Anterior cruciate ligament injury should not be considered a contraindication for medial unicompartmental knee arthroplasty: Finite element analysis.

PURPOSE: The research objective of this study is to use finite element analysis to investigate the impact of anterior cruciate ligament (ACL) injury on medial unicompartmental knee arthroplasty (UKA) and explore whether patients with ACL injuries can undergo UKA. METHODS: Based on the morphology of the ACL, models of ACL with diameters ranging from 1 to 10mm are created. Finite element models of UKA include ACL absence and ACLs with different diameters. After creating a complete finite element model and validating it, four different types of loads are applied to the knee joint. Statistical analysis is conducted to assess the stress variations in the knee joint structure. RESULTS: A total of 11 finite element models of UKA were established. Regarding the stress on the ACL, as the diameter of the ACL increased, when a vertical load of 750N was applied to the femur, combined with an anterior tibial load of 105N, the stress on the ACL increased from 2.61 MPa to 4.62 MPa, representing a 77.05% increase. Regarding the equivalent stress on the polyethylene gasket, a notable high stress change was observed. The stress on the gasket remained between 12.68 MPa and 14.33 MPa in all models. the stress on the gasket demonstrated a decreasing trend. The equivalent stress in the lateral meniscus and lateral femoral cartilage decreases, reducing from the maximum stress of 4.71 MPa to 2.61 MPa, with a mean value of 3.73 MPa. This represents a reduction of 44.72%, and the statistical significance is (P < 0.05). However, under the other three loads, there was no significant statistical significance (P > 0.05). CONCLUSION: This study suggests that the integrity of the ACL plays a protective role in performing medial UKA. However, this protective effect is limited when performing medial UKA. When the knee joint only has varying degrees of ACL injury, even ACL rupture, and the remaining structures of the knee joint are intact with anterior-posterior stability in the knee joint, it should not be considered a contraindication for medial UKA.

The central helicase domain holds the major conformational epitopes of melanoma differentiation-associated gene 5 autoantibodies.

OBJECTIVES: Autoantibodies against MDA5 serve as a biomarker for dermatomyositis (DM) and a risk factor for interstitial lung disease (ILD). MDA5 is a protein responsible for sensing RNA virus infection and activating signalling pathways against it. However, little is known about antigen epitopes on MDA5 autoantibodies. We aimed to determine the interaction of the MDA5 autoantibody-antigen epitope. METHODS: Cell-based assays (CBAs), immunoprecipitation-immunoblot assays, and various immunoblotting techniques were used in the study. RESULTS: We demonstrate that DM patient autoantibodies recognize MDA5 epitopes in a native conformation-dependent manner. Furthermore, we identified the central helicase domain formed by Hel1, Hel2i, Hel2, and pincer (3Hel) as the major epitopes. As proof of principle, the purified 3Hel efficiently absorbed MDA5 autoantibodies from patient sera through immunoprecipitation-immunoblot assay. CONCLUSION: Our study uncovers the nature of antigen epitopes on MDA5 and provides guidance for diagnosis and targeted therapeutic approach development.

A novel rare variant of CNPY3 from familial NMOSD impairs the TLR-mediated immune response.

Toll-like receptors (TLRs) are a class of proteins that play essential roles in innate and adaptive immune responses. Recently, accumulating evidence has demonstrated that impairments in the TLR signalling pathway contribute to the development and progression of neuroimmune diseases, such as neuromyelitis optica spectrum disorder (NMOSD). However, the cellular and molecular mechanisms are still largely unknown. In this study, we report a novel variant, C52Y, of canopy FGF signalling regulator 3 (CNPY3) from patients with familial NMOSD and demonstrate that this variant shows a stronger interaction with GP96 and TLRs than with wild-type CNPY3. We find that C52Y has dominant negative effects on TLR4 surface expression. Importantly, the TLR4 surface expression level is decreased in RAW264.7 cells infected with the C52Y virus upon LPS stimulation. We further demonstrate that bone marrow-derived macrophages (BMDMs) from CNPY3C52Y/+ transgenic mice secrete less tumour necrosis factor (TNF) and interleukin (IL)-6 than BMDMs from wild-type mice upon stimulation with LPS. These data suggest that impairment of TLR trafficking may contribute to the development of neuroimmune disorders.

Enzyme-Enhanced Codelivery of Doxorubicin and Bcl-2 Inhibitor by Electrospun Nanofibers for Synergistic Inhibition of Prostate Cancer Recurrence.

One of the great challenges of postoperative prostate cancer management is tumor recurrence. Although postoperative chemotherapy presents benefits to inhibit unexpected recurrence, it is still limited due to the drug resistance or intolerable complications of some patients. Electrospun nanofiber, as a promising drug carrier, demonstrating sustained drug release behavior, can be implanted into the tumor resection site during surgery and is conductive to tumor inhibition. Herein, we fabricated electrospun nanofibers loaded with doxorubicin (DOX) and ABT199 to synergistically prevent postoperative tumor recurrence. Enzymatic degradation of the biodegradable electrospun nanofibers facilitated the release of the two drugs. The primarily released DOX from the electrospun nanofibers effectively inhibited tumor recurrence. However, the sustained release of DOX led to drug resistance of the tumor cells, yielding unsatisfactory eradication of the residual tumor. Remarkably, the combined administration of DOX and ABT199, simultaneously released from the nanofibers, not only prolonged the chemotherapy by DOX but also overcame the drug resistance via inhibiting the Bcl-2 activation and thereby enhancing the apoptosis of tumor cells by ABT199. This dual-drug-loaded implant system, combining efficient chemotherapy and anti-drug resistance, offers a prospective strategy for the potent inhibition of postoperative tumor recurrence.

Tianweitania sediminis gen. nov., sp. nov., a member of the family Phyllobacteriaceae, isolated from subsurface sediment core.

A bacterial strain, designated Z8T, was isolated from the terrestrial sediment of the Mohe Basin in north-east China. Phylogenetic analyses of 16S rRNA genes showed that this strain belonged to the family Phyllobacteriaceae, and was most closely related to Phyllobacterium bourgognense, with a sequence similarity of 96.9 %. The major cellular fatty acids were summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major respiratory quinone was ubiquinone-10. The three major polar lipids of strain Z8T consisted of glycolipids, phosphatidylethanolamine and phosphatidylmethylethanolamine. The DNA G+C content was 59.6 mol%. The chemotaxonomic characteristics of strain Z8T differed in some respects from those of members of the family Phyllobacteriaceae. Based on phylogenetic, phenotypic and chemotaxonomic data, strain Z8T is considered to represent a novel species of a novel genus within the family Phyllobacteriaceae, for which the name Tianweitania sediminis gen. nov., sp. nov. is proposed. The type strain is Z8T ( = CGMCC 1.12944T = JCM 30358T).

Qipengyuania sediminis gen. nov., sp. nov., a member of the family Erythrobacteraceae isolated from subterrestrial sediment.

A Gram-reaction-negative, non-motile, facultatively aerobic bacterium, designated strain M1T, was isolated from a subterrestrial sediment sample of Qiangtang Basin in Qinghai-Tibetan plateau, China. The strain formed rough yellow colonies on R2A plates. Cells were oval or short rod-shaped, catalase-positive and oxidase-negative. Phylogenetic analyses based on 16S rRNA gene sequences indicated that the isolate belonged to the family Erythrobacteraceae and showed 96.2­96.4 % 16S rRNA gene sequence similarities to its closest relatives. Chemotaxonomic analysis revealed ubiquinone-10 (Q10) as the dominant respiratory quinone of strain M1T and C17 : 1ω6c (44.2 %) and C18 : 1ω7c (13.7 %) as the major fatty acids. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, sphingoglycolipid, three unidentified glycolipids, one unidentified phosphoglycolipid and one unidentified lipid. The DNA G+C content of strain M1T was 73.7 mol%. On the basis of phenotypic, phylogenetic and genotypic data presented in this study, strain M1T represents a novel species of a new genus in the family Erythrobacteraceae, for which the name Qipengyuania sediminis gen. nov., sp. nov. is proposed. The type strain of the type species is M1T ( = CGMCC 1.12928T = JCM 30182T).