Managing the immune microenvironment of osteosarcoma:the outlook for osteosarcoma treatment

Osteosarcoma,with poor survival after metastasis,is considered the most common primary bone cancer in adolescents.Notwithstanding the efforts of researchers,its five-year survival rate has only shown limited improvement,suggesting that existing therapeutic strategies are insufficient to meet clinical needs.Notably,immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis.Therefore,managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease.Additionally,given the advances in nanomedicine,there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics.Here,we review the classification,characteristics,and functions of the key components of the immune microenvironment in osteosarcoma.This review also emphasizes the application,progress,and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment.Furthermore,we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

Weakness Ranking Method for Subsystems of Heavy-Duty Machine Tools Based on FMECA Information

Heavy-duty machine tools are composed of many subsystems with different functions,and their reliability is governed by the reliabilities of these subsystems.It is important to rank the weaknesses of subsystems and identify the weakest subsystem to optimize products and improve their reliabilities.However,traditional ranking methods based on failure mode effect and critical analysis(FMECA)does not consider the complex maintenance of products.Herein,a weakness ranking method for the subsystems of heavy-duty machine tools is proposed based on generalized FMECA information.In this method,eight reliability indexes,including maintainability and maintenance cost,are considered in the generalized FMECA information.Subsequently,the cognition best worst method is used to calculate the weight of each screened index,and the weaknesses of the subsystems are ranked using a technique for order preference by similarity to an ideal solution.Finally,based on the failure data collected from certain domestic heavy-duty horizontal lathes,the weakness ranking result of the subsystems is obtained to verify the effectiveness of the proposed method.An improved weakness ranking method that can comprehensively analyze and identify weak subsystems is proposed herein for designing and improving the reliability of complex electromechanical products.

Homeostasis of Brassinosteroids Regulated by DRL1, a Putative Acyltransferase in Arabidopsis

Brassinosteroids （BRs） play essential roles in regulating various aspects of plant growth and development and in responding to diverse environmental cues, and their metabolism is an important way to regulate their homeosta-sis in plants. Here, we identified a dominant mutant, dwarf and round leaf-1 （drll-D）, which exhibits weak BR-deficient or BR-insensitive mutant phenotypes, including short and round leaves, prolonged senescence, dwarfed shape, and altered expression levels of the BR-responsive genes. Hypocotyl length and root inhibition assays suggest that the drll-D mutant responds to BRs normally, but has decreased BR signaling outputs. The endogenous levels of several BRs, includ-ing typhasterol （TY）, 6-deoxotyphasterol （6-deoxoTY）, and 6-deoxocastasterone （6-deoxoCS）, are significantly lower in the drll-D mutant than in the wild-type. The DRL1 gene encodes an acyltransferase and is widely expressed in leaves, roots, flowers, and siliques. Plants without DRL1 and its homologs are larger with an enhanced BR signaling. The expres-sion of DRL1 was induced by eBL and inhibited by ABA. DRL1 is involved in the BR metabolism likely by catalyzing the BR conjugation through esterification, which plays important roles in regulating the BR homeostasis and responding to abiotic stresses in Arabidopsis.

A Short Synthesis of Clionamine D

Herein we describe a scalable four-step preparation of a-methylene-y-lactone 3 from steroidal sapogenin. This method allowed a facile synthesis of clionamine D, a natural aminosteroid with potent autophagy bioactivity and unprecedented chemical structure.