The efficacy and safety of Bazi Bushen Capsule in treating premature aging: A randomized, double blind, multicenter, placebo-controlled clinical trial.

PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.

Enzyme-free and rapid colorimetric analysis of osteopontin via triple-helix aptamer probe coupled with catalytic hairpin assembly reaction.

BACKGROUND: Osteopontin (OPN) is closely associated with tumorigenesis, growth, invasion, and immune escape and it serves as a plasma biomarker for hepatocellular carcinoma (HCC). Nevertheless, the accurate and rapid detection of low-abundance OPN still poses significant challenges. Currently, the majority of protein detection methods rely heavily on large precision instruments or involve complex procedures. Therefore, developing a simple, enzyme-free, rapid colorimetric analysis method with high sensitivity is imperative. RESULTS: In this study, we have developed a portable colorimetric biosensor by integrating the triple-helix aptamer probe (THAP) and catalytic hairpin assembly (CHA) strategy, named as T-CHA. After binding to the OPN, the trigger probe can be released from THAP, then initiates the CHA reaction and outputs the signal through the formation of a G-quadruplex/Hemin DNAzyme with horseradish peroxidase-like activity. Consequently, this colorimetric sensor achieves visual free-labeled detection without additional fluorophore modification and allows for accurate quantification by measuring the optical density of the solution at 650 nm. Under optimal conditions, the logarithmic values of various OPN concentrations exhibit satisfactory linearity in the range of 5 pg mL-1 to 5 ng mL-1, with a detection limit of 2.04 pg mL-1. Compared with the widely used ELISA strategy, the proposed T-CHA strategy is rapid (∼105 min), highly sensitive, and cost-effective. SIGNIFICANCE: The T-CHA strategy, leveraging the low background leakage of THAP and the high catalytic efficiency of CHA, has been successfully applied to the detection of OPN in plasma, demonstrating significant promise for the early diagnosis of HCC in point-of-care testing. Given the programmability of DNA and the universality of T-CHA, it can be readily modified for analyzing other useful tumor biomarkers.

Molecular characterization of QTL for grain zinc and iron concentrations in wheat landrace Chinese Spring.

KEY MESSAGE: Three stable QTL for grain zinc concentration were identified in wheat landrace Chinese Spring. Favorable alleles were more frequent in landraces than in modern wheat cultivars. Wheat is a major source of dietary energy for the growing world population. Developing cultivars with enriched zinc and iron can potentially alleviate human micronutrient deficiency. In this study, a recombinant inbred line (RIL) population with 245 lines derived from cross Zhou 8425B/Chinese Spring was used to detect quantitative trait loci (QTL) for grain zinc concentration (GZnC) and grain iron concentration (GFeC) across four environments. Three stable QTL for GZnC with all favorable alleles from Chinese Spring were identified on chromosomes 3BL, 5AL, and 5BL. These QTL explaining maxima of 8.7%, 5.8%, and 7.1% of phenotypic variances were validated in 125 resequenced wheat accessions encompassing both landraces and modern cultivars using six kompetitive allele specific PCR (KASP) assays. The frequencies of favorable alleles for QGZnCzc.caas-3BL, QGZnCzc.caas-5AL and QGZnCzc.caas-5BL were higher in landraces (90.4%, 68.0%, and 100.0%, respectively) compared to modern cultivars (45.9%, 35.4%, and 40.9%), suggesting they were not selected in breeding programs. Candidate gene association studies on GZnC in the cultivar panel further delimited the QTL into 8.5 Mb, 4.1 Mb, and 47.8 Mb regions containing 46, 4, and 199 candidate genes, respectively. The 5BL QTL located in a region where recombination was suppressed. Two stable and three less stable QTL for GFeC with favorable alleles also from Chinese Spring were identified on chromosomes 4BS (Rht-B1a), 4DS (Rht-D1a), 1DS, 3AS, and 6DS. This study sheds light on the genetic basis of GZnC and GFeC in Chinese Spring and provides useful molecular markers for wheat biofortification.

Enhancing diabetic wound healing with a pH/glucose dual-responsive hydrogel for ROS clearance and antibacterial activity.

Currently, the treatment of diabetic wounds in clinical practice is still unsatisfactory due to the risks of oxidative damage and bacterial infection during the healing process. An optimal wound dressing should exhibit robust capabilities in scavenging reactive oxygen species (ROS) and combatting bacterial growth. In this study, we utilized borax as a crosslinker and prepared a pH/glucose dual-responsive composite hydrogel based on poly(vinyl alcohol) (PVA), sodium alginate (SA), and tannic acid (TA). This hydrogel, loaded with cerium dioxide, serves as an effective ROS scavenger, promoting wound closure by reducing the level of ROS in the wound area. Additionally, the hydrogel can release the antibacterial drug ofloxacin in response to the low pH and high glucose microenvironment in infected wounds. Results from skin defect model in diabetic mice demonstrated this ROS-scavenging and antibacterial hydrogel can suppress inflammation and accelerate wound healing. In summary, our work provides a new perspective on a local and stimulus-responsive drug delivery strategy for treating diabetic wounds.

[Outcomes of idiopathic pulmonary fibrosis patients with high body mass index undergoing extracorporeal membrane oxygenation support].

OBJECTIVE: To evaluate the extracorporeal membrane oxygenation (ECMO) related outcomes during hospitalization during the intensive care unit (ICU) in idiopathic pulmonary fibrosis (IPF) patients with high body mass index (BMI, > 25 kg/m2) undergoing lung transplantation with ECMO support. METHODS: A retrospective observational study was conducted. IPF patients who received ECMO during lung transplantation admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from 2019 to 2020 were enrolled. Preoperative indicators including, demographics, comorbidities, arterial blood gas, and laboratory indicators; intraoperative indicators, such as lung lobe volume reduction, surgical type, surgical time, cold ischemia time, blood loss and transfusion volume; immediate indicators upon admission to the ICU, such as blood gas analysis and laboratory indicators; ECMO related outcomes, such as ECMO mode, ECMO support time, ECMO related complications (bleeding at the catheterization site, intraductal thrombosis, lower limb ischemia), and the length of ICU stay, duration of mechanical ventilation, and 30-day survival rate were collected. According to BMI, patients were divided into three groups: light weight group (BMI < 18.5 kg/m2), normal weight group (BMI 18.5-24.9 kg/m2), and overweight group (BMI ≥ 25.0 kg/m2). Mainly to compare the relevant outcomes of ECMO among patients during ICU. RESULTS: A total of 114 IPF patients who received ECMO support during lung transplantation were collected, including 23 cases in the light weight group, 63 cases in the normal weight group, and 28 cases in the overweight group. Compared with patients with underweight and normal weight, overweight patients were more likely to have hypertension (46.4% vs. 8.7%, 23.8%, P < 0.01) and coronary heart disease (32.1% vs. 4.3%, 20.6%, P < 0.05) before surgery, which was consistent with international guidelines for obesity. Other clinical data (preoperative, intraoperative, ICU characteristics) showed no statistically significant differences and were comparable. There was no statistically significant difference in terms of ECMO related outcomes, such as ECMO related complications [veno-venous (V-V) mode: 78.3%, 77.8%, 78.6%, veno-arterial (V-A) mode: 21.7%, 22.2%, 21.4%], ECMO support time (hours: 61.70±20.03, 44.57±5.76, 41.77±7.26), ECMO related complications (bleeding at the catheterization site: 4.3%, 7.9%, 14.3%; intraductal thrombosis: 8.7%, 12.7%, 17.9%; lower limb ischemia: 8.7%, 12.7%, 14.3%), and the length of ICU stay (days: 11±3, 7±1, 9±1), duration of mechanical ventilation [days: 2 (2, 11), 2 (2, 6), 3 (2, 8)] among the light weight group, normal weight group, and overweight group (all P > 0.05). Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 30-day cumulative survival rate among the three groups (Log-Rank test: χ 2 = 0.919, P = 0.632). CONCLUSIONS: High BMI does not worsen ECMO-related outcomes or adversely affect early prognosis in IPF patients undergoing lung transplantation. BMI as a single parameter should not be a contraindication for the use of ECMO in lung transplantation surgery for IPF patients.

Impact of inter-lesion distance and first-pass isolation on outcomes of pulmonary venous isolation for paroxysmal atrial fibrillation.

BACKGROUND: Contiguity of ablation lesions is a critical determinant of success for paroxysmal atrial fibrillation (PAF) ablation. Evidence supports maintaining an inter-lesional distance (ILD) ≤ 6 mm during pulmonary venous isolation (PVI). Meanwhile, first-pass isolation (FPI) on PVI outcome in follow-up was not deeply studied. The impact of ILD and FPI on PAF ablation outcomes was investigated. METHODS: Consecutive PAF patients who underwent first-time antral PVI were recruited. Coordinates of ablation points were extracted from the electro-anatomical mapping system and analyzed using custom-developed software to determine the ILD. A gap is defined as ILD greater than 6 mm. FPI was defined as the achievement of PVI by encircling the ipsilateral veins while simultaneously recording their electrical activity using a multipolar catheter. The primary endpoint was freedom from documented atrial arrhythmias including AF, atrial tachycardia (AT), or atrial flutter (AFL) lasting longer than 30 s during follow-up. RESULTS: A total of 105 patients underwent first-time antral PVI. During 13.3 ± 0.6 months of follow-up, atrial arrhythmias recurrence was noted in 22.9% of the patients. Atrial arrhythmia recurrence was significantly higher in patients with more gaps (> 2) (37.0% versus 11.9%, P < 0.01), and the number of gaps was an independent predictor of AF/AT/AFL recurrence. (Hazard ratio [HR] 1.20, 95% CI 1.03-1.40, P = 0.02). The group with FPI for at least one ipsilateral pair of PVs exhibited a decreased number of gaps (2.0 versus 7.0, P < 0.01) and demonstrated a significant correlation with a reduction of recurrence (HR 0.26, 95% CI 0.09-0.71, P = 0.01). Among 16 patients who underwent repeat ablation, the number of gaps during the index PVI was associated with PV reconnection (PVR) (P < 0.01). CONCLUSIONS: Gaps created during PVI are a modifiable determinant of AF/AT/AFL recurrence, and avoidance of gaps is crucial to improve clinical outcomes of PAF ablation. In addition, FPI exhibited a strong predictive capability for clinical success in patients with PAF.

Parameter calibration of discrete element model for gluten densification molding.

The densified powder material is convenient for storage and transportation, with broad market application prospects. In this study, the discrete element model parameters required for simulating gluten densification were calibrated using the Hertz-Mindlin with JKR contact model. Initially, physical testing techniques were utilized to assess the size distribution, density, and angle of repose (AoR) of gluten particles. Following this, the Plackett-Burman test, the steepest ascent test, and the Box-Behnken test were conducted, and the significant factors were obtained: The coefficient of rolling friction (P-P) was 1.038, the coefficient of static friction (P-P) was 0.071, and the surface energy (P-P) was 0.047. Finally, the AoR and densification simulations were performed under the optimal parameter combination, along with validation tests. The results showed that the relative error between the simulated and tested AoR was 0.52%. The compression ratio and compression force curves of simulated and actual were similar.

Impact of Geko Neuromuscular Stimulator on Preoperative Preparation in Ankle Fractures.

OBJECTIVE: To explore the impact of the Geko neuromuscular stimulator on preoperative preparation in patients with ankle fractures. STUDY DESIGN: Quasi-experiment study. Place and Duration of the Study: Department of Foot and Ankle Surgery and Department of Orthopaedics, Beijing Tongren Hospital, Capital Medical University, Beijing, China, between December 2020 and 2021. METHODOLOGY: This quasi-experiment study included patients with ankle fractures treated with Geko neuromuscular stimulator before surgical fixation. The primary outcome was limb swelling at 24, 48, and 72 hours (h) after admission, and the secondary outcomes were pain according to visual analogue scale (VAS) at 12, 24, and 48 hours after admission, preoperative waiting time, and comfort 4 and 72 h after admission. RESULTS: A total of 60 patients were included in the study; 30 in the conventional treatment group (mean age 41.16 ± 2.01 years) and 30 in the Geko group (mean age 40.22 ± 2.68 years). The limb swelling in patients was significantly different between the Geko and conventional treatment groups (p = 0.004). Besides, the swelling values at 48 (p < 0.001) and 72 (p < 0.001) hours were significantly lower than those at 24 hours. The pain in patients was significantly different between the Geko and conventional treatment groups (p = 0.007). Besides, the swelling values at 24 (p < 0.001) and 48 (p < 0.001) hours are significantly lower than those at 24 hours. Comfort was significantly higher at 4 h (69.54 ± 2.18 vs. 67.22 ± 3.14, p = 0.002) and 72 h [(88.50 (84.00 - 94.00) vs. 82.14 ± 3.08, p < 0.001)] after admission. The preoperative waiting time (3.52 ± 1.8 vs. 5.15 ± 2.1 hours, p = 0.002) was significantly shorter in the Geko group. CONCLUSION: The Geko neuromuscular stimulator is a useful option for preoperative preparation in patients with ankle fractures to reduce local swelling and pain and improve patients' comfort. KEY WORDS: Ankle fractures, Lower extremity, Neuromuscular stimulator, Peroneal nerve, Pain.

Optimization of N fertilizer and synergistic intercropping to enhance the productivity advantage of faba bean and effective control of chocolate spot epidemics.

Intercropping of wheat/faba bean is a common practice within the legume-cereal family. However, the benefits of nitrogen (N) fertilizer optimized synergistic intercropping in improving faba bean productivity while controlling the prevalence of chocolate spot disease have not been established. This study conducted continuous field experiments spanning two planting seasons to investigate two key findings. (1) Optimizing N fertilizer application can enhance the productivity of intercropped faba bean. (2) The percentage severity index (PSI) during the period of maximum prevalence rate (Rmax) of faba bean chocolate spot disease, poses a substantial challenge to faba bean yield. The results indicated that the land equivalent ratio and transgressive overyielding index for each intercropping treatment increased with higher N fertilizer application, exceeding a value of 1, and the land saving proportion also exceeded 0. Intercropping primarily enhances productivity, as measured by the harvest index (HI), by amplifying the complementary effect rather than the selection effect, thus improving the net benefit of intercropping. The HI of single and intercropped faba bean increased with the N1 and N2 treatments in both planting seasons. However, the HI of single and intercropped faba bean at the N3 level decreased significantly, ranging from 17.85% to 29.62%. Furthermore, a notable negative correlation was established between the PSI during critical epidemic (initial epidemic, maximum epidemic rate, and late epidemic) periods and observed and expected faba bean yields. As PSI increased, faba bean yields decreased and PSI of intercropping at different periods were lower than those observed in the single cropping. Additionally, intercropping with the optimized N fertilizer treatment (N2 treatment) exhibited an enhanced relative control effect on chocolate spot disease in faba bean, ranging from 35.21% to 52.36%. This finding confirmed the productivity advantage of intercropping faba bean. In conclusion, this study suggested that optimizing N fertilizer application can enhance the productivity of intercropped faba bean. Wheat/faba bean intercropping effectively controlled the PSI during the period of Rmax, which would otherwise threaten faba bean yield. Consequently, this practice ensured sustained advantages of wheat/faba bean intercropping.

Complete mitochondrial genome data and phylogenetic analysis of Papilio macilentus Janson, 1877 (Lepidoptera: Papilionoidea: Papilionidae).

In the present study, the complete mitochondrial genome (mitogenome) of the Papilio macilentus (Lepidoptera: Papilionoidea: Papilionidae) was sequenced by next-generation sequencing method. The mitochondrial genome is a circular DNA molecule of 15,264 bp in size with 80.7% AT content, including 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes), and a long non-coding region (Control region). All protein-coding genes are initiated by ATN codons, and terminated with TAA, TAG, or single T. All tRNAs can be folded into common clover leaf secondary structure, except trn-S1. Phylogenetic analyses based on 13 protein-coding genes and 2 rRNA genes using maximum likelihood and Bayesian inference confirmed that P. macilentus and Papilio memnon are clustered into a clade, and revealed the relationships between Papilionini, Troidini, Teinopaippini and Leptocircini.

Chlorogenic acid improves the development of porcine parthenogenetic embryos by regulating oxidative stress and ameliorating mitochondrial function.

Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 µM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

CMOS Scaling for the 5 nm Node and Beyond: Device, Process and Technology.

After more than five decades, Moore's Law for transistors is approaching the end of the international technology roadmap of semiconductors (ITRS). The fate of complementary metal oxide semiconductor (CMOS) architecture has become increasingly unknown. In this era, 3D transistors in the form of gate-all-around (GAA) transistors are being considered as an excellent solution to scaling down beyond the 5 nm technology node, which solves the difficulties of carrier transport in the channel region which are mainly rooted in short channel effects (SCEs). In parallel to Moore, during the last two decades, transistors with a fully depleted SOI (FDSOI) design have also been processed for low-power electronics. Among all the possible designs, there are also tunneling field-effect transistors (TFETs), which offer very low power consumption and decent electrical characteristics. This review article presents new transistor designs, along with the integration of electronics and photonics, simulation methods, and continuation of CMOS process technology to the 5 nm technology node and beyond. The content highlights the innovative methods, challenges, and difficulties in device processing and design, as well as how to apply suitable metrology techniques as a tool to find out the imperfections and lattice distortions, strain status, and composition in the device structures.

Deficiency of P2RY11 causes narcolepsy and attenuates the recruitment of neutrophils and macrophages in the inflammatory response in zebrafish.

Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses.

Hydrophobic core evolution of major histocompatibility complex class I chain-related protein A for dramatic enhancing binding affinity.

Interface residues at sites of protein-protein interaction (PPI) are the focus for affinity optimisation. However, protein hydrophobic cores (HCs) play critical roles and shape the protein surface. We hypothesise that manipulating protein HCs can enhance PPI interaction affinities. A cell stress molecule, major histocompatibility complex class I chain-related protein A (MICA), binds to the natural killer group 2D (NKG2D) homodimer to form three molecule interactions. MICA was used as a study subject to support our hypothesis. We redesigned MICA HCs by directed mutagenesis and isolated high-affinity variants through a newly designed partial-denature panning (PDP) method. A few mutations in MICA HCs increased the NKG2D-MICA interaction affinity by 325-5613-fold. Crystal structures of the NKG2D-MICA variant complexes indicated that mutagenesis of MICA HCs stabilised helical elements for decreasing intermolecular interactive free energy (ΔG) of the NKG2D-MICA heterotrimer. The repacking of MICA HC mutants maintained overall surface residues and the authentic binding specificity of MICA. In conclusion, this study provides a new method for MICA redesign and affinity optimisation through HC manipulation without mutating PPI interface residues. Our study introduces a novel approach to protein manipulation, potentially expanding the toolkit for protein affinity optimisation.

Rapid quantitative analysis of petroleum coke properties by laser-induced breakdown spectroscopy combined with random forest based on a variable selection strategy.

Driven by the "double carbon" strategy, petroleum coke short-term demand is growing rapidly as a negative electrode material for artificial graphite. The analysis of petroleum coke physicochemical properties has always been an important part of its research, encompassing significant indicators such as ash content, volatile matter and calorific value. A strategy based on laser-induced breakdown spectroscopy (LIBS) in combination with chemometrics is proposed to realize the rapid and accurate quantification of the above properties. LIBS spectra of 46 petroleum coke samples were collected, and an original random forest (RF) calibration model was constructed by optimizing the pretreatment parameters. The RF calibration model was further optimized based on variable importance measures (VIM) and variable importance in projection (VIP) methods. After variable selection, the elemental spectral lines related to ash content, volatile matter and calorific value modeling were screened out, thus initially exploring the correlation between these properties and elements. Under the optimized spectral pretreatment method, VI threshold and model parameters, the mean relative error (MREP) of the prediction set of ash content, volatile matter and calorific value were 0.0881, 0.0527 and 0.006, the root mean square error (RMSEP) of the prediction set of ash content, volatile matter and calorific value were 0.0471%, 0.6178% and 0.2697 MJ kg-1, respectively, and the determination coefficient (RP2) of the prediction set was 0.9187, 0.9820 and 0.9510, respectively. The combination of LIBS technology and chemometric methods can provide powerful technical means for the analysis and evaluation of the physicochemical properties of petroleum coke.

Association of the systemic immune-inflammation index with anemia: a population-based study.

Background: Inflammation has been reported to be related to anemia. As a novel inflammatory marker, Systemic immune-inflammation index (SII) has not been studied with Anemia. The aim of this study was to investigate the possible relationship between SII and anemia. Methods: This retrospective cross-sectional survey was conducted using data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) population. In total, 19851 American adults aged ≥18 years were included. SII was calculated as the platelet count×neutrophil count/lymphocyte count. Anemia was defined as hemoglobin (Hgb) levels of < 13 g/dL in males and < 12 g/dL in females. Logistic regression analyses, subgroup analyses and sensitivity analyses were performed to investigate the relationship between SII and anemia. Results: Our study included a total of 19851 patients, of which 1501 (7.6%) had anemia. After adjusting for all covariates, the multivariate logistic regression analysis showed that a higher SII (In-transform) level was associated with increased likelihood of anemia (OR=1.51, 95% CI: 1.36-1.68, P<0.001). The association between SII and anemia exhibited a nonlinear manner. The positive correlation between SII and anemia was related to the severity of anemia. Subgroup analysis showed that there was no significant dependence on age, family income, body mass index, hypertension, kidney disease and cancer except gender on this positive association. Furthermore, sensitivity analyses confirmed the robustness of our results. Conclusion: Our study demonstrated that SII was positively associated with anemia especially among female participants. And this positive correlation was related to the severity of anemia. Further large-scale prospective studies are still needed to analyze the role of SII in anemia.

Tumor-associated CD8+T cell tolerance induced by erythroid progenitor cells.

Introduction: CD8+T cell tolerance plays an important role in tumor escape. Recent studies have shown that CD45+ erythroid progenitor cells (CD45+EPCs) generated through splenic extramedullary erythropoiesis suppress tumor immunity. However, the mechanism underlying how CD45+EPCs mediate CD8+T cell tolerance remains incompletely understood and requires further research. Methods: In this study, the antigen-processing abilities of CD45+EPCs was verified through both in vitro and in vivo experiments. We have used the method of co-culture in vitro and adoptive transfer experiments in vivo to explore the effects of CD45+EPCs on CD8+T cell tolerance. RNA-sequencing analysis and blocking experiments were used to evaluate the role of ROS in the CD45+EPC mediated tolerance of CD8+T cells. Finally, we incorporated uric acid into the adoptive transfer experiments to rescue the CD45+EPC mediated tumor-promoting effect. Results and discussion: We found that CD45+EPCs take up soluble proteins, present antigenic epitopes on their surface, and induce antigen-specific CD8+T cell anergy. In addition, we found that CD45+EPC directly nitrates tyrosine within the TCR/CD8 complex via the production of reactive oxygen species and peroxynitrite, preventing CD8+ T cells from responding to their specific peptide antigens. Furthermore, uric acid treatment effectively abolished the immunosuppressive effects of CD45+EPCs during CD8+T cell adoptive transfer, thereby enhancing the anti-tumor efficacy. These results demonstrated that CD8+T cell tolerance in tumor-bearing mice is induced by CD45+EPCs. The results of this study have direct implications for tumor immunotherapy.