GWAS database, we investigated the genetic relationship between elevated leptin levels and lowered risk of NAFLD in this study. However, further research is required to understand the underlying mechanisms.

This paper explores the application of network security technology within intelligent information terminals of the Internet of Things (IoT). It examines existing security issues and proposes a technical framework to address them. The technical framework starts from two aspects of data encryption and intrusion detection technology, in the data encryption technology, the CCA-ANC encryption algorithm is proposed to change the attacker in ANC from pure ciphertext attack to using the method of selective ciphertext attack. In intrusion detection technology, the DAGMM algorithm has been improved and optimized. The WEFS-DAGMM improved intrusion detection algorithm has been proposed, and an intrusion detection firewall has been constructed. In the performance test, the CCA-ANC encryption algorithm completes the encryption after inputting 1024MB of data in 13.6s, and the average speed of encryption reaches 71.54MB/s. The optimized WEFS-DAGMM algorithm achieves an accuracy of 0.952, which is 0.03 higher than the original DAGMM algorithm. The recall and F1 values are 0.03 higher than the original DAGMM algorithm, respectively. The algorithms have been improved by 0.03 and 0.037, respectively. Simulation experiments are conducted on the technical framework constructed in this paper. The success rate of malicious attack detection is greater than 90%, and the security protection rate reaches more than 99% in all of them.

Background: The emergence of multidrug-resistant tuberculosis (MDR-TB) in HIV-positive people poses a significant challenge to international efforts to eradicate tuberculosis (TB). Many studies found conflicting results when examining the correlation between HIV and MDR-TB. The purpose of the present investigation was to comprehensively review the literature on the association between HIV infection and MDR-TB in order to evaluate the impact of HIV on MDR-TB worldwide. Methods: Utilizing the databases PubMed, Scopus, Google Scholar, and ScienceDirect, studies published between January 2000 and March 2023 that are eligible for meta-analysis were selected. Using the random-effects model, the aggregated odds ratio of the empirical relationship between HIV and MDR-TB was calculated, along with a confidence interval ranging from 0 to 95 %. Examining the asymmetry of the funnel plot and utilizing Egger's and Begg's test, the possibility of publication bias was investigated. The extent of heterogeneity was determined using the I2 statistics. Results: Through a database search, we identified 1214 studies, from which we ultimately selected 15 studies involving 9667 patients. The odds ratio of 2.78 (95 % confidence interval: 1.07–7.20) between HIV/AIDS and MDR-TB indicates a significant positive correlation. Tau 2 = 3.46, chi 2 = 1440.46, df = 14, I2 = 99.0 %, z = 2.10, and p 0.05 indicate that there is substantial heterogeneity among pooled studies. Since I2 is 99 % (>50 %), a random effect model was employed. The percentage of multidrug-resistant HIV-positive patients across all included studies follows a normal distribution, as shown by a Box and whisker plot with a symmetric skewness and a mesokurtic tail and a scatter plot with a significant R2 value below 1 [R2 = 0.2476] showed the positive correlation between multidrug resistance and HIV infection. Conclusion: HIV infection increases MDR-TB risk, and the preceding pooled analysis showed an increased risk trend. Thus, MDR-TB, especially in HIV-positive patients, requires early case detection, quality-assured bacteriology diagnosis, and an effective infection control program.

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has a moderate treatment outcome. The traditional Chinese medicine KangXianYiAi formula (KXYA) has shown a clinically therapeutic effect on liver lesions. Here, we aimed to explore the effect and mechanism of KXYA in treating HCC. Methods: The rat HCC model induced with diethylnitrosamine was treated with KXYA. After treatment, the rat's serum and the liver tissues were used to detect biochemical indices and perform pathological examinations, second-generation sequencing (RNA-seq), and phosphoproteomics analysis (PPOA). The hepatoma cells were treated with KXYA in vitro and a nude-mice model. The expression levels of genes were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), Western blotting (WB), and immunohistochemistry approaches. The expression and prognosis data of genes in HCC were obtained from the public database. Results: Compared to the model, KXYA treatment significantly downregulated the rats’ serum hepatitis index, inflammatory damage, collagen deposition, and malignant proliferation of hepatocytes. And through the RNA-seq and PPOA analysis of rat liver tissues, we obtained the key pathways of KXYA including glutathione metabolism and ferroptosis. The qRT-PCR and WB results suggested that the key targets of UGDH, AKR1B10, and SLC7A11 were abnormally upregulated in HCC and downregulated to normal levels after KXYA treatment. In the public database, UGDH, AKR1B10, and SLC7A11 expression was significantly upregulated in HCC and indicated a poor prognosis. Discussion: Our study showed that KXYA treatment could effectively inhibit the progression of HCC by reducing glutathione and inducing ferroptosis of liver cancer cells.

Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4 h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo, with IC50 values of 1.943 μg/mL for dHAD-PTX and 1.874 μg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs.

Abstract Background This study aimed to investigate whether the combination of Macleaya cordata extract (MCE) and Bacillus could improve the laying performance and health of laying hens better. Methods A total of 360 29-week-old Jingbai laying hens were randomly divided into 4 treatments: control group (basal diet), MCE group (basal diet + MCE), Probiotics Bacillus Compound (PBC) group (basal diet + compound Bacillus), MCE + PBC group (basal diet + MCE + compound Bacillus). The feeding experiment lasted for 42 d. Results The results showed that the laying rate and the average daily egg mass in the MCE + PBC group were significantly higher than those in the control group (P

The ASP30 powder metallurgy (PM) high speed steels strengthened by TiCN were fabricated by powder metallurgy process, the effects of TiCN and rotary awaging deformation on the mechanical properties, microstructure, and tribological behaviors of the ASP30 steels were investigated. The results show that, adding TiCN with the mass fraction of 5% can effectively improve the wear resistance of ASP30. After the quenching-tempering treatment, the bending strength of ASP30+5%TiCN with the 56% swaging deformation is 4084.99 N·mm‒2, and the impact toughness is 14.55 J·cm‒2. The strength and toughness of the ASP30 steels after swaging are effectively improved. After the repeated radial swaging deformation, the TiCN phases are obviously broken and distribute as the dispersion particles. Besides, the rotary swaging can promote the formation of TiCN core-rim structure and improve the wettability and bonding ability between the hard phase and the matrix, inhibiting the generation of cracks between the hard phase and the matrix during grinding.

The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF’s function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice’s tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes’ expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3′, 4′, 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.

ABSTRACT Hypermucoviscosity is a hallmark of hypervirulent Klebsiella pneumoniae (hvKP). However, the molecular basis of its regulation is largely unknown. We hypothesize that hypermucoviscosity is modulated via two-component signal transduction systems (TCSs). In-frame deletion mutants of all 33 response regulators of hvKP ATCC43816 were generated using CRISPR/CAS and evaluated for their impacts on hypermucoviscosity. The response regulator OmpR is required for hypermucoviscosity in vitro and virulence in vivo in a mouse pneumonia model. The ΔompR mutant lost its mucoidy but retained its capsule level and comparable rmpADC expression, so transcriptomic analysis by RNA-Seq was performed to identify differentially expressed genes (DEGs) in ΔompR mutant. The top 20 Gene Ontology terms of 273 DEGs belong to purine ribonucleotide triphosphate biosynthetic and metabolic process, transmembrane transport, and amino acid metabolism. Among the overexpressed genes in the ΔompR mutant, the atp operon encoding F-type ATP synthase and the gcvTHP encoding glycine cleavage system were characterized further as overexpression of either operon reduced the mucoviscosity and increased the production of ATP. Furthermore, OmpR directly bound the promoter region of the atp operon, not the gcvTHP, suggesting that OmpR regulates the expression of the atp operon directly and gcvTHP indirectly. Hence, the loss of OmpR led to the overexpression of F-type ATP synthase and glycine cleavage system, which altered the energetic status of ΔompR cells and contributed to the subsequent reduction in the mucoviscosity. Our study has uncovered a previously unknown regulation of bacterial metabolism by OmpR and its influence on hypermucoviscosity. IMPORTANCE Hypermucoviscosity is a critical virulent factor for Klebsiella pneumoniae infections, and its regulation remains poorly understood at the molecular level. This study aims to address this knowledge gap by investigating the role of response regulators in mediating hypermucoviscosity in K. pneumoniae. We screened 33 response regulators and found that OmpR is essential for hypermucoviscosity and virulence of K. pneumoniae in a mouse pneumonia model. Transcriptomic analysis uncovered that genes involved in energy production and metabolism are highly upregulated in the ΔompR mutant, suggesting a potential link between bacterial energy status and hypermucoviscosity. Overexpression of those genes increased production of ATP and reduced mucoviscosity, recapitulating the ΔompR mutant phenotype. Our findings provide new insights into the regulation of K. pneumoniae hypermucoviscosity by a two-component signal transduction system, highlighting the previously unknown role of OmpR in regulating bacterial energy status and its influence on hypermucoviscosity.

IntroductionHepatic encephalopathy (HE) is a significant complication of cirrhosis, known to be associated with hospital readmission. However, few new serological indicators associated with readmission in HE patients have been identified and reported. The objective of our study was to identify simple and effective predictors reated to readmission in HE patients.Materials and methodsWe conducted a retrospective study at a single center on adult patients admitted with HE from January 2018 to December 2022. The primary endpoint was the first liver-related readmission within 30, 90, and 180 days, and we collected electronic medical records from our hospital for sociodemographic, clinical, and hospitalization characteristics. We utilized logistic regression analysis and multiple linear regression analysis to determine the predictors that were associated with the readmission rate and the length of the first hospitalization.ResultsA total of 424 patients were included in the study, among whom 24 (5.7%), 63 (14.8%), and 92 (21.7%) were readmitted within 30, 90, and 180 days, respectively. Logistic regression analysis showed that insurance status, alcoholic liver disease (ALD), ascites, the model for end-stage liver disease (MELD) score, and neutrophil-to-lymphocyte ratio (NLR) were significantly associated with 30-, 90-, and 180-day readmissions. Age and hepatocellular carcinoma (HCC) were predictors of 90- and 180-day readmissions. ALD was identified as a unique predictor of readmission in men, while hypertension was a predictor of 180-day readmission in women. Variceal bleeding, chronic kidney disease, and MELD score were associated with the length of the first hospitalization.ConclusionsNLR at discharge was identified as a significant predictor of 30-, 90- and 180-day readmissions in patients with HE. Our findings suggest that incorporating NLR into routine clinical assessments could improve the evaluation of the prognosis of liver cirrhosis.

Abstract Background Chemoattractant is critical to recruitment of osteoclast precursors and stimulates tumor bone metastasis. However, the role of chemoattractant in bone metastasis of colorectal cancer (CRC) is still unclear. Methods Histochemistry analysis and TRAP staining were utilized to detect the bone resorption and activation of osteoclasts (OCs) after administration of CCL7 neutralizing antibody or CCR1 siRNA. qRT-PCR analysis and ELISA assay were performed to detect the mRNA level and protein level of chemoattractant. BrdU assay and Tunel assay were used to detect the proliferation and apoptosis of osteoclast precursors (OCPs). The migration of OCPs was detected by Transwell assay. Western blots assay was performed to examine the protein levels of pathways regulating the expression of CCL7 or CCR1. Results OCPs-derived CCL7 was significantly upregulated in bone marrow after bone metastasis of CRC. Blockage of CCL7 efficiently prevented bone resorption. Administration of CCL7 promoted the migration of OCPs. Lactate promoted the expression of CCL7 through JNK pathway. In addition, CCR1 was the most important receptor of CCL7. Conclusion Our study indicates the essential role of CCL7-CCR1 signaling for recruitment of OCPs in early bone metastasis of CRC. Targeting CCL7 or CCR1 could restore the bone volume, which could be a potential therapeutical target. Video Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a liver disease associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and metabolic syndrome. The risk factors for NAFLD have not been identified. Metabolic dysfunction has been found to be an important factor in the pathogenesis and progression of NAFLD. However, the causal impact of blood metabolites on NAFLD is unclear.Methods: We performed a two-sample Mendelian randomization (MR) study. A genome-wide association study (GWAS) with 7824 participants provided data on 486 human blood metabolites. Outcome information was obtained from a large-scale GWAS meta-analysis of NAFLD, which contained 8,434 cases and 770,180 controls of Europeans. The inverse variance weighted (IVW) model was chosen as the primary two-sample MR analysis approach, followed by sensitivity analyses such as the heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. In addition, we performed replication, meta-analysis, and metabolic pathway analysis. We further conducted colocalization analysis to deeply reflect the causality.Results: After rigorous genetic variant selection, IVW, sensitivity analysis, replication, and meta-analysis, two known metabolites were identified as being associated with the development of NAFLD [biliverdin: OR = 1.45; 95% CI 1.20-1.75; p = 0.0001; myristoleate: OR = 0.57; 95% CI 0.39-0.83; p = 0.0030].Conclusion: By combining genomics with metabolomics, our findings provide a new perspective on the underlying mechanisms of NAFLD and have important implications for the screening and prevention of NAFLD.

Abstract Background Bone metastasis of colorectal cancer (CRC) often indicates a poor prognosis. Osteolysis can be observed in metastatic sites, implying an aberrant activation of osteoclasts. However, how osteoclastogenesis is regulated in metastatic microenvironment caused by colorectal cancer is still unclear. Methods In this study, mice bone metastatic model of CRC was established through injection of MC-38 or CT-26 cells. BrdU assays showed primary CD115 ( +) osteoclast precursors (OCPs) proliferated at the first 2 weeks. Transcriptomic profiling was performed to identify differentially expressing genes and pathways in OCPs indirectly co-cultured with CRC cells Results The expression of IL4Rα was found to be significantly upregulated in OCPs stimulated by tumor conditioned medium (CM). Further investigation indicated that IL-4 signaling regulated proliferation of OPCs through interacting with type I IL4 receptor, and neutrophils were the main source of IL-4 in bone marrow. The proliferation of OCPs can be inhibited in IL4 deficiency mice. In addition, ERK pathway was activated by IL4/IL4R signaling. Ravoxertinib, an ERK antagonists, could significantly prevent bone destruction through inhibiting the proliferation of OCPs. Conclusion Our study indicates the essential role of IL4/IL4R signaling for the proliferation of OCPs in early metastasis of CRC predominantly through activating ERK pathway, which remarkedly impacts the number of osteoclasts in later stage and leads to osteolytic lesions. Moreover, Ravoxertinib could be a new therapeutical target for bone metastasis of CRC.

This article will focus on the interpretation of a key concept in Chinese Neo-Confucianism of the Ming dynasty, namely that of xing 性. The concept is commonly translated as “nature” in Western languages, but this text will point out that there is a gap between the meaning of the Western concept “nature” and the Chinese concept 性. The main contribution of this paper is therefore to suggest a new method of interpreting Chinese philosophical concepts that bridges this gap. The method takes its inspiration from the hermeneutic theory of F. Schleiermacher. It consists, firstly, in re-placing the concept in its historical context—i.e. in the original “language area” where it assumes a meaning; secondly, in identifying the conceptual network which surrounds it, and thirdly, in determining the meaning of the concept in question by its relations to other concepts within the network. The end product of such a method is what we call the “semantic dictionary” of a concept. This article will give an example of how part of the meaning of 性 can be determined by its relations to another key Neo-Confucian concept, li 理.

This experiment investigated the effects of Bacillus amyloliquefaciens SC06 (BaSC06) and its combination with antimicrobial peptide (AMP) on the laying performance, egg quality, intestinal physical barrier, antioxidative status and immunity of commercial Jingbai strain laying hens. The results showed that BaSC06 significantly improved laying performance and egg quality of laying hens. However, there was a tendency to increase laying performance and decrease egg quality for the addition of AMP compared to the BaSC06 group. Also, both BaSC06 and its combination with AMP treatment increased length of microvilli and the content of tight junction protein in jejunum, and BaSC06 combination with AMP treatment is better than BaSC06 treatment alone. Compared to control, most of the serum antioxidant enzyme activities were significantly increased in the BaSC06+AMP group, the BaSC06 group only increased the activity of GSH-Px. Short-chain fatty acid analysis showed that BSC06 significantly increased the content of butyric, isobutyric and isovaleric acid in the cecum. However, the content of most of the short-chain fatty acids was even lower than that of the control group after the addition of AMP. Microbiota analysis showed that BaSC06 increased the absolute abundance of the butyrate-producing gut bacteria Ruminococaaoeae UCG-005, while the addition of AMP reduced the number of microorganisms detected and weakened the effect of BaSC06. BaSC06 acts as an anti-inflammatory agent by regulating the gut microbiota, and AMP further attenuates the immune response by reducing the number of gut microbes based on improved intestinal microbiota composition.

BackgroundDuring reactor operation, zirconium (Zr) alloy cladding is continuously oxidized as it gets in contact with fuel, and combines with the fuel to form a firm chemical interaction layer. This affects the thermal conductivity of the fuel gap, the mechanical properties of the cladding, and the mechanical interaction of the fuel cladding.PurposeThis work aims to obtain relevant analytical data on the chemical interaction layer between the irradiation Zr-alloy cladding and uranium oxide (UO2) pellets in a pressurized water reactor (PWR).MethodsFirst of all, the D13 intact fuel rod with a burnup of 45 GWd·tU-1 for PWRs in a nuclear power plant was chosen as UO2 pellets with a pellet enrichment of 4.45 wt%, and M5 Zr-alloy was used as the cladding materials. Then, a series of operations (cutting, pellet separation, inlaying, secondary cutting, inlaying, and polishing of cladding tubes) was conducted in the hot cell. The polished sample was transferred to the lead chamber and the UO2 fuel pellet was removed using 4 mol∙L-1 of nitric acid solution. The cladding tube was separated from the chemical interaction layer, and a low-speed cutter was used to cut the cladding tube to a width of 2~3 mm in the glove box. Finally, the morphology and structure of the chemical interaction layer were analyzed using metallographic microscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and hot cell Raman spectroscopy.ResultsThe analysis results show that the gap between the fuel pellet and cladding is approximately 14~19 μm after the fuel running to a burnup of 45 GWd·tU-1. In the chemical interaction layer, the time sequence of mechanical contact at different locations is different, resulting in discontinuity of the interaction layer. The SEM-EDS results show that the chemical interaction layer is in the shape of "worms" composed of U, Zr, and O to form a mixed phase (U,Zr)Ox compound.ConclusionsThe results of this study indicate that the chemical interaction layer is mainly composed of tetragonal zirconia (t-ZrO2) and monoclinic zirconia (m-ZrO2).

Spinal cord injury (SCI) causes severe neurological dysfunction leading to a devastating disease of the central nervous system that is associated with high rates of disability and mortality. Small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hucMSC-sEVs) have been explored as a promising strategy for treating SCI. In this study, we investigated the therapeutic effects of the intralesional administration of hucMSC-sEVs after SCI and determined the potential mechanisms of successful repair by hucMSC-sEVs. In vivo, we established the rat model of SCI. The Basso, Beattie, Bresnahan (BBB) scores showed that hucMSC-sEVs dramatically promoted the recovery of spinal cord function. The results of the hematoxylin–eosin (HE) staining, Enzyme-Linked Immunosorbent Assay (ELISA), and immunohistochemistry showed that hucMSC-sEVs inhibited inflammation and the activation of glia, and promoted neurogenesis. Furthermore, we studied the effect of hucMSC-sEVs on neural stem cells(NSCs) in vitro. We found that hucMSC-sEVs did not improve the migration ability of NSCs, but promoted NSCs to proliferate and differentiate via the ERK1/2 signaling pathway. Collectively, these findings suggested that hucMSC-sEVs promoted the functional recovery of SCI by activating neural stem cells via the ERK1/2 pathway and may provide a new perspective and therapeutic strategy for the clinical application of hucMSC-sEVs in SCI treatment.

High-performance glazing technologies are essential for achieving the occupant comfort and building energy efficiency required in contemporary and future buildings. In real-world applications, glazing façades are selected from a steadily increasing number of glazing technologies. However, the authors could not identify a systematic and comprehensive review and classification of glazing technologies in the literature. This creates a barrier when comparing typologically different glazing technologies and combining multiple technologies in a glazing unit. This paper provides a systematic review and classification of established and emerging glazing technologies based on publications from 2001–2022 which were interpreted following the PRISMA methodology. This study reveals that the majority of high-performance glazing systems used in practice are in multi-layer glazing configurations and that the glazing system performance can focus on including additional and multiple functionalities, which aim at improving overall building performance. It was also found that there is a large potential for improvement of multilayer, evacuated, aerogels, electrochromic, and solar cell glazing by incorporating other technologies or innovative materials in multi-layer glazing units for either improving existing technologies or for the development of new ones. However, their longevity, robustness, and cost affordability should be ensured.

Novel nereistoxin derivatives containing phosphonate were synthesized and characterized via 31P, 1H and 13C NMR and HRMS. The anticholinesterase activity of the synthesized compounds was evaluated on human acetylcholinesterase (AChE) using the in vitro Ellman method. Most of the compounds exhibited good inhibition of acetylcholinesterase. All of these compounds were selected to assess their insecticidal activity (in vivo) against Mythimna separata Walker, Myzus persicae Sulzer and Rhopalosiphum padi. Most of the tested compounds displayed potent insecticidal activity against these three species. Compound 7f displayed good activity against all three insect species, showing LC50 values of 136.86 μg/mL for M. separata, 138.37 μg/mL for M. persicae and 131.64 μg/mL for R. padi. Compound 7b had the highest activity against M. persicae and R. padi, with LC50 values of 42.93 μg/mL and 58.19 μg/mL, respectively. Docking studies were performed to speculate the possible binding sites of the compounds and explain the reasons for the activity of the compounds. The results showed that the compounds had lower binding energies with AChE than with the acetylcholine receptor (AchR), suggesting that compounds are more easily bound with AChE.

Q fever is a zoonotic infectious disease caused by Coxiella burnetii. The clinical symptoms of acute Q fever are usually atypical, and routine serological tests of C. burnetii are not readily available, making the diagnosis of Q fever a challenge. In this case, we report a male patient who had repeated fevers and was administered empirical anti-infective treatment, but the effect was poor. After conducting relevant laboratory and imagological examinations, the etiology has not yet been confirmed. Subsequently, metagenomic next-generation sequencing (mNGS) identified the sequence reads of C. burnetii from the patient's peripheral blood within 48 h, and then the diagnosis of acute Q fever was established. Moreover, the serological test of indirect immunofluorescence assay (IFA) of the C. burnetii antibody was further performed in the Centers for Disease Control, certifying the result of mNGS. The patient was ultimately treated with doxycycline and recovered well. mNGS is an unbiased and comprehensive method in infrequent or culture-negative pathogen identification. To our knowledge, this is the first case of acute Q fever identified by mNGS and confirmed by IFA in Taizhou, China. A further large-scale prospective clinical cohort study is worth carrying out to compare the diagnostic efficiency of mNGS with traditional serological methods and PCR in acute Q fever.

Abstract The acquired resistance of the first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a main factor leading to poor prognosis of non-small cell lung cancer (NSCLC), so we researched whether the high expression of hypoxia-inducible factor-1α (HIF-1α) in EGFR-TKIs sensitive NSCLC tissue tends to induce the acquired resistance. We detected the HIF-1α in normal lung tissue, EGFR-TKIs sensitive NSCLC tissue, the first generation EGFR-TKIs acquired resistant NSCLC tissue and acquired EGFR T790M mutation NSCLC tissue with the method of immunohistochemistry. Then, we compared the expression of HIF-1α in these tissues, and evaluate the effect of HIF-1α expression to the occurrence of acquired resistance. The expression of HIF-1α was much higher in the EGFR-TKIs sensitive NSCLC tissue than that in normal lung tissue. HIF-1α level became higher after the occurrence acquired resistance. There was negative correlation between HIF-1α level before receiving treatment and the time of acquired resistance occurring as well as the acquired EGFR T790M mutation occurring. As the treatment going on, EGFR-TKIs sensitivity rate of low HIF-1α level group was much higher than that of high level group. The high expression of HIF-1α related with the acquired resistance of the first generation EGFR-TKIs, and HIF-1α can be a biomarker to predict the early occurrence of acquired resistance.

Chidamide, a histone deacetylase (HDAC) inhibitor, displays antitumor activities in different tumor cells. Tongue squamous cell carcinoma (TSCC) is the most prevalent oral cavity malignancy with a high incidence and a high mortality rate. We describe the antitumor effects of chidamide on human TSCC SCC9 cells, which has not been reported before. Cell viability and wound healing assay and flow cytometry analysis were used to determine the proliferation, migration, cell cycle and apoptosis of chidamide-treated SCC9 cells in vitro. Western blotting was used to detect relative changes in protein levels. Our results reveal that chidamide inhibits SCC9 cell proliferation by decreasing ERK1/2 and mTOR phosphorylation and arresting the cell cycle in G0/G1 phase. Chidamide decreased cell migration in dose- and time-dependent manner by increasing E-cadherin expression. Chidamide induced SCC9 cells apoptosis by increasing the level of cleaved caspase-3 and decreasing the expression of Bcl-2. To sum up, chidamide displayed potent antitumor effects on SCC9 cells through multiple signaling pathways and has the potential to be developed as a new therapeutic agent to treat TSCC.

Abstract. Background:. Hepatitis C virus (HCV) genotype 3, particularly subtype 3b, is increasing in prevalence and distribution in China. This study evaluated the prevalence, regional distribution, clinical characteristics, host factors, treatment outcomes, and disease progression of patients with HCV genotype 3 in China. Methods:. A 5-year follow-up was preceded by a cross-sectional study. Treatment choices were at the discretion of treating physicians. Estimated infection time to overall-disease-progression (defined by ≥1 of: newly diagnosed cirrhosis; cirrhosis at baseline, Child-Turcotte-Pugh score increased 2 points or more; progression from compensated cirrhosis to decompensated cirrhosis; hepatocellular carcinoma; liver transplantation; or death) was calculated using the Kaplan-Meier method. Cox regression analyses were conducted to evaluate the risk factors for disease progression. Results:. The cross-sectional study enrolled 997 patients, including 91 with HCV genotype 3 infection. Among them, subtype 3b (57.1%) was more dominant than subtype 3a (38.5%). Five hundred and twelve patients were included into the follow-up phase. Among patients analyzed for estimated infection time to overall-disease-progression, 52/304 (17.1%) patients with HCV genotype 1 and 4/41 (9.8%) with HCV genotype 3 (4/26 with genotype 3b, 0/13 with genotype 3a, and 0/2 with undefined subtype of genotype 3) experienced overall-disease-progression. Patients with HCV genotype 3 were younger than those with genotype 1 (mean age: 39.5 ± 8.7 vs. 46.9 ± 13.6 years) and demonstrated more rapid disease progression (mean estimated infection time to overall-disease-progression 27.1 vs. 35.6 years). Conclusions:. HCV genotype 3, specifically subtype 3b, is associated with more rapid progression of liver disease. Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions. Trial registration:. NCT01293279, https://clinicaltrials.gov/ct2/show/NCT01293279; NCT01594554, https://clinicaltrials.gov/ct2/show/NCT01594554.

Abstract. Background:. Coronary heart disease (CHD) chronic heart failure has high morbidity and mortality, which poses a serious threat to patients’ quality of life and life safety. For the treatment of chronic heart failure of CHD, in addition to drugs, high quality nursing measures are also very important. Cluster nursing is a high-quality nursing model based on evidence-based evidence. There is no clinical study to evaluate the effect of cluster nursing on cardiac function and quality of life of CHD patients with chronic heart failure. Methods:. This is a prospective randomized controlled trial to investigate the effects of cluster nursing on cardiac function and quality of life in patients with CHD chronic heart failure. Approved by the Clinical Research Ethics Committee of our hospital, patients will be randomly assigned to either routine nursing or cluster nursing. They will be followed up for 3 months after 4 weeks of treatment. Observation indicators include: The total effective rate of cardiac function improvement, Minnesota Living with Heart Failure Questionnaire, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide, 6-minute walk test, adverse reaction, etc. Data were analyzed using the statistical software package SPSS version 25.0. Discussion:. This study will evaluate the effects of cluster nursing on cardiac function and quality of life of CHD patients with chronic heart failure. The results of this study will provide clinical basis for establishing reasonable and effective nursing programs for CHD patients with chronic heart failure.

Sarin is a potent organophosphorus nerve agent that causes cognitive dysfunction, but its underlying molecular mechanisms are poorly understood. In this study, a rat model of repeated low-level sarin exposure was established using the subcutaneous injection of 0.4 × LD50 for 21 consecutive days. Sarin-exposed rats showed persistent learning and memory impairment and reduced hippocampal dendritic spine density. A whole-transcriptome analysis was applied to study the mechanism of sarin-induced cognitive impairment, and a total of 1035 differentially expressed mRNA (DEmRNA), including 44 DEmiRNA, 305 DElncRNA, and 412 DEcircRNA, were found in the hippocampus of sarin-treated rats. According to Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Protein–Protein Interaction (PPI) analysis, these DERNAs were mainly involved in neuronal synaptic plasticity and were related to the pathogenesis of neurodegenerative diseases. The circRNA/lncRNA–miRNA–mRNA ceRNA network was constructed, in which Circ_Fmn1, miR-741-3p, miR-764-3p, miR-871-3p, KIF1A, PTPN11, SYN1, and MT-CO3 formed one circuit, and Circ_Cacna1c, miR-10b-5p, miR-18a-5p, CACNA1C, PRKCD, and RASGRP1 constituted another circuit. The balance between the two circuits was crucial for maintaining synaptic plasticity and may be the regulatory mechanism by which sarin causes cognitive impairment. Our study reveals the ceRNA regulation mechanism of sarin exposure for the first time and provides new insights into the molecular mechanisms of other organophosphorus toxicants.

The widespread use of wood preservatives, such as chromated copper arsenate (CCA), alkaline copper quaternary (ACQ), and copper azole (CA), may cause environmental pollution problems. Comparative studies on the effect of CCA-, ACQ-, and CA-treated wood on soil contamination are rarely reported, and the behavior of soil metal(loid) speciation affected by preservatives has been poorly understood. Soils under the CCA-, ACQ-, and CA-treated boardwalks were collected to investigate metal(loid) distribution and speciation at the Jiuzhaigou World Natural Heritage site. The results showed that the maximum mean concentrations of Cr, As, and Cu were found in soils under the CCA, CCA, and CCA plus CA treatments and reached 133.60, 314.90, and 266.35 mg/kg, respectively. The Cr, As, and Cu contamination in soils within a depth of above 10 cm was high for all types of boardwalks and limited in the horizontal direction, not exceeding 0.5 m. Cr, As, and Cu in soils were mainly present as residual fractions in all profiles and increased with depth. The proportion of non-residual As in soil profiles under CCA- and CCA plus CA-treatment and exchangeable Cu in CA- and CCA plus CA-treatment were significantly higher than those in the profiles under the other preservative treatments. The distribution and migration of Cr, As, and Cu within soils were influenced by the preservative treatment of trestles, in-service time of trestles, soil properties (e.g., organic matter content), geological disasters (e.g., debris flow), and elemental geochemical behavior. With the CCA treatment for trestles successively replaced by ACQ and CA treatments, the types of contaminants were reduced from a complex of Cr, As, and Cu to a single type of Cu, achieving a reduction in total metal content, toxicity, mobility, and biological effectiveness, thus reducing environmental risks.