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Haopeng Wang,1,* Hua Zhao,1,* Zheng Chen,1,* Xiaomin Cai,1 Xuhui Wang,1 Ping Zhou,1 Yinda Tang,1 Tingting Ying,1 Xin Zhang,1 Yiman Shen,1 Baimiao Wang,1 Wanchun Zhu,1 Jin Zhu,1 Xinjun Wang,2 Shiting Li1 1Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shiting Li, Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, People’s Republic of China, Email lishiting@xinhuamed.com.cn Xinjun Wang, Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Email wangxj@zzu.edu.cnBackground: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism.Methods: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments.Results: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p.Conclusion: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI. Keywords: hypoxic, BMSCs, exosomes, Schwann cells, facial nerve injury

The present work aims to research the treatment processing of magnesium reinforced with 1 μmsilicon carbide particle (SiCp) using stir casting combined by ultrasonic vibration. Present studies have been done on six different materials: (a) AZ31B alloy without particles, (b) 5 vol.% SiCp/AZ31B composites fabricated with different semi-solid stirring time (5 min, 10 min, 15 min and 20 min), (c) composite with 20 vol.% SiCp. The effects of 1 μm/SiCp pretreatment and stirring time on microstructure and interfacial wettability as well as mechanical properties of the materials were confirmed. Both short and long stirring time for the particle dispersion brought particle agglomeration. Results of SEM microstructure and tensile properties exhibited that the optimal stirring parameters of 625 °C/1500 rpm/15 min are exploited, and 20 vol.% SiCp/AZ31B composite was fabricated by the optimal stirring parameters. The application of optimal stirring parameters for the treatment resulted in homogeneous particle distribution. The addition of SiCp leads to a reduced matrix grain, and 20 vol.% SiCp/AZ31B composite showed smaller grain size than. 5 vol.% SiCp/AZ31B composite. The interface between SiCp and matrix is clear and interfacial wettability well. Tensile test results show that with increasing SiCp content, strengths increase while ductility decreases.

Pneumatic muscle actuators are newly developed actuators in rotational, non-aligned and specified applications. In this paper, pneumatic muscle actuators are used to set up a two-dimensional pneumatic arm to simulate the excavator's motion. Fuzzy control algorithms are typically applied in pneumatic control systems owing to their non-linearity and ill-defined mathematical models. Two fuzzy controllers, which include the sliding mode fuzzy controller and self-organizing fuzzy controller, are comparatively implemented in this 2D pneumatic arm control system. The present paper provides the comparisons of trajectory tracking performances and adaptations of these two fuzzy controllers via a variety of trajectory tracking experiments.

The 44-item Big Five Personality Inventory (BFI-44) helps in simplify a wide range of complex personality features, including how personality affects breastfeeding. The aim of this study was to examine the reliability of the Malay version of the BFI-44. A cross-sectional study was conducted using the convenience sampling of female respondents. A total of 96 female public university students participated in this study. Cronbach's alpha, intraclass correlation coefficient, limit of agreement, and standard error of measurement (SEM) were used in determining the reliability of the questionnaire. Cronbach's alpha value for Extraversion subscale obtained the highest internal consistency (0.723) and the lowest internal consistency was obtained in the subscale of Openness to Experience (0.543). The intraclass correlation coefficient (ICC) value for all dimensions exceeded 0.70 (ICC= 0.792- 0.883). The Bland-Altman plots showed high reliability in all dimensions except Neuroticism. For SEM, Extraversion scored the lowest (0.773) while Neuroticism scored the highest (1.199). Overall, the BFI-44 in Malay version had moderate to good internal consistency and high test-retest reliability. These findings may give positive implications for the implementation of the questionnaire in future evaluation of Malaysians' personality traits. [ABSTRACT FROM AUTHOR]

Background: Acting as mediators in cell-matrix and cell-cell communication, matricellular proteins play a crucial role in cancer progression. Thrombospondins (TSPs), a type of matricellular glycoproteins, are key regulators in cancer biology with multifaceted roles. Although TSPs have been implicated in anti-tumor immunity and epithelial-mesenchymal transition (EMT) in several malignancies, their specific roles to colon cancer remain elusive. Addressing this knowledge gap is essential, as understanding the function of TSPs in colon cancer could identify new therapeutic targets and prognostic markers. Methods: Analyzing 1981 samples from 10 high-throughput datasets, including six bulk RNA-seq, three scRNA-seq, and one spatial transcriptome dataset, our study investigated the prognostic relevance, risk stratification value, immune heterogeneity, and cellular origin of TSPs, as well as their influence on cancer-associated fibroblasts (CAFs). Utilizing survival analysis, unsupervised clustering, and functional enrichment, along with multiple correlation analyses of the tumor-microenvironment (TME) via Gene Set Variation Analysis (GSVA), spatial localization, Monocle2, and CellPhoneDB, we provided insights into the clinical and cellular implications of TSPs. Results: First, we observed significant upregulation of THBS2 and COMP in colon cancer, both of which displayed significant prognostic value. Additionally, we detected a significant positive correlation between TSPs and immune cells, as well as marker genes of EMT. Second, based on TSPs expression, patients were divided into two clusters with distinct prognoses: the high TSPs expression group (TSPs-H) was characterized by pronounced immune and stromal cell infiltration, and notably elevated T-cell exhaustion scores. Subsequently, we found that THBS2 and COMP may be associated with the differentiation of CAFs into pan-iCAFs and pan-dCAFs, which are known for their heightened matrix remodeling activities. Moreover, THBS2 enhanced CAFs communication with vascular endothelial cells and monocyte-macrophages. CAFs expressing THBS2 (THBS2+ CAFs) demonstrated higher scores across multiple signaling pathways, including angiogenic, EMT, Hedgehog, Notch, Wnt, and TGF-β, when compared to THBS2- CAFs. These observations suggest that THBS2 may be associated with stronger pro-carcinogenic activity in CAFs. Conclusions: This study revealed the crucial role of TSPs and the significant correlation between THBS2 and CAFs interactions in colon cancer progression, providing valuable insights for targeting TSPs to mitigate cancer progression.

Abstract From social and economic perspectives, compositional data represent the proportions of various components within a whole, carrying non-negative values and providing only relative information. However, in many circumstances, there are often a significant number of missing values in datasets. Due to the complexity caused by these missing values, traditional estimation methods are ineffective. In this paper, an adaptive group LASSO-based imputation method is proposed for compositional data, consolidating the advantages of group LASSO and adaptive LASSO analysis techniques. Considering the impact of outliers on the accuracy of estimation, both simulation and case analysis are conducted to compare the proposed algorithm against four existing methods. The experimental results demonstrate that the proposed adaptive group LASSO method produces a better imputation performance at comparable missing rates.

Abstract Background Lung adenocarcinoma (LUAD) is one of the most common malignant tumors. Although several treatments have been proposed, the long-term prognosis of this cancer is poor. Lipid droplets and mitochondria are important organelles that regulate energy metabolism in cells and are postulated to promote the occurrence and progression of tumors. However, few risk prediction models have been constructed based on lipid drop-mitochondria-related genes (LMRGs). Methods In this study, we constructed a lipid drop-mitochondrial (LD-M) risk score model based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Biological functions and clinical benefits associated with the various risk scores were analyzed using R software, GraphPad Prism 9, and the online database system. Results An LD-M risk score model comprising ABLIM3, AK4, CAV2, CPS1, CYP24A1, DLGAP5, FGR, and SH3BP5, was developed and its predictive power was validated. The risk score was closely associated with the cell cycle. Immunophenoscore (IPS) and Tumor immune dysfunction and exclusion (TIDE) results demonstrated that the low-risk group was more sensitive to immunotherapy. Drug sensitivity analysis indicated that BMS-754807, ZM447439, SB216763, and other drugs had lower IC50 values in the low-risk group. Conclusion Our results suggest that the LD-M risk score is an effective prognostic indicator for individualized treatment of LUAD.

Abstract Background Uveal melanoma (UM) is a rare and deadly eye cancer with high metastatic potential. Despite the predominance of malignant cells within the tumor microenvironment, the heterogeneity and underlying molecular features remain to be fully characterized. Methods We analyzed single-cell transcriptomic profiling of 37,660 malignant cells from 17 UM tumors. A consensus non-negative factorization algorithm was used to decipher transcriptional programs underlying tumor cell-intrinsic heterogeneity. Tumor-infiltrated immune cells were computationally estimated from bulk transcriptomes and bioinformatics methods. A gene signature was derived for subtyping and prognostic stratification and validated in multicenter cohorts. Results ScRNA-seq analysis revealed the existence of diverse subpopulations and transcriptional variability among malignant cells within and between tumors. Furthermore, we observed that the heterogeneity of malignant cell states and compositions correlated with genomic, immunological, and clinical characteristics. By identifying gene expression programs associated with malignant cell heterogeneity at the single cell level, UM samples were classified into two distinct intra-tumoral subtypes (ITMHlo and ITMHhi) with different prognoses and immune microenvironments. Finally, a machine learning-derived 9-gene signature was developed to translate single-cell information into bulk tissue transcriptomes for patient stratification and was validated in multicenter cohorts. Conclusions Our study provides insight into understanding the intra-tumoral heterogeneity of UM and its potential impact on patient stratification.

C-myc is a proto-oncogene that plays an important role in a variety of diseases. There were a lot of research on the correlation between C-myc and human viruses. However, the study about C-myc related to aquatic species virus is very limited. In the present study, the qRT-PCR, cellular immunofluorescence and western blotting determination data reported that C-myc and glutaminase (GLS) genes were significantly upregulated when grouper fin cells (GF-1) were infected with red grouper nervous necrosis virus (RGNNV). After knocking down the C-myc gene, the mRNA and protein levels of GLS, capsid protein (CP) and RNA polymerase (RdRp) of RGNNV were significantly reduced in RGNNV-infected GF-1 cells and the overexpression of the C-myc gene remarkably promoted these genes, which indicated that the replication of the virus and GLS gene were positively regulated by C-myc in RGNNV-infected GF-1 cells. In addition, supplementation of exogenous ATP can partially restore viral replication when RGNNV-infected GF-1 cells were cultured in glutamine-free medium, which confirmed that the glutamine was decomposed into ATP to provide energy for viral replication. Further studies confirmed that overexpression of C-myc can increase the content of ATP in normal cells. To sum up, these data suggested that activation of C-myc gene affected viral replication by regulating GLS expression to drive glutamine dissolution.

Periodontitis is an inflammatory disease caused by bacterial biofilms, which leads to the destruction of periodontal tissue. Current treatments, such as mechanical cleaning and antibiotics, struggle to effectively address the persistent biofilms, inflammation, and tissue damage. A new approach involves developing a Janus nanomotor (J-CeM@Au) by coating cerium dioxide-doped mesoporous silica (CeM) with gold nanoparticles (AuNPs). This nanomotor exhibits thermophoretic motion when exposed to near-infrared (NIR) laser light due to the temperature gradient produced by the photothermal effects of asymmetrically distributed AuNPs. The NIR laser provides the energy for propulsion and activates the nanomotor's antibacterial properties, allowing it to penetrate biofilms and kill bacteria. Additionally, the nanomotor's ability to scavenge reactive oxygen species (ROS) can modulate the immune response and create a regenerative environment, promoting the healing of periodontal tissue. Overall, this multifunctional nanomotor offers a promising new approach for treating periodontitis by simultaneously addressing biofilm management and immune modulation with autonomous movement.

Abstract Background Balance dysfunction affects 70% of stroke patients. Emerging neurophysiological approaches, such as virtual reality therapy (VRT) and repetitive transcranial magnetic stimulation (rTMS), have been proven by clinical studies that the balance function of stroke patients can be improved when applied alone, but there are relatively few studies on the combined treatment of balance dysfunction after stroke. This study aimed to evaluate the impact of a 4-week intensive intervention combining VRT and rTMS on both balance function and brain plasticity among stroke patients. Methods This single-blind, randomized controlled trial was conducted at the Rehabilitation Medical Center of the Rehabilitation General Hospital of Ningxia Medical University. A cohort of 136 stroke patients, with durations of 2 to 24 weeks post-stroke, were enrolled in the study. Participants were randomly allocated in a 1:1:1:1 ratio to four groups: the VR group (n = 34), the rTMS group (n = 34), the combined treatment group receiving both VR and rTMS (n = 34), and the control group undergoing traditional balance training (n = 34). All patients underwent a standardized inpatient rehabilitation program over 4 weeks. The VR group received daily 30-min sessions of VR therapy for 20 days. The rTMS group underwent daily sessions of rTMS stimulation for 20 min, targeting the motor imagery region in the affected hemisphere. The combination group received VR therapy after completing their rTMS treatment. The control group received conventional balance training, with each session lasting 30 min. Additionally, all patients received an extra 60 min of standard rehabilitation therapy twice daily. Assessments were conducted at baseline, 2 weeks, and 4 weeks post-treatment, using the Berg Balance Scale (BBS) as the primary measure, and secondary measures including the Timed Up-and-Go Test (TUGT), Fugl-Meyer Assessment-Lower Extremity (FMA-LE), and 6-m walking test (6MWT), as well as assessments for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VGEF), tyrosine receptor kinase (TrκB), motor-evoked potential latency (PL), central motor conduction time (CMCT), and amplitude. Discussion The widespread application of VR technology and rTMS in clinical settings is well-established. However, the potential synergistic effects of combining these modalities on balance function and neuroplasticity in stroke patients remain uncertain. Our hypothesis suggests that the integration of VR with rTMS may result in more pronounced improvements in both balance function and neuroplasticity among stroke patients, surpassing the outcomes achievable with VR alone, rTMS alone, or traditional therapy. The possible mechanism is that VR-based training combined with rTMS plays a superimposed effect, promoting better repair of damaged neurons and ultimately improving balance function in stroke patients. The positive results anticipated from this trial could provide objective evidence advocating for the concurrent use of VR and rTMS in clinical interventions. Trial registration The study protocol underwent review and approval by the Medical Research Ethics Committee of the General Hospital of Ningxia Medical University on January 26, 2024 (No. KYLL-2024–0162). Subsequently, it was registered in the Chinese Clinical Trial Registry on March 11, 2024 (registration number: ChiCTR2400081775). Currently, the study is still ongoing.

Abstract Vector beams have attracted widespread attention because of their unique optical properties; in particular, their combination with tight focusing can produce many interesting phenomena. The rise of 3D printing technology provides more possibilities for exploration. In this work, a cascading method involving a metamaterial and a metalens is used to generate a tightly focused field of vector beams in the terahertz band, which is prepared via 3D printing. As a proof-of-concept demonstration, a series of metamaterial modules capable of generating states of different orbital angular momentum are proposed by cascading with a metalens. The experimental results are in good agreement with the simulation results, fully verifying the feasibility of the scheme. The proposed design and fabrication strategy provides a new idea for the tight focusing of terahertz vector beams.

Abstract Background Knee osteoarthritis (KOA) was characterized by pain and limited joint function, which seriously affected the quality of life of patients. The vast majority of KOA was closely related to degeneration of the patellofemoral joint and abnormal patellar movement trajectory. Tissue-bone homeostasis manipulation (TBHM) could correct abnormal patellar movement trajectory on the basis of loosening soft tissue. However, there was little strong evidence to verify its efficacy on the patients with KOA. The study objective was to explore the efficacy of the TBHM on gait and knee function in the patients with KOA. Methods Sixty KOA patients were randomly assigned to either the joint mobilization (n = 30) or TBHM (n = 30) group. The joint mobilization group received joint mobilization, while the TBHM group received TBHM. For two groups, the patients participated in 30 min rehabilitation sessions thrice per week for 12 weeks. The primary outcome was biomechanical gait outcomes during walking, including step length, step velocity, double support, knee range of motion (ROM), and knee adduction moment (KAM). The secondary outcomes were the Western Ontario and McMaster Index (WOMAC) and 36-Item short- form health survey (SF-36), which reflected improvements in knee function and quality of life, respectively. At baseline and 12 weeks, evaluations were conducted and compared between groups. Results After a 12-week intervention, significant group differences were observed in KAM (p = 0.018), WOMAC-Pain (p = 0.043) and WOMAC-Stiffness (p = 0.026). A noteworthy finding was the presence of a significant interaction effect between group and time specifically observed in step velocity during gait (p = 0.046), WOMAC-Function (p = 0.013) and SF-36 (p = 0.027). Further analysis revealed a significant difference in step velocity (p = 0.034), WOMAC-Function (p = 0.025) and SF-36 (p = 0.042) during post-assessment between the two groups. Moreover, a significant time effect was observed across all outcomes of the two groups (p

Abstract Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth and durability, it is desirable to deliver both the viral hemagglutinin and neuraminidase glycoproteins. Delivering multiple antigens individually, however, complicates manufacturing and increases cost, thus it would be beneficial to express both proteins from a single mRNA. Here, we develop an mRNA genetic configuration that allows the simultaneous expression of unmodified, full-length NA and HA proteins from a single open reading frame. We apply this approach to glycoproteins from contemporary influenza A and B viruses and, after vaccination, observe high levels of functional antibodies and protection from disease in female mouse and male ferret challenge models. This approach may further efforts to utilize mRNA technology to improve seasonal vaccine efficacy by efficiently delivering multiple viral antigens simultaneously and in their native state.

Dielectric ceramics with low permittivity (εr), high quality factor (Q×f), and near-zero resonant frequency (τf) in the microwave bands are key materials used in fifth/sixth-generation (5G/6G) telecommunication, whileτf of most low-εr microwave dielectric ceramics is relatively negative. In this work, the first low-εr Ga-based ceramic SrGa12O19 with an anomalous positive τf was reported, and the causes of the positive τf, intrinsic polarization, and loss mechanism were systematically studied. X-ray diffraction (XRD) and transmission electron microscopy (TEM) revealed that the SrGa12O19 ceramic formed a pure hexagonal magnetoplumbite structure with spinel blocks and rock-salt blocks stacked along the crystallographic c-axis. When sintered at 1430 °C, it possessed the optimal microwave dielectric properties of a low εr of 14.46, high Q×f of 64,705 GHz, and exceptional positive τf of +55.7 ppm/°C, along with a low linear thermal expansion coefficient (αL) of 11.617 ppm/°C. The large positive deviation between εr and εr(C–M) of 45.31% resulted from the rattling effect of atoms in the rock-salt block. The unique positive τf (+55.7 ppm/°C) was governed by the rattling effect, resulting in a positive ταm (the temperature coefficient of ion polarizability) of 8.489 ppm/°C and a large negative temperature coefficient of permittivity (τε) of −132.864 ppm/°C. Phillips–Vechten–Levine (P–V–L) chemical bond theory revealed greater contributions of the spinel block to bond ionicity (fi, 52.95%), permittivity (ε, 55.15%), bond energy (E, 56.87%), and lattice energy (U, 74.88%) than those of the rock-salt block. The intrinsic dielectric properties were analyzed using infrared (IR) reflectivity spectra. The favorable performance of the SrGa12O19 ceramic indicated that it is a novel τf compensator. This selection of compounds with different structural layer combinations provides a new idea for exploring excellent microwave dielectric ceramics.

Abstract Background Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforward technique for identifying the pathogenic agent in clinical specimens is crucial to reduce fatality rates and facilitate timely antimicrobial treatment. In this study, we aimed to identify Nocardia spp. in clinical isolates, using MALDI-TOF MS as the primary method, with molecular methods as the gold standard. Clinical Nocardia isolates were identified using 16S rRNA/hsp65/gyrB/secA1/rpoB gene sequencing. Identification performance of the Bruker MALDI Biotyper 3.1 (V09.0.0.0_8468) and MBT Compass 4.1 (V11.0.0.0_10833) for Nocardia identification was evaluated. Results Seventy-six Nocardia isolates were classified into 12 species through gene sequencing. The MALDI Biotyper 3.1 (V09.0.0.0_8468) achieved 100% genus-level accuracy and 84.2% species accuracy (64/76). The MBT Compass 4.1 with the BDAL Database (V11.0.0.0_10833) improved species identification to 98.7% (75/76). The updated database enhanced species level identification with scores > 1.7, increasing from 77.6% (59/76) to 94.7% (72/76), a significant improvement (P = 0.001). The new and simplified extraction increased the proportion of strains identified to the species level with scores > 1.7 from 62.0% (18/29) to 86.2% (25/29) (P = 0.016). An in-house library construction ensured accurate species identification for all isolates. Conclusions The Bruker mass spectrometer can accurately identify Nocardia species, albeit with some variations observed between different database versions. The MALDI Biotyper 3.1 (V09.0.0.0_8468) has limitations in identifying Nocardia brasiliensis, with some strains only identifiable to the genus level. MBT Compass 4.1 (V11.0.0.0_10833) effectively addresses this shortfall, improving species identification accuracy to 98.7%, and offering quick and reliable identification of Nocardia. Both database versions incorrectly identified the clinically less common Nocardia sputorum as Nocardia araoensis. For laboratories that have not upgraded their databases and are unable to achieve satisfactory identification results for Nocardia, employing the new and simplified extraction method can provide a degree of improvement in identification outcomes.

Abstract Purpose This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients. Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis. Results This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p

Abstract In food circular economy, the utilization of food manufacturing side streams (FMSS) offers significant potential instead of being discarded. However, reincorporating FMSS into the food value chain raises food safety concerns due to potential food hazards. This perspective explores food safety risks associated with circular management of FMSS by using a ‘Quad-Modal hazard dynamic’ approach with case studies. Future research and advancements in food safety control strategies are also discussed.

Abstract Cognitive dysfunction caused by diabetes has become a serious global medical issue. Diabetic kidney disease (DKD) exacerbates cognitive dysfunction in patients, although the precise mechanism behind this remains unclear. Here, we conducted an investigation using RNA sequencing data from the Gene Expression Omnibus (GEO) database. We analyzed the differentially expressed genes in DKD and three types of neurons in the temporal cortex (TC) of diabetic patients with cognitive dysfunction. Through our analysis, we identified a total of 133 differentially expressed genes (DEGs) shared between DKD and TC neurons (62 up-regulated and 71 down-regulated). To identify potential common biomarkers, we employed machine learning algorithms (LASSO and SVM-RFE) and Venn diagram analysis. Ultimately, we identified 8 overlapping marker genes (ZNF564, VPS11, YPEL4, VWA5B1, A2ML1, KRT6A, SEC14L1P1, SH3RF1) as potential biomarkers, which exhibited high sensitivity and specificity in ROC curve analysis. Functional analysis using Gene Ontology (GO) revealed that these genes were primarily enriched in autophagy, ubiquitin/ubiquitin-like protein ligase activity, MAP-kinase scaffold activity, and syntaxin binding. Further enrichment analysis using Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) indicates that these biomarkers may play a crucial role in the development of cognitive dysfunction and diabetic nephropathy. Building upon these biomarkers, we developed a diagnostic model with a reliable predictive ability for DKD complicated by cognitive dysfunction. To validate the 8 biomarkers, we conducted RT-PCR analysis in the cortex, hippocampus and kidney of animal models. The results demonstrated the up-regulation of SH3RF1 in the cortex, hippocampus and kidney of mice, which was further confirmed by immunofluorescence and Western blot validation. Notably, SH3RF1 is a scaffold protein involved in cell survival in the JNK signaling pathway. Based on these findings, we support that SH3RF1 may be a common gene expression feature that influences DKD and cognitive dysfunction through the apoptotic pathway.

Abstract Background To investigate the anatomic features of the root furcation of permanent mandibular first molars. Methods A total of 50 extracted mandibular first molars (25 two-rooted and 25 three-rooted) were collected and scanned using micro-computed tomography. The digital models of teeth and root canal systems were reconstructed three-dimensionally. The tooth models were displayed in parallel projection mode from buccal and distal views. Screenshots were captured and subsequently analyzed using Image-Pro Plus 6.0 software after calibration. The furcation angle, root trunk length, maximum depth and level of distal root concaves of mesial roots, and length of enamel projections were measured, and the furcation types (classified into type V, type U and type W) were detected. Statistical analysis was performed using the Shapiro-Wilk’s test, one-way analysis of variance, Student’s t-test and Chi-square test. Results The mean furcation angle between the distobuccal (DB) and distolingual (DL) roots (in distal view) was the greatest (59.2°), whereas the furcation angle between the mesial and DL roots (in buccal view) was the smallest (25.4°) among the four furcation angles (all p 0.05). The frequency of type V was the highest (54.0%), followed by type U (26.0%), and type W had the lowest occurrence rate (20.0%). The mean length of distal root trunk in the three-rooted mandibular molars was significantly greater than that of the buccal/lingual one (3.7 mm vs. 3.0 mm, p

Abstract Background Long-term accumulation of misfolded proteins leads to endoplasmic reticulum (ER) stress in colorectal cancer (CRC). However, the precise pathways controlling the decision between survival and apoptosis in CRC are unclear. Therefore, in this study, we investigated the function and molecular mechanism of glucosidase I (GCS1) in regulating ER stress in CRC. Methods A public database was used to confirm the expression level of GCS1 in CRC and normal tissues. Clinical samples from our center were used to confirm the mRNA and protein expression levels of GCS1. Cell proliferation, migration, invasion, and apoptosis assays revealed the biological role of GCS1. Immunohistochemical techniques were used to evaluate the expression of key proteins in subcutaneous implanted tumors in nude mice, which provided further evidence for the biological function of GCS1 in promoting cancer in vivo. The results of coimmunoprecipitation-mass spectrometry analysis and immunofluorescence colocalization analysis the interaction between GCS1 and GRP78. In addition, the mechanism of action of USP10, GRP78, and GCS1 at the post- translational level was investigated. Finally, a tissue microarray was used to examine the connection between GCS1 and GRP78 expression and intracellular localization of these proteins using immunohistochemistry and immunofluorescence. Results The experimental results revealed that GCS1 was substantially expressed in CRC, with higher expression indicating a worse prognosis. Thus, GCS1 can enhance the proliferation and metastasis while inhibiting the apoptosis of CRC cells both in vivo and in vitro. Mechanistically, GCS1 binds to GRP78, recruits USP10 for deubiquitination of GRP78 to promote its degradation, and decreases ER stress-mediated apoptosis, increasing CRC cell proliferation and metastasis. Conclusions In summary, GCS1 stimulates CRC growth and migration and reduces ER stress-mediated apoptosis via USP10-mediated deubiquitination of GRP78. Our findings identify a possible therapeutic target for CRC.

Abstract There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop new systems for treating bone related diseases and even repurposing current drug therapies. In this review, we shall summarise the latest progress in this area and present a perspective for future development in the field. We will focus on calcium-based nanoparticle systems that modulate calcium metabolism and consequently, the bone microenvironment to inhibit disease progression (including cancer). We shall also review the bone affinity drug family, bisphosphonates, as both a nano-drug and nano-delivery system for bone targeted therapy. The ability to target and release the drug in a controlled manner at the disease site represents a promising safe therapy to treat bone diseases in the future.

Heart rate variability (HRV) is an important metric in cardiovascular health monitoring. Spectral analysis of HRV provides essential insights into the functioning of the cardiac autonomic nervous system. However, data artefacts could degrade signal quality, potentially leading to unreliable assessments of cardiac activities. In this study, we introduced a novel approach for estimating uncertainties in HRV spectrum based on matrix completion. The proposed method utilises the low-rank characteristic of HRV spectrum matrix to efficiently estimate data uncertainties. In addition, we developed a refined matrix completion technique to enhance the estimation accuracy and computational cost. Benchmarking on five public datasets, our model shows effectiveness and reliability in estimating uncertainties in HRV spectrum, and has superior performance against five deep learning models. The results underscore the potential of our developed matrix completion-based statistical machine learning model in providing reliable HRV spectrum uncertainty estimation.

Based on the principle of super-symmetric lens with quadratic phase gradient transformation, combined with the principle of digital coding of metasurface, we propose a wide-angle coded metalens for focusing control in two-dimensional space. This metalens achieves focus shift in the x-direction by changing the oblique incidence angle of the incident wave, and focus control in the y-direction by combining with the convolution principle of the digitally coded metasurface to achieve flexible control of light focusing in the two-dimensional plane. The metasurface unit is mainly composed of three-layer of metal structure and two layers of medium, and the transmission phase is obtained by changing the middle layer of metal structure, which in turn obtains the required phase distribution of the metalens. The design of the metalens realizes the function of the lens with a large viewing angle at the x-polarized incidence, and realizes two-dimensional focus control. Experimentally, we prepared the designed coding metalens and tested the focus control function of the wide-angle coding metalens. The experimental results are in good agreement with the design results.

Abstract Background Rhodococcus equi (R. equi) is a Gram-positive zoonotic pathogen that frequently leads to illness and death in young horses (foals). This study presents the complete genome sequence of R. equi strain BJ13, which was isolated from a thoroughbred racehorse breeding farm in Beijing, China. Results The BJ13 genome has a length of 5.30 Mb and consists of a complete chromosome and a plasmid measuring 5.22 Mb and 0.08 Mb, respectively. We predicted 4,929 coding gene open reading frames, along with 52 tRNAs and 12 rRNAs. Through analysis of mobile genetic elements, we identified 6 gene islands and 1 prophage gene. Pathogenic system analysis predicted the presence of 418 virulence factors and 225 drug resistance genes. Secretion system analysis revealed the prediction of 297 secreted proteins and 1,106 transmembrane proteins. BJ13 exhibits genomic features, virulence-associated genes, potential drug resistance, and a virulence plasmid structure that may contribute to the evolution of its pathogenicity. Lastly, the pathogenicity of the isolated strain was assessed through animal experiments, which resulted in inflammatory reactions or damage in the lungs, liver, and spleen of mice. Moreover, by the 7th day post-infection, the mortality rate of the mice reached 50.0%, indicating complex immune regulatory mechanisms, including overexpression of IL-10 and increased production of pro-inflammatory cytokines like TNF-α. These findings validate the strong pathogenicity of the isolated strain and provide insights for studying the pathogenic mechanisms of Rhodococcus equi infection. Conclusions The complete genome sequence of R. equi strain BJ13 provides valuable insights into its genomic characteristics, virulence potential, drug resistance, and secretion systems. The strong pathogenicity observed in animal experiments underscores the need for further investigation into the pathogenic mechanisms of R. equi infection.

Abstract Noise is usually regarded as adversarial to extracting effective dynamics from time series, such that conventional approaches usually aim at learning dynamics by mitigating the noisy effect. However, noise can have a functional role in driving transitions between stable states underlying many stochastic dynamics. We find that leveraging a machine learning model, reservoir computing, can learn noise-induced transitions. We propose a concise training protocol with a focus on a pivotal hyperparameter controlling the time scale. The approach is widely applicable, including a bistable system with white noise or colored noise, where it generates accurate statistics of transition time for white noise and specific transition time for colored noise. Instead, the conventional approaches such as SINDy and the recurrent neural network do not faithfully capture stochastic transitions even for the case of white noise. The present approach is also aware of asymmetry of the bistable potential, rotational dynamics caused by non-detailed balance, and transitions in multi-stable systems. For the experimental data of protein folding, it learns statistics of transition time between folded states, enabling us to characterize transition dynamics from a small dataset. The results portend the exploration of extending the prevailing approaches in learning dynamics from noisy time series.

Abstract Background Fungal toxins are highly toxic and widely distributed, presenting a considerable threat to global agricultural development. Addressing the issue of aflatoxin B1 (AFB1) contamination in feed, it is crucial to ascertain the effectiveness and mechanisms of microbial strains in degradation. Results This study used isotope tracing and nuclear magnetic resonance (NMR) to investigate the degradation products of Bacillus amyloliquefaciens YUAD7 in complex substrates. By tracing 14C34-AFB1 and utilizing NMR, ultra-performance liquid chromatography–quadrupole time-of-flight/mass spectrometry (UPLC–Q-TOF/MS) purification and identification techniques, it was confirmed that AFB1 was degraded by YUAD7 into C12H14O4, C5H12N2O2, C10H14O2, and C4H12N2O, effectively removing 99.7% of AFB1 (100 μg/kg) from alfalfa silage. YUAD7 targeted the ester bond in the vanillin lactone ring structure, the ether bond in the furan ring structure, and the unsaturated carbon–carbon double bond in the furan ring structure during AFB1 degradation, disrupting the toxic sites responsible for AFB1's carcinogenic, teratogenic, and mutagenic effects and achieving biodegradation. Moreover, B. amyloliquefaciens YUAD7 transformed AFB1 through processes like hydrogenation, enzyme modification, and the loss of the -CO group while also being associated with metabolic pathways such as alanine, aspartate, glutamate metabolism, glutathione metabolism, cysteine and methionine metabolism, and pentose and glucuronate interconversions. Conclusions The utilization of isotope tracing allowed for rapid identification of degradation products in complex substrates, while NMR elucidated the structures of these products. This deepens our understanding of AFB1 biodegradation mechanisms, providing technical support for the practical application of these bacteria in degradation, and new insights into studying the biological degradation mechanism. B. amyloliquefaciens YUAD7 can be used as a potential strain for degrading AFB1 in large-scale silage. Graphical Abstract

Abstract Background Visceral fat accumulation and obesity-induced chronic inflammation have been proposed as early markers for multiple disease states, especially in women. Nevertheless, the potential impact of fat distribution on α1-acid glycoprotein(AGP), a marker of inflammation, remains unclear. This research was conducted to investigate the relationships among obesity, fat distribution, and AGP levels. Methods A cross-sectional observational study was performed using blood samples from adult females recruited through the National Health and Nutrition Examination Survey from 2015 to 2018. Serum levels of AGP were measured using the Tina-quant α-1-Acid Glycoprotein Gen.2 assay. Based on the fat distribution data obtained from dual-energy X-ray absorptiometry assessments, body mass index (BMI), total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android fat/gynoid fat ratio (AGR), visceral percent fat (VPF), subcutaneous percent fat (SPF), visceral fat/subcutaneous fat ratio (VSR) were used as dependent variables. To investigate the link between fat distribution and AGP, multivariate linear regression analysis was utilized. Furthermore, a sensitivity analysis was also performed. Results The present study included 2,295 participants. After adjusting for covariates, BMI, TPF, APF, GPF, VPF, and SPF were found to be positively correlated with AGP levels (BMI: β = 23.65 95%CI:20.90–26.40; TPF: β = 25.91 95%CI:23.02–28.80; APF: β = 25.21 95%CI:22.49–27.93; GPF: β = 19.65 95%CI:16.96–22.34; VPF: β = 12.49 95%CI:9.08–15.90; SPF: β = 5.69, 95%CI:2.89–8.49; AGR: β = 21.14 95%CI:18.16–24.12; VSR: β = 9.35 95%CI:6.11–12.59, all P

Abstract Hyperproliferation of vascular smooth muscle cells (VSMCs) is a driver of hypertensive vascular remodeling. This study aimed to uncover the mechanism of BTB and CNC homology 1 (BACH1) and microRNAs (miRNAs) in VSMC growth and hypertensive vascular remodeling. With the help of TargetScan, miRWalk, miRDB, and miRTarBase online database, we identified that BACH1 might be targeted by miR-196a-5p, and overexpressed in VSMCs and aortic tissues from spontaneously hypertensive rats (SHRs). Gain- and loss-of-function experiments demonstrated that miR-196a-5p suppressed VSMC proliferation, oxidative stress and hypertensive vascular remodeling. Double luciferase reporter gene assay and functional verification showed that miR-196a-5p cracked down the transcription and translation of BACH1 in both Wistar Kyoto rats (WKYs) and SHRs. Silencing BACH1 mimicked the actions of miR-196a-5p overexpression on attenuating the proliferation and oxidative damage of VSMCs derived from SHRs. Importantly, miR-196a-5p overexpression and BACH1 knockdown cooperatively inhibited VSMC proliferation and oxidative stress in SHRs. Furthermore, miR-196a-5p, if knocked down in SHRs, aggravated hypertension, upregulated BACH1 and promoted VSMC proliferation, all contributing to vascular remodeling. Taken together, targeting miR-196a-5p to downregulate BACH1 may be a promising strategy for retarding VSMC proliferation and hypertensive vascular remodeling.

Abstract Background Methylenetetrahydrofolate reductase (MTHFR) is essential for the metabolism of folic acid and homocysteine. The MTHFR C677T polymorphism is associated with several disorders. Our study aims to explore the geographical distributions of the MTHFR C677T polymorphism of women in China and how migration affected the polymorphism in Suzhou. Methods A total of 7188 women of reproductive age were recruited in Suzhou of the study. Subjects were classified according to their native places after data extraction. MTHFR C677T gene polymorphisms were detected by quantitative PCR with genomic DNA isolated from blood samples. Results The frequencies of the 677T allele and 677TT genotype were higher in northern China than that in southern China and decreased in geographical gradients from north to south. The frequencies were considerably higher in the migrant population than that in the indigenous population of Suzhou. The migrant population have gradually changed the prevalence in Suzhou. Conclusions Our study suggested that the prevalence of MTHFR C677T polymorphisms among women varied across different geographical regions in Chinese Han populations. The 677T allele frequencies of the northern populations were significantly higher than those of the southern populations. The migrant population gradually changed the prevalence of the MTHFR C677T polymorphism in Suzhou.

Abstract Objectives The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. Methods Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. Results The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. Conclusions The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

Abstract Gamma knife radiosurgery (GKRS) is recommended as the first-line treatment for brain metastases of lung adenocarcinoma (LUAD) in many guidelines, but its specific mechanism is unclear. We aimed to study the changes in the proteome of brain metastases of LUAD in response to the hyperacute phase of GKRS and further explore the mechanism of differentially expressed proteins (DEPs). Cancer tissues were collected from a clinical trial for neoadjuvant stereotactic radiosurgery before surgical resection of large brain metastases (ChiCTR2000038995). Five brain metastasis tissues of LUAD were collected within 24 h after GKRS. Five brain metastasis tissues without radiotherapy were collected as control samples. Proteomics analysis showed that 163 proteins were upregulated and 25 proteins were downregulated. GO and KEGG enrichment analyses showed that the DEPs were closely related to ribosomes. Fifty-three of 70 ribosomal proteins were significantly overexpressed, while none of them were underexpressed. The risk score constructed from 7 upregulated ribosomal proteins (RPL4, RPS19, RPS16, RPLP0, RPS2, RPS26 and RPS25) was an independent risk factor for the survival time of LUAD patients. Overexpression of ribosomal proteins may represent a desperate response to lethal radiotherapy. We propose that targeted inhibition of these ribosomal proteins may enhance the efficacy of GKRS.

Abstract Background Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship. Methods Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation. Results The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation. Conclusions Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

Abstract Background The weight-adjusted waist index (WWI) is a recently developed obesity metric, and the aim of this study was to investigate the relationship between physical activity (PA) and WWI and the homeostasis model assessment of insulin resistance (HOMA-IR) in adolescents, as well as the joint association of HOMA-IR. Methods This study was based on the National Health and Nutrition Survey conducted between 2013 and 2016 and included 1024 adolescents whose median age was 15.4. Multivariate linear regression was used to examine the associations between HOMA-IR and PA and WWI. Using generalized additive models, a potential nonlinear link between WWI and HOMA-IR was evaluated. Subgroup analysis was also carried out. Results The fully adjusted model revealed a positive association (β: 0.48, 95% CI: 0.43, 0.53) between the WWI and HOMA-IR. The HOMA-IR was lower in physically active (β: -0.16, 95% CI: -0.26, -0.05) participants versus inactive participants. Participants who had higher WWI and were not physically active (β: 0.69; 95% CI: 0.56, 0.82) had the highest levels of HOMA-IR compared to participants who had lower WWI and were physically active. Subgroup analysis revealed that these correlations were similar in males and females. Conclusion Our results demonstrated that higher WWI and PA were associated with a lower HOMA-IR and that WWI and PA had a combined association with HOMA-IR. The findings of this study are informative for the preventing insulin resistance in adolescents.

IntroductionPrevious findings on the association between uric acid (UA) levels and cancer risk are conflicting. Moreover, the mechanisms underlying the interactions between UA levels, fatty acid traits, and cancer outcomes remain complex; it is still unclear whether elevated UA levels influence fatty acid traits and, thereby, contribute to an increased cancer risk. Therefore, we aimed to investigate the association between UA levels and cancer risk, with a specific focus on the potential mediating role of fatty acid traits.MethodsWe employed a Mendelian randomization (MR) analysis utilizing genetic data from large-scale genome-wide association studies to assess the causal relationships among UA levels, fatty acid traits, and cancer risk. The primary method used was the inverse variance-weighted approach alongside Bayesian-weighted Mendelian randomization. Other MR models were also applied for comparison. Sensitivity analyses, based on various statistical assumptions, were also performed to evaluate the robustness of the findings. A two-step MR analysis was conducted to explore the mediating effects of fatty acid traits on the relationship between UA levels and cancer risk.Results and Discussion Elevated UA levels were associated with an increased risk of in situ neoplasms, cervical cancer, and invasive mucinous ovarian cancer, while they were linked to a decreased risk of cancers of the eye and adnexa, small cell lung cancer, bronchus and lung cancer, respiratory system and intrathoracic organ cancers, as well as lung cancer. Mediation analysis revealed that fatty acid traits, particularly the docosahexaenoic acid/trans fatty acid ratio, mediated the relationship between UA levels and lung cancer risk. These findings underscore the potential of fatty acid traits to mediate the association between UA levels and cancer risk, offering new insights for targeted interventions and potentially improving clinical outcomes.

Pseudomonas plecoglossicida is one of the main pathogens causing visceral white spot disease of the large yellow croaker (Pseudosciaena crocea). Although antibiotics are used to control P. plecoglossicida infections, the long-term and large-scale use of antibiotics can lead to the development of drug-resistant bacteria as well as environmental pollution. Therefore, it is necessary to develop novel antibacterial agents to treat P. plecoglossicida infections. In this study, we first developed a two-step-centrifugation method to isolate live and dead P. plecoglossicida cells. Subsequently, we used the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) screening based on inhibition rate to directly isolate antibacterial aptamers from the random library without post-processing. We isolated five antibacterial aptamers, namely B1, B2, B4, B8, and B109, which showed good inhibitory effects against P. plecoglossicida. Among these, B4 showed the highest inhibitory effect (62.40 ± 4.17 %). Further analysis revealed no positive correlation between the inhibitory effect of aptamers and their affinities with the target bacterium. The B4- and B109-binding proteins were isolated from P. plecoglossicida by magnetic separation and sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). Mass spectrometry analysis revealed that the 26 kDa ribosomal protein L2 was the probable B4-binding protein, while the 26 kDa ribosomal protein S3 and 75 kDa ribosomal protein S1 or succinate dehydrogenase flavoprotein subunit were the probable B109-binding proteins. Structural and subcellular localization analyses of these potential B4- and B109-binding proteins were also conducted. Our findings suggest that the inhibitory activity of the antibacterial aptamers against P. plecoglossicida may be mediated via their interaction with the ribosomal proteins, which can interfere with the protein synthesis process in the bacterium, affecting its growth. These findings provide the scientific basis for the development of functional antibacterial aptamers and the elucidation of their mechanisms of action.

Background Inflammation is associated with adverse outcomes of chronic kidney disease (CKD) or chronic heart failure (CHF), but few large data exist. We aimed to explore the clinical associations, and prognostic consequences of inflammation-based scores in patients with CKD and CHF.Methods This work was a retrospective cohort study. Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Nutritional Index (PNI) and Prognostic Index (PI), were used to explore its relationship with CKD progression in patients with CKD stage 1-3b and CHF from the China Renal Data System (CRDS). The composite end point of this study was CKD progression which was defined as eGFR reduction of 40% or progression to end stage renal disease (ESRD).Results Of 8491 patients were enrolled. Kaplan-Meier curve showed that compared to the lower inflammation-based scores, the increased scores have a higher rate of CKD progression, whether in GPS, mGPS, PNI or PI (log-rank test, p 0.05).Conclusions Inflammation-based scores, especially PNI may be a useful clinical biomarker for CKD progression in CKD with CHF patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma, and is closely associated with hepatitis B virus (HBV) infection status and hepatitis B X (HBx) gene integration. This project investigated the cellular biological effects and molecular mechanisms responsible for lymphomagenesis and the progression of HBx integration in DLBCL. The data showed that clinical DLBCL cells demonstrated HBx integration, and the sequencing analysis of integrated sites validated HBx integration in the constructed HBx-transfected cells. Compared with control cells, HBx-transfected cells had a significantly reduced proportion of mitochondrial membrane potential, signals of chromosomal DNA breaks, and proportion of apoptotic cells. Further studies found that this decreased apoptosis level was associated with a significant reduction of cleaved Caspase-3 and downstream poly ADP-ribose polymerase (PARP) proteins, revealing the molecular mechanisms of HBx-associated apoptosis in DLBCL. Animal experiments also demonstrated that the protein expression of cleaved Caspase-3 and PARP was prominently reduced in HBx-transfected cells from subcutaneous tumors in mice. Furthermore, the HBx-integrated cells in clinical tissues had significantly lower cleaved PARP levels than the HBx-negative samples. Therefore, HBx integration inhibits cell apoptosis through the Caspase-3-PARP pathway in DLBCL indicating a potential biomarker and therapeutic target in HBV related DLBCL.