Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Theta burst stimulation (TBS) is more energy- and time-efficient than is standard repetitive transcranial magnetic stimulation (rTMS). However, further studies are needed to analyze TBS therapy for its efficacy and safety compared with standard rTMS in treating depression. The aim of this meta-analysis was to compare TBS therapy with standard rTMS treatment regarding their safety and therapeutic effect on individuals with depression. MATERIALS AND METHODS: Six data bases (Wanfang, the China National Knowledge Infrastructure, PubMed, Embase, Cochrane Library, and PsycINFO) were searched from inception till December 20, 2022. Two independent reviewers selected potentially relevant studies on the basis of the inclusion criteria, extracted data, and evaluated the methodologic quality of the eligible trials using the modified ten-item Physiotherapy Evidence Database scale per Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Finally, ten comparable pairs of nine randomized controlled trials (RCTs) were included for meta-analysis. Summary odds ratios (ORs) of the rates of response, remission, and adverse events were simultaneously calculated using quality-effects (QE) and random-effects (RE) models. Changes in depression scores associated with antidepressant effects were expressed using standardized mean differences simultaneously. This study was registered with the International Prospective Register of Systematic Reviews (CRD42022376790). RESULTS: Nine of the 602 RCTs, covering 1124 patients (616 who had TBS protocols applied vs 508 treated using standard rTMS), were included. Differences in response rates between the above two treatment modalities were not significant (OR = 1.01, 95% CI: 0.88-1.16, p = 0.44, I2 = 0%, RE model; OR = 1.07, 95% CI: 0.87-1.32, p = 0.44, I2 = 0%, QE model). Differences in adverse event rates between TBS and standard rTMS groups were not statistically significant. CONCLUSIONS: TBS has similar efficacy and safety to standard rTMS for treating depression. Considering the short duration of daily stimulation sessions, this meta-analysis supports the continued development of TBS for treating depression.

Functional Identification and Structural Analysis of a New Lipoate Protein Ligase in Mycoplasma hyopneumoniae.

Mycoplasma hyopneumoniae (M. hyopneumoniae) is the causative agent of pandemic pneumonia among pigs, namely, swine enzootic pneumonia. Although M. hyopneumoniae was first identified in 1965, little is known regarding its metabolic pathways, which might play a pivotal role during disease pathogenesis. Lipoate is an essential cofactor for enzymes important for central metabolism. However, the lipoate metabolism pathway in M. hyopneumoniae is definitely unclear. Here, we identified a novel gene, lpl, encoding a lipoate protein ligase in the genome of M. hyopneumoniae (Mhp-Lpl). This gene contains 1,032 base pairs and encodes a protein of 343 amino acids, which is between 7.5 and 36.09% identical to lipoate protein ligases (Lpls) of other species. Similar to its homologs in other species, Mhp-Lpl catalyzes the ATP-dependent activation of lipoate to lipoyl-AMP and the transfer of the activated lipoyl onto the lipoyl domains of M. hyopneumoniae GcvH (Mhp H) in vitro. Enzymatic and mutagenesis analysis indicate that residue K56 within the SKT sequence of Mhp H protein is the lipoyl moiety acceptor site. The three-dimensional structure showed typical lipoate protein ligase folding, with a large N-terminal domain and a small C-terminal domain. The large N-terminal domain is responsible for the full enzymatic activity of Mhp-Lpl. The identification and characterization of Mhp-Lpl will be beneficial to our understanding of M. hyopneumoniae metabolism. Summary: Lipoic acid is an essential cofactor for the activation of some enzyme complexes involved in key metabolic processes. Lipoate protein ligases (Lpls) are responsible for the metabolism of lipoic acid. To date, little is known regarding the Lpls in M. hyopneumoniae. In this study, we identified a lipoate protein ligase of M. hyopneumoniae. We further analyzed the function, overall structure and ligand-binding site of this protein. The lipoate acceptor site on M. hyopneumoniae GcvH was also identified. Together, these findings reveal that Lpl exists in M. hyopneumoniae and will provide a basis for further exploration of the pathway of lipoic acid metabolism in M. hyopneumoniae.

A Novel Lipoate-Protein Ligase, Mhp-LplJ, Is Required for Lipoic Acid Metabolism in Mycoplasma hyopneumoniae.

Lipoic acid is a conserved cofactor necessary for the activation of several critical enzyme complexes in the aerobic metabolism of 2-oxoacids and one-carbon metabolism. Lipoate metabolism enzymes are key for lipoic acid biosynthesis and salvage. In this study, we found that Mycoplasma hyopneumoniae (M. hyopneumoniae) Mhp-Lpl, which had been previously shown to have lipoate-protein ligase activity against glycine cleavage system H protein (GcvH) in vitro, did not lipoylate the lipoate-dependent subunit of dihydrolipoamide dehydrogenase (PdhD). Further studies indicated that a new putative lipoate-protein ligase in M. hyopneumoniae, MHP_RS00640 (Mhp-LplJ), catalyzes free lipoic acid attachment to PdhD in vitro. In a model organism, Mhp-LplJ exhibited lipoate and octanoate ligase activities against PdhD. When the enzyme activity of Mhp-LplJ was disrupted by lipoic acid analogs, 8-bromooctanoic acid (8-BrO) and 6,8-dichlorooctanoate (6,8-diClO), M. hyopneumoniae growth was arrested in vitro. Taken together, these results indicate that Mhp-LplJ plays a vital role in lipoic acid metabolism of M. hyopneumoniae, which is of great significance to further understand the metabolism of M. hyopneumoniae and develop new antimicrobials against it.