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Shaojie Bi,1 Juan Zhang,1 Ning Wei,2 Qingbo Zhou,3,4 Chunyan Wang3 1Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Information Center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Geriatrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 4School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Chunyan Wang, Email 201062013735@email.sdu.edu.cnIntroduction: Anemia, characterized by low hemoglobin or erythrocyte levels, is a significant global health issue with severe implications for public health. Recent studies have explored the potential link between anemia and 25-hydroxyvitamin D [25(OH)D], yet the precise mechanisms remain unclear. This study aims to clarify the possible causal relationship between 25(OH)D levels and anemia risk.Methods: We conducted a comprehensive investigation combining observational and Mendelian randomization (MR) analyses. The observational study included detailed demographic, comorbidities, and laboratory data collected from 7160 hospitalized patients in China. For the MR analysis, genetic polymorphisms were utilized to assess causal effects.Results: Observational analysis revealed an inverse relationship between 25(OH)D levels and the risk of anemia, with stratified analysis indicating a nonlinear association and a threshold of 48.716 nmol/L. The MR analysis confirmed a protective causal relationship between higher 25(OH)D levels and a reduced risk of anemia. Bidirectional MR analysis found no evidence that anemia influences 25(OH)D levels.Discussion: This study provides strong evidence of a causal link between increased 25(OH)D levels and a lower incidence of anemia. The findings highlight the potential role of vitamin D in anemia prevention, supporting the need for further research into vitamin D supplementation as a strategy to reduce anemia risk.Conclusion: Our findings support the hypothesis that higher 25(OH)D levels are causally associated with a reduced risk of anemia, suggesting vitamin D’s potential role in anemia prevention and public health strategies.Keywords: anemia, 25-hydroxyvitamin D, Mendelian randomization

Jing Yang, Chengsen Shu, Xianfu Shang, Hao Xu, Ning Wei Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, People’s Republic of ChinaCorrespondence: Ning Wei, Email weiningjieru2006@163.comPurpose: This study aimed to investigate the prognostic value of systemic immune-inflammation index (SII) in patients with extrahepatic cholangiocarcinoma (EHCC) treated by percutaneous transhepatic biliary stenting (PTBS) combined with 125I seed intracavitary irradiation and further develop a predictive model related to SII.Methods: A total of 145 patients with EHCC who received PTBS combined with 125I seed implantation were retrospectively analyzed. The optimal cut-off value of SII was identified by receiver operating characteristic (ROC) curve analysis. Kaplan–Meier curves and Cox regression were applied to estimate the prognostic value of SII and identify other significant factors of overall survival (OS). Additionally, a novel nomogram was constructed. The concordance index (C-index), calibration plots and decision curve analysis were used to evaluate the performance of the nomogram model.Results: The optimal cut-off value for preoperative SII of 890.2 stratified the patients into High-SII (H-SII) and Low-SII (L-SII) groups. Univariate and multivariate analyses demonstrated that SII was an independent factor for OS. We also found that better therapeutic effect could be obtained with combined postoperative chemotherapy (P < 0.001). Moreover, we revealed that elevated preoperative CA19-9 (P = 0.038) and TBIL level (P = 0.024) were reason for poor prognosis of EHCC. A well-discriminated and calibrated nomogram was developed to predict the 1-year and 2-year OS of EHCC (C-index: 0.709).Conclusion: The SII may be a feasible and convenient prognosis predictor for EHCC. The comprehensive nomogram based on SII presented in this study is a promising model for predicting OS in EHCC patients after PTBS combined with 125I seed intracavitary irradiation.Keywords: extrahepatic cholangiocarcinoma, biliary stenting, 125I seed, systemic immune-inflammation index, nomogram

Premise: Whole-genome duplication (neopolyploidy) can instantly differentiate the phenotype of neopolyploids from their diploid progenitors. These phenotypic shifts in organs such as roots and leaves could also differentiate the way neopolyploids interact with microbial species. While some studies have addressed how specific microbial interactions are affected by neopolyploidy, we lack an understanding of how genome duplication affects the diversity and composition of microbial communities., Methods: We performed a common garden experiment with multiple clones of artificially synthesized autotetraploids and their ancestral diploids, derived from 13 genotypes of wild strawberry, Fragaria vesca. We sequenced epiphytic bacteria and fungi from roots and leaves and characterized microbial communities and leaf functional traits., Results: Autotetraploidy had no effect on bacterial alpha diversity of either organ, but it did have a genotype-dependent effect on the diversity of fungi on leaves. In contrast, autotetraploidy restructured the community composition of leaf bacteria and had a genotype-dependent effect on fungal community composition in both organs. The most differentially abundant bacterial taxon on leaves belonged to the Sphingomonas, while a member of the Trichoderma was the most differentially abundant fungal taxon on roots. Ploidy-induced change in leaf size was strongly correlated with a change in bacterial but not fungal leaf communities., Conclusions: Genome duplication can immediately alter aspects of the plant microbiome, but this effect varies by host genotype and bacterial and fungal community. Expanding these studies to wild settings where plants are exposed continuously to microbes are needed to confirm the patterns observed here., (© 2024 The Authors. American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Visual working memory (VWM) plays a crucial role in temporarily storing and processing visual information, but the nature of stored representations and their interaction with new inputs has long been unclear. The pointer system refers to how VWM links new sensory inputs to stored information using specific cues. This study aimed to investigate whether the pointer system is based on spatial, feature-based, or object-based cues by employing the repetition benefit effect, where memory performance improves with repeated memory items. Across three experiments, we manipulated spatial positions, shapes, and colors as pointer cues to determine how these features affect VWM consolidation and updating. The results showed that while spatial location serves as a strong pointer cue, shape and color features can also effectively reestablish object correspondence in VWM. These findings support the view that the pointer system in VWM is flexible and object-based, utilizing various feature cues to maintain memory continuity. This study provides new insights into how VWM connects new inputs with stored information through the pointer system., (© 2024. The Psychonomic Society, Inc.)

To develop a clean-up material suitable for high-fat food matrices for detecting mycotoxins in yak ghee, an octadecyl-bonded hectorite (Hectorite@NHCO(CH 2 ) 17 CH 3 ) was synthesized through multi-step chemical reactions. A modified QuEChERS-HPLC-MS/MS method for detecting ten mycotoxins in sesame oil in yak ghee was established using Hectorite@NHCO(CH 2 ) 17 CH 3 as clean-up agent. It involved extracting mycotoxin contaminants using acidified acetonitrile and employing the Hectorite@NHCO(CH 2 ) 17 CH 3 to remove interfering substances from the extract. The purified samples were then analyzed using HPLC-MS/MS. Within a linear range of 1.0-500 μg/kg, there was a good linear relationship between the quantification ion peak area of the target analytes and the corresponding concentrations (R 2  ≥ 0.9991). The limit of detection (LOD) ranged from 0.10 μg/kg to 18.62 μg/kg and the limit of quantitation (LOQ) ranged 0.32-62.07 μg/kg. The recoveries at low, medium and high concentrations (25, 100 and 500 μg/kg) ranged from 72.2% to 113.9%, with relative standard deviations (RSD) between 3.2% and 17.5%. The intra-day and inter-day precision met experimental requirements. The proposed method was characterized by a high accuracy and precision, and it could cater to the current demand for detecting ten mycotoxins in yak ghee., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: Pesticide formulations based on nanotechnology can effectively improve the efficiency of pesticide utilization and reduce pesticide residues in the environment. In this study, mesoporous silica nanoparticles containing disulfide bonds were synthesized by the sol-gel method, carboxylated and adsorbed with lufenuron, and grafted with cellulose to obtain a lufenuron-loaded nano-controlled release formulation (Luf@MSNs-ss-cellulose)., Results: The structure and properties of Luf@MSNs-ss-cellulose were characterized. The results showed that Luf@MSNs-ss-cellulose exhibits a regular spherical shape with 12.41% pesticide loading. The highest cumulative release rate (73.46%) of this pesticide-loaded nanoparticle was observed at 7 days in the environment of glutathione and cellulase, which shows redox-enzyme dual-responsive performance. As a result of cellulose grafting, Luf@MSNs-ss-cellulose had a small contact angle and high adhesion work on corn leaves, indicating good wetting and adhesion properties. After 14 days of spraying with 20 mg L -1 formulations in the long-term control efficacy experiment, the mortality of Luf@MSNs-ss-cellulose against Ostrinia furnacalis larvae (56.67%) was significantly higher than that of commercial Luf@EW (36.67%). Luf@MSNs-ss-cellulose is safer for earthworms and L02 cells., Conclusion: The nano-controlled release formulation obtained in this study achieved intelligent pesticide delivery in time and space under the environmental stimulation of glutathione and cellulase, providing an effective method for the development of novel pesticide delivery systems. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Iron is an essential element for microbial survival and secondary metabolism. However, excess iron availability and overloaded secondary metabolites can hinder microbial growth and survival. Microorganisms must tightly control iron homeostasis and secondary metabolism. Our previous studies have found that the stringent starvation protein A (SspA) positively regulates prodiginine biosynthesis by activating iron uptake in Pseudoalteromonas sp. strain R3. It is believed that the interaction between SspA and the small nucleotide ppGpp is important for iron to exert regulation functions. However, the roles of ppGpp in iron absorption and prodiginine biosynthesis, and the underlying relationship between ppGpp and SspA in strain R3 remain unclear. In this study, we found that ppGpp accumulation in strain R3 could be induced by limiting iron. In addition, ppGpp not only positively regulated iron uptake and prodiginine biosynthesis via increasing the SspA level but also directly repressed iron uptake and prodiginine biosynthesis independent of SspA, highlighting the finding that ppGpp can stabilize both iron levels and prodiginine production. Notably, the abolishment of ppGpp significantly increased prodiginine production, thus providing a theoretical basis for manipulating prodiginine production in the future. This dynamic ppGpp-mediated interaction between iron uptake and prodiginine biosynthesis has significant implications for understanding the roles of nutrient uptake and secondary metabolism for the survival of bacteria in unfavorable environments., (© 2024 John Wiley & Sons Ltd.)

Dadi Xie,1,&ast; Fengfeng Li,1,&ast; Deshui Pang,1 Shiyuan Zhao,2 Meihua Zhang,1 Zhongfa Ren,1 Chunmei Geng,2 Changshui Wang,3 Ning Wei,4 Pei Jiang2 1Tengzhou Central People’s Hospital, Tengzhou, 277500, People’s Republic of China; 2Jining First People’s Hospital, Jining Medical University, Jining, 272000, People’s Republic of China; 3Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272000, People’s Republic of China; 4Shanting District People’s Hospital, Zaozhuang, 277200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meihua ZhangTengzhou Central People’s Hospital, Xingtan Road, Tenzhou, 277500, People’s Republic of ChinaTel/Fax +86 0632-5512227Email meihua_zhang@126.comPei JiangJining First People’s Hospital, Jning Medical University, Jiankang Road, Jining, 272000, People’s Republic of ChinaTel/Fax + 86 0537-2106208Email jiangpeicsu@sina.comPurpose: Inflammatory bowel diseases (IBD) are a chronic inflammatory disease, which affects almost all tissues in the body. Previous studies mainly focused on breathing, fecal, and urine samples of patients with IBD. However, there is no comprehensive metabolomic analysis of the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues. Therefore, the aim of our study is to evaluate the utility metabolomic analysis of target tissues in the pathogenesis of IBD in exploring new biomarkers for early diagnosis and treatment.Methods: Male Sprague–Dawley rats were randomly allocated to control and DSS-treated groups (n = 7). Dextran sulfate sodium (DSS) was orally administered for 6 weeks. Gas chromatography-mass spectrometry (GC-MS) was used for metabolite determination, multivariate statistical analysis was used to identify metabolites that were differentially expressed in two groups.Results: Our results showed that 3, 11, 12, 6, 5, 13, 13, and 11 metabolites were differentially expressed between the DSS treatment group and the control group in the serum, colon, heart, liver, kidney, cortex, hippocampus, and brown fat tissues, respectively. The most significant change of metabolites in the study was amino acid (L-alanine, L-glutamic acid, L-phenylalanine, L-proline, L-lysine, L-isoleucine, L-tryptophan, L-norleucine, L-valine, glycine, serine, L-threonine), organic acid (citric acid, 3-hydroxybutyric acid, propanoic acid), glucide (D-arabinose, D-fructose) and purine (9H-purin-6-ol, D-ribose) profiles. Several pathways were affected according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as alanine, aspartate, and glutamate metabolism, glutathione metabolism) to purine metabolism (aminoacyl-tRNA biosynthesis).Conclusion: Using GC-MS-based profiling of metabolite changes, these results may provide a more comprehensive view for IBD and IBD-related diseases and improve the understanding of IBD pathogenesis.Keywords: inflammatory bowel disease, metabolite, GC-MS, dextran sodium sulfate, biomarker

ObjectiveEvaluate the efficacy and safety/tolerability of cryoneurolysis for reduction of pain and symptoms associated with knee osteoarthritis (OA).DesignRandomized, double-blind, sham-controlled, multicenter trial with a 6-month follow-up in patients with mild-to-moderate knee OA. Patients were randomized 2:1 to cryoneurolysis targeting the infrapatellar branch of the saphenous nerve (IPBSN) or sham treatment. The primary endpoint was the change from baseline to Day 30 in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain score adjusted by the baseline score and site. Secondary endpoints, including visual analogue scale (VAS) pain score and total WOMAC score, were tested in a pre-defined order.ResultsThe intent-to-treat (ITT) population consisted of 180 patients (n = 121 active treatment, n = 59 sham treatment). Compared to the sham group, patients who received active treatment had a statistically significant greater change from baseline in the WOMAC pain subscale score at Day 30 (P = 0.0004), Day 60 (P = 0.0176), and Day 90 (P = 0.0061). Patients deemed WOMAC pain responders at Day 120 continued to experience a statistically significant treatment effect at Day 150. Most expected side effects were mild in severity and resolved within 30 days. The incidence of device- or procedure-related adverse events was similar in the two treatment groups with no occurrence of serious or unanticipated adverse device effects (ADE).ConclusionsCryoneurolysis of the IPBSN resulted in statistically significant decreased knee pain and improved symptoms compared to sham treatment for up to 150 days, and appeared safe and well tolerated.

The escalating threat of healthcare-associated infections highlights the urgent need for biocompatible antibacterial materials that effectively combat drug-resistant pathogens. In this study, we present a novel fabrication method for triple-helical recombinant collagen-silver hybrid nanofibers, specifically designed for anti-Methicillin-Resistant Staphylococcus aureus (MRSA) applications. Utilizing a silver-mediated crosslinking strategy, we harness a low-power 38 W lamp to enable silver ions (Ag+) to mediate crosslinking across various proteins. Mechanistic insights reveal the pivotal role of nine amino acids in facilitating this reaction. The triple-helical recombinant collagen (THRC) maintains its native structure, forming well-ordered nanofibers, while other globular proteins form a distinctive network-like structure. THRC also serves as a reducing and dispersing agent, facilitating the in situ synthesis of highly dispersed silver nanoparticles (AgNPs) (~7 nm in diameter) within the nanofibers. Systematic investigation of the reaction conditions between THRC and Ag+ demonstrates the versatility of this novel approach for nanofiber fabrication. The incorporation of AgNPs imparts exceptional antibacterial activity to the THRC/AgNPs nanofibers, exhibiting a minimum inhibitory concentration (MIC) of 19.2 mg/L and a minimum bactericidal concentration (MBC) of 153.6 mg/L against MRSA. This innovative approach holds significant potential for developing antibacterial protein-based biomaterials for infection management in wound healing and other biomedical applications.&#xD;&#xD;&#xD., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The inherent large HOMO-LUMO gap of alkyl thiol (CnS) self-assembled monolayers (SAMs) has limited their application in molecular electronics. This work demonstrates significant enhancement of mechano-electrical sensitivity in CnS SAMs by external compression, achieving a gauge factor (GF) of approximately 10 for C10S SAMs. This GF surpasses values reported for conjugated wires and DNA strands, highlighting the potential of CnS SAMs in mechanosensitive devices. Conductive atomic force microscopy (cAFM) investigations reveal a strong dependence of GF on the alkyl chain length in probe/CnS/Au junctions. This dependence arises from the combined influence of molecular tilting and probe penetration, facilitated by the low Young's modulus of alkyl chains. Theoretical simulations corroborate these findings, demonstrating a shift in the electrode Fermi level toward the molecular resonance region with increasing chain length and compression. Introducing a rigid graphene interlayer prevents probe penetration, resulting in a GF that is largely independent of the alkyl chain length. This highlights the critical role of probe penetration in maximizing mechano-electrical sensitivity. These findings pave the way for incorporating CnS SAMs into mechanosensitive and mechanocontrollable molecular electronic devices, including touch-sensitive electronic skin and advanced sensor technologies. This work demonstrates the potential of tailoring mechanical and electrical properties of SAMs through molecular engineering and interface modifications for optimized performance in specific applications.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown potential as a therapeutic option for lupus nephritis (LN), particularly in patients refractory to conventional treatments. Despite extensive translational research on MSCs, the precise mechanisms by which MSCs migrate to the kidney and restore renal function remain incompletely understood. Here, we aim to clarify the spatiotemporal characteristics of hUC-MSC migration into LN kidneys and their interactions with host cells in microenvironment. This study elucidates that the migration of hUC-MSCs to the LN kidney is driven by elevated levels of CXCL10, predominantly produced by glomerular vascular endothelial cells through the IFN-γ/IRF1-KPNA4 pathway. Interestingly, the blockade of CXCL10-CXCR3 axis impedes the migration of hUC-MSCs to LN kidney and negatively impacts therapeutic outcomes. Single cell-RNA sequencing analysis underscores the importance of this axis in mediating the regulatory effects of hUC-MSCs on the renal immune environment. Furthermore, hUC-MSCs have been observed to induce and secrete interleukin 4 inducible gene 1 (IL4I1) in response to the microenvironment of LN kidney, thereby suppressing Th1 cells. Genetically ablating IL4I1 in hUC-MSCs abolishes their therapeutic effects and prevents the inhibition of CXCR3 + Th1 cell infiltration into LN kidneys. This study provides valuable insights into the significant involvement of CXCL10-CXCR3 axis in hUC-MSC migration to the LN kidneys and the subsequent remodeling of renal immune microenvironment. Regulating the CXCL10-CXCR3 axis and IL4I1 secretion may be developed as a novel therapeutic strategy to improve treatment outcomes of LN., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)