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Additional file 5. Data analysis results.

Additional file 3. Table S3 Regression coefficients of cuproptosis-related lncRNAs determined via multi-Cox analysis.

Additional file 1: Fig. S1. Protein expression of the protein homeostasis signaling pathway by western blot in soleus muscles of the hindlimb unloading model mice, fully uncropped and unprocessed images for Fbx32 (MAFbx), GAPDH, LC3B and GAPDH blot are listed. Fig. S2. Shows the definition of "3HB-regulated genes" (related to Fig. 3). Fig. S3. Shows principal component analysis (PCA) of whole transcriptome data and KEGG pathway of “3HB-regulated genes”, the transcript abundance changes of selected genes (in FPKM) and the results of real-time PCR analysis for Atg9, Vps13d, and Chac1 are also listed. Fig. S4. Shows protein expression of the Akt/FoxO3a and mTOR/4E-BP1 pathways by western blot in soleus muscles of the hindlimb unloading model mice, fully uncropped and unprocessed images for each blot are listed. Fig. S5. Shows relative abundance changes of glycine, neurotransmitters and metabolites of glycolysis and TCA cycle. Fig. S6. Shows the blood glucose and blood ketones in the HU model mice.

Meimei Tian,1,2,* Zihua Li,1,* Xujuan Chen,1 Qiting Wu,1 Huimin Shi,1 Yuchang Zhu,1 Yan Shi2 1Department of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Nursing, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Shi, Tel +86 21 66307304, Fax +86 21 66307542, Email shi_yan2018@outlook.comBackground: Pain relief is the most important issue in the long-term outcome of arthroplasty surgery, with nearly one-third of patients still suffered persistent pain and caused dissatisfaction after the surgery.Methods: A total of 713 patients underwent primary elective primary TKA and UKA were included consecutively between July 2018 and December 2019, using binary logistic method to analyze the data.Results: The prevalence of CPSP at rest and on movement at 2-year was 12.1% and 37.7% respectively after primary knee arthroplasty and CPSP at rest factors included: age above 80 (odds ratio [OR]= 6.72, 95% confidence interval [CI] 1.58 to 28.56), BMI above 30 (2.339, 1.02 to 5.383), and moderate to severe pain variables: preoperative pain, (1.95, 1.11 to 3.41); APSP on movement, 4.9 (2.31– 10.6); and follow-up contralateral knee pain-at-rest scores (12.6, 5.5 to 28.5). Factors associated with presence of CPSP on movement included: no smoking (2.59, 1.07 to 6.26); and moderate to severe pain variables: preoperative pain, (1.57, 1.073 to 2.30); APSP at rest, (1.85, 1.13 to 3.02); APSP on movement, 6.11 (3.82 to 9.78); and follow-up contralateral knee pain-on-movement scores, 3.22 (2.08 to 5.00). Factors to occurrence of moderate to severe CPSP on movement include: presence of COPD (12.20, 2.19 to 67.98); and moderate to severe pain variables: preoperative pain (2.36, 1.32 to 4.23); APSP on movement (4.68, 1.95 to 11.25); and follow-up contralateral knee pain-on-movement scores (2.71, 1.66 to 4.42).Conclusion: Prevention strategies should be targeted to different types of pain, and the comorbidity of COPD undergoing knee arthroplasty should receive early identification and attention.Keywords: chronic postsurgical pain, acute-postoperative pain, total knee arthroplasty, rest pain, movement pain

Colitis is a common disease of the colon that is very difficult to treat. Probiotic bacteria could be an effective treatment. The probiotic Escherichia coli Nissle 1917 (EcN) was engineered to synthesize the ketone body (R)-3-hydroxybutyrate (3HB) for sustainable production in the gut lumen of mice suffering from colitis. Components of heterologous 3HB synthesis routes were constructed, expressed, optimized, and inserted into the EcN genome, combined with deletions in competitive branch pathways. The genome-engineered EcN produced the highest 3HB level of 0.6 g/L under microaerobic conditions. The live therapeutic was found to colonize the mouse gastrointestinal tract over 14 days, elevating gut 3HB and short-chain-length fatty acid (SCFA) levels 8.7- and 3.1-fold compared to those of wild-type EcN, respectively. The sustainable presence of 3HB in mouse guts promoted the growth of probiotic bacteria, especially Akkermansia spp., to over 31% from the initial 2% of all the microbiome. As a result, the engineered EcN termed EcNL4 ameliorated colitis induced via dextran sulfate sodium (DSS) in mice. Compared to wild-type EcN or oral administration of 3HB, oral EcNL4 uptake demonstrated better effects on mouse weights, colon lengths, occult blood levels, gut tissue myeloperoxidase activity and proinflammatory cytokine concentrations. Thus, a promising live bacterium was developed to improve colonic microenvironments and further treat colitis. This proof-of-concept design can be employed to treat other diseases of the colon.

Additional file 2: Clinical Indicators and Clinical Symptoms Associated with Respiratory Viruses Negative.