Engineering a Self-Assembled Protein Cage for Targeted Dual Functionalization.

Self-assembled protein cages are attractive scaffolds for organizing various proteins of interest (POIs) toward applications in synthetic biology and medical science. However, specifically attaching multiple POIs to a single protein cage remains challenging, resulting in diversity among the functionalized particles. Here, we present the engineering of a self-assembled protein cage, DTMi3ST, capable of independently recruiting two different POIs using SpyCatcher (SC)/SpyTag (ST) and DogCatcher (DC)/DogTag (DT) chemistries, thereby reducing variability between assemblies. Using fluorescent proteins as models, we demonstrate controlled targeting of two different POIs onto DTMi3ST protein cages both in vitro and inside living cells. Furthermore, dual functionalization of the DTMi3ST protein cage with a membrane-targeting peptide and ß-galactosidase resulted in the construction of membrane-bound enzyme assemblies in Escherichia coli, leading to a 69.6% enhancement in substrate utilization across the membrane. This versatile protein cage platform provides dual functional nanotools for biological and biomedical applications.

The impact of physical therapy on dysphagia in neurological diseases: a review.

A neurogenic dysphagia is dysphagia caused by problems with the central and peripheral nervous systems, is particularly prevalent in conditions such as Parkinson's disease and stroke. It significantly impacts the quality of life for affected individuals and causes additional burdens, such as malnutrition, aspiration pneumonia, asphyxia, or even death from choking due to improper eating. Physical therapy offers a non-invasive treatment with high efficacy and low cost. Evidence supporting the use of physical therapy in dysphagia treatment is increasing, including techniques such as neuromuscular electrical stimulation, sensory stimulation, transcranial direct current stimulation, and repetitive transcranial magnetic stimulation. While initial studies have shown promising results, the effectiveness of specific treatment regimens still requires further validation. At present, there is a lack of scientific evidence to guide patient selection, develop appropriate treatment regimens, and accurately evaluate treatment outcomes. Therefore, the primary objectives of this review are to review the results of existing research, summarize the application of physical therapy in dysphagia management, we also discussed the mechanisms and treatments of physical therapy for neurogenic dysphagia.

Achieving Negatively Charged Pt Single Atoms on Amorphous Ni(OH)2 Nanosheets with Promoted Hydrogen Absorption in Hydrogen Evolution.

Single-atom (SA) catalysts with nearly 100% atom utilization have been widely employed in electrolysis for decades, due to the outperforming catalytic activity and selectivity. However, most of the reported SA catalysts are fixed through the strong bonding between the dispersed single metallic atoms with nonmetallic atoms of the substrates, which greatly limits the controllable regulation of electrocatalytic activity of SA catalysts. In this work, Pt-Ni bonded Pt SA catalyst with adjustable electronic states was successfully constructed through a controllable electrochemical reduction on the coordination unsaturated amorphous Ni(OH)2 nanosheet arrays. Based on the X-ray absorption fine structure analysis and first-principles calculations, Pt SA was bonded with Ni sites of amorphous Ni(OH)2, rather than conventional O sites, resulting in negatively charged Ptδ-. In situ Raman spectroscopy revealed that the changed configuration and electronic states greatly enhanced absorbability for activated hydrogen atoms, which were the essential intermediate for alkaline hydrogen evolution reaction. The hydrogen spillover process was revealed from amorphous Ni(OH)2 that effectively cleave the H-O-H bond of H2O and produce H atom to the Pt SA sites, leading to a low overpotential of 48 mV in alkaline electrolyte at -1000 mA cm-2 mg-1Pt, evidently better than commercial Pt/C catalysts. This work provided new strategy for the controllable modulation of the local structure of SA catalysts and the systematic regulation of the electronic states.

Unraveling the distinction between depression and anxiety: A machine learning exploration of causal relationships.

OBJECTIVE: Depression and anxiety, prevalent coexisting mood disorders, pose a clinical challenge in accurate differentiation, hindering effective healthcare interventions. This research addressed this gap by employing a streamlined Symptom Checklist 90 (SCL-90) designed to minimize patient response burden. Utilizing machine learning algorithms, the study sought to construct classification models capable of distinguishing between depression and anxiety. METHODS: The study included 4262 individuals currently experiencing depression alone (n = 2998), anxiety alone (n = 716), or both depression and anxiety (n = 548). Counterfactual diagnosis was used to construct a causal network on the dataset. Employing a causal network, the SCL-90 was simplified. Items that have causality with only depression, only anxiety and both depression and anxiety were selected, and these streamlined items served as input features for four distinct machine learning algorithms, facilitating the creation of classification models for distinguishing depression and anxiety. RESULTS: Cross-validation demonstrated the performance of the classification models with the following metrics: (1) K-nearest neighbors (AUC = 0.924, Acc = 92.81 %); (2) support vector machine (AUC = 0.937, Acc = 94.38 %); (3) random forest (AUC = 0.918, Acc = 94.38 %); and (4) adaptive boosting (AUC = 0.882, Acc = 94.38 %). Notably, the support vector machine excelled, with the highest AUC and superior accuracy. CONCLUSION: Incorporating the simplified SCL-90 and machine learning presents a promising, efficient, and cost-effective tool for the precise identification of depression and anxiety.

Dynamic Metabolons Using Stimuli-Responsive Protein Cages.

Naturally evolved metabolons have the ability to assemble and disassemble in response to environmental stimuli, allowing for the rapid reorganization of chemical reactions in living cells to meet changing cellular needs. However, replicating such capability in synthetic metabolons remains a challenge due to our limited understanding of the mechanisms by which the assembly and disassembly of such naturally occurring multienzyme complexes are controlled. Here, we report the synthesis of chemical- and light-responsive protein cages for assembling synthetic metabolons, enabling the dynamic regulation of enzymatic reactions in living cells. Particularly, a chemically responsive domain was fused to a self-assembled protein cage subunit, generating engineered protein cages capable of displaying proteins containing cognate interaction domains on their surfaces in response to small molecular cues. Chemical-induced colocalization of sequential enzymes on protein cages enhances the specificity of the branched deoxyviolacein biosynthetic reactions by 2.6-fold. Further, by replacing the chemical-inducible domain with a light-inducible dimerization domain, we created an optogenetic protein cage capable of reversibly recruiting and releasing targeted proteins onto and from the exterior of the protein cages in tens of seconds by on-off of blue light. Tethering the optogenetic protein cages to membranes enables the formation of light-switchable, membrane-bound metabolons, which can repeatably recruit-release enzymes, leading to the manipulation of substrate utilization across membranes on demand. Our work demonstrates a powerful and versatile strategy for constructing dynamic metabolons in engineered living cells for efficient and controllable biocatalysis.

Submicron-Thickness Ultraflexible Organic Light-Emitting Diodes via a Photoregulated Stripping Strategy.

With the rapid advances in imperceptible and epidermal electronics, the research on ultraflexible organic light-emitting diodes (OLEDs) has become increasingly significant, owing to their excellent flexibility and conformability to the human body. It is highly desirable to develop submicrometer-thick ultraflexible OLEDs to enable the devices to seamlessly conform to the surface of arbitrary-shaped objects and still function properly. However, it remains a huge challenge for currently reported OLEDs due to the lack of an appropriate stripping strategy. Here, for the first time, we develop a facile photoregulated stripping strategy for the fabrication of high-performance ultraflexible OLEDs with submicron thickness. Under ultraviolet (UV) irradiation, the surface adhesion force of the ultrathin photopolymer membrane can be adjusted from 16.9 to 5.1 N/m, thereby effectively controlling the laminating and detaching process. Based on this strategy, the resultant device thickness is as low as 0.821 µm, which is the lowest record among flexible OLEDs reported to date. More remarkably, excellent electrical properties with a maximum current efficiency (CE) of 62.5 cd/A, an external quantum efficiency (EQE) of 17.8%, and a low turn-on voltage of 2.5 V are realized, which are superior to almost all of the reported ultraflexible OLEDs with thicknesses below 10 µm. Based on versatile ultraflexible OLEDs, all-organic and skin-mounted displays are successfully realized by employing a conformable organic thin-film transistor (OTFT) as the driver. This work offers a feasible strategy for advancing OLEDs from flexible to ultraflexible, showing significant application potential in future epidermal electronics and conformal displays.

Low-Frequency Evolution Mechanism of Customized HEAs-Based Electromagnetic Response Modes Manipulated by Carbothermal Shock.

An emerging carbothermal shock method is an ultra-convenient strategy for synthesizing high-entropy alloys (HEAs), in which the intelligent combination of carbon support and HEAs can be serve as a decisive factor for interpreting the trade-off relationship between conductive gene and dielectric gene. However, the feedback mechanism of HEAs ordering degree on electromagnetic (EM) response in 2-18 GHz has not been comprehensively demystified. Herein, while lignin-based carbon fiber paper (L-CFP) as carbon support, L-CFP/FeCoNiCuZn-X with is prepared by carbothermal shock method. The reflection loss of -82.6 dB with thickness of 1.31 mm is achieved by means of pointing electron enrichment within L-CFP/FeCoNiCuZn HEAs heterointerfaces verified by theoretical calculations. Simultaneously, low-frequency evolution with high-intensity and broadband EM response relies on a "sacrificing" strategy achieved by construction of polymorphic L-CFP/semi-disordered-HEAs heterointerfaces. The practicality of L-CFP/FeCoNiCuZn-X in complex environments is given prominence to thermal conductivity, hydrophobicity, and electrocatalytic property. This work is of great significance for insightful mechanism analysis of HEAs in the application of electromagnetic wave absorption.

Lignocellulosic ethanol and butanol production by Saccharomyces cerevisiae and Clostridium beijerinckii co-culture using non-detoxified corn stover hydrolysate.

Considering global economic and environmental -benefits, green renewable biofuels such as ethanol and butanol are considered as sustainable alternatives to fossil fuels. Thus, developing a co-culture strategy for ethanol and butanol production by Saccharomyces cerevisiae and Clostridium beijerinckii has emerged as a promising approach for biofuel production from lignocellulosic biomass. This study developed a co-culture of S. cerevisiae and C. beijerinckii for ethanol and butanol production from non-detoxified corn stover hydrolysate. By firstly inoculating 3 % S. cerevisiae and then 7 % C. beijerinckii with 8-10 h time intervals, the optimized co-culture process gave 24.0 g/L ABE (20.8 g/L ethanol and 2.4 g/L butanol), obtaining ABE yield and productivity of 0.421 g/g and 0.55 g/L/h. The demonstrated co-culture strategy made full use of hexose and pentose in hydrolysate and contributed to total yield and efficiency compared to conventional ethanol or ABE fermentation, indicating its great potential for developing economically feasible and sustainable bioalcohols production.

A Controlled Clinical Study of Accelerated High-Dose Theta Burst Stimulation in Patients with Obsessive-Compulsive Disorder.

Background: Obsessive-compulsive disorder (OCD) is frequently treated using a combination of counseling, drugs, and, more recently various transcranial stimulation protocols, but all require several weeks to months for clinically significant improvement, so there is a need for treatments with faster onset. This study investigated whether an accelerated high-dose theta burst stimulation (ahTBS) protocol significantly improves the efficacy of OCD compared to traditional 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the routine clinical setting. Method: Forty-five patients with OCD were randomized into two groups and treated with ahTBS or 1-Hz rTMS for 5 days. Patients were assessed at baseline at the end of treatment using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results: After 5 days of treatment, there was a significant decrease in Y-BOCS scores in both groups (p < 0.001), and the difference between the two groups was not statistically significant (group × time interaction, F = 1.90, p=0.18). There was also no statistically significant difference in other secondary outcome indicators, including depression, anxiety symptoms, and response rate. However, the ahTBS group had a greater trend in response rate. Neuropsychological testing showed no negative cognitive side effects of either treatment. Conclusion: Accelerated high-dose TBS is as safe and has comparable short-term efficacy to traditional 1-Hz rTMS for the clinical treatment of OCD. Further research is needed to explore optimal ahTBS parameters, validate the utility of this treatment modality, and identify factors predictive of rapid clinical response to guide clinical decision-making. This trial is registered with NCT05221632.

Engineering of formate dehydrogenase for improving conversion potential of carbon dioxide to formate.

Formate dehydrogenase (FDH) is a D-2-hydroxy acid dehydrogenase, which can reversibly reduce CO2 to formate and thus act as non-photosynthetic CO2 reductase. In order to increase catalytic efficiency of formate dehydrogenase for CO2 reduction, two mutants V328I/F285W and V354G/F285W were obtained of which reduction activity was about two times more than the parent CbFDHM2, and the formate production from CO2 catalyzed by mutants were 2.9 and 2.7-fold higher than that of the parent CbFDHM2. The mutants had greater potential in CO2 reduction. The optimal temperature for V328I/F285W and V354G/F285W was 55 °C, and they showed increasement of relative activity under 45 °C to 55 °C compared with parent. The optimal pH for the mutants was 9.0, and they showed excellent stability in pH 4.0-11.5. The kcat/Km values of mutants were 1.75 times higher than that of the parent. Then the molecular basis for its improvement of biochemical characteristics were preliminarily elucidated by computer-aided methods. All of these results further established a solid foundation for molecular modification of formate dehydrogenase and CO2 reduction.

Restraining Interfacial Cu2+ by using Amorphous SnO2 as Sacrificial Protection Boosts CO2 Electroreduction.

The electrochemical carbon dioxide reduction reaction (CO2 RR) to formate is of great interest in the field of electrochemical energy. Cu-based material is an appealing electrocatalyst for the CO2 RR. However, retaining Cu2+ under the high cathodic potential of CO2 RR remains a great challenge, leading to low electrocatalytic selectivity, activity, and stability. Herein, inspired by corrosion science, a sacrificial protection strategy to stabilize interfacial crystalline CuO through embedding of active amorphous SnO2 (c-CuO/a-SnO2 ) is reported, which greatly boosts the electrocatalytic sensitivity, activity, and stability for CO2 RR to formate. The as-made hybrid catalyst can achieve superior high selectivity for CO2 RR to formate with a remarkable Faradaic efficiency (FE) of 96.7%, and a superhigh current density of over 1 A cm-2 that far outperforms industrial benchmarks (FE > 90%, current density > 300 mA cm-2 ). In situ X-ray absorption spectroscopy (XAS) and X-ray diffractionexperimental and theoretical calculation results reveal that the broadened s-orbital in interfacial a-SnO2 offers the lower orbital for extra electrons than Cu2+ , which can effectively retain nearby Cu2+ , and the high active interface significantly lowers the energy barrier of the limited step (* CO2 → * HCOO) and enhances the selectivity and activity for CO2 RR to formate.

Preparation of expandable vertically aligned carbon nanotube arrays/polydimethylsiloxane membrane by a modular splicing method and its application in in situ ethanol recovery from ethanol fermentation.

Aligned carbon nanotube (CNT) arrays have been widely used in the preparation of polymer composites. CNT arrays are commonly prepared by chemical vapor deposition (CVD) in a high temperature tubular furnace, and the areas of the aligned CNT/polymer membranes prepared are relatively small (<30 cm2) due to the limitation of the inner diameter of the furnace, which limits its practical application in the field of membrane separation. Herein, the vertically aligned CNT arrays/polydimethylsiloxane (PDMS) membrane with large and expandable area was prepared by a modular splicing method for the first time, with a maximum area of 144 cm2. The addition of CNT arrays with openings at both ends significantly improved the pervaporation performance of the PDMS membrane for ethanol recovery. At 80 °C, the flux (671.6 g m-2 h-1) and separation factor (9.0) of CNT arrays/PDMS membrane were increased by 435.12% and 58.52%, respectively, compared with those of the PDMS membrane. Furthermore, the expandable area enabled the CNT arrays/PDMS membrane to couple with fed-batch fermentation for pervaporation for the first time, which increased the ethanol yield (0.47 g g-1) and productivity (2.34 g L-1 h-1) by 9.3% and 4.9% respectively compared with batch fermentation. Besides, the flux (135.47-166.79 g m-2 h-1) and separation factor (8.83-9.21) of CNT arrays/PDMS membrane remained stable in this process, indicating that this membrane has the potential to be applied in industrial bioethanol production. This work provides a new idea for the preparation of large-area aligned CNT/polymer membranes, and also opens up a new direction for the application of large-area aligned CNT/polymer membranes.

Design and optimization of the tripod flexure for a 2m lightweight mirror for space application.

In order to ensure optimal optical performance, primary mirror assembly must be impervious to environmental influences. These environmental influences include gravity, assembly error, and thermal change, under which external loads are imposed on the mirror. The external loads degrade the mirror surface accuracy and cause misalignment between mirrors. In this paper, a tripod flexure with a flexible hinge is designed to alleviate the influence of the external load on the surface accuracy of a 2 m primary mirror. This structure can effectively release the rotational freedom, provide a certain translational flexibility, and yield high axial stiffness. The axial stiffness is used to increase the frequency of the primary mirror assembly. According to the fast optimization model, the derivation of close form compliance equations is developed to characterize the flexibility, and parameter optimization is done to achieve the maximum performance. Then a finite element analysis and test are used to verify the final design. The results show that the index requirements of the 2 m primary mirror have been met.

Sensorimotor network connectivity correlates with motor improvement after repetitive transcranial magnetic stimulation in patients with Parkinson's disease.

BACKGROUND: Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) generally improves Parkinson's disease (PD) motor symptoms. However, personal responses to rTMS might be different. In this study, we explore the connectivity changes in PD patients with different responses to rTMS. METHODS: Among PD patients, 25 were treated with 10Hz-rTMS and seven were with sham rTMS over the supplementary motor area for 10 days. Resting-state functional connectivity magnetic resonance imaging (rs-fMRI) was performed in PD patients before and after rTMS stimulation. Neuropsychological scales such as Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) were collected synchronously with rs-fMRI. To explore the connectivity changes after rTMS, degree centrality was calculated. RESULTS: 13 out of 25 participants were responsive to 10Hz rTMS. Degree centrality patterns in the left sensorimotor regions are primarily responsible for the differences between responsive and non-responsive individuals. Improvement in motor symptoms was substantially related to the baseline degree centrality in the left PreCG and the left PoCG. The performance in distinguishing non-responders from responders was further validated by the ROC analysis utilizing DC characteristics. Lastly, we found that connectivity increased in left PreCG and PoCG in patients with a better response to the rTMS. CONCLUSION: Taken together, these results suggest that the sensorimotor network is involved in the motor improvement following rTMS treatment, with patients with lower sensorimotor connectivity showing a tendency for greater motor improvement to HF-rTMS.

Three cases of acute chlorfenapyr poisoning / 中华劳动卫生职业病杂志

This paper reported 3 cases of poisoning caused by chlorfenagyr. Chlorfenapyr poisoning has gradually increased in clinical practice. The early stage after poisoning is digestive tract symptoms, followed by sweating, high fever, changes in consciousness, changes in myocardial enzymology, etc. Its main mechanism of intoxication is uncoupling oxidative phosphorylation. Since there is no specific antidote after poisoning, the fatality rate of chlorfenapyr poisoning remains high. The therapeutic measures are early gastrointestinal decontamination, symptomatic and supportive treatments, and early blood purification may be an effective treatment.

Optimizing multi-domain hematologic biomarkers and clinical features for the differential diagnosis of unipolar depression and bipolar depression.

There is a lack of objective features for the differential diagnosis of unipolar and bipolar depression, especially those that are readily available in practical settings. We investigated whether clinical features of disease course, biomarkers from complete blood count, and blood biochemical markers could accurately classify unipolar and bipolar depression using machine learning methods. This retrospective study included 1160 eligible patients (918 with unipolar depression and 242 with bipolar depression). Patient data were randomly split into training (85%) and open test (15%) sets 1000 times, and the average performance was reported. XGBoost achieved the optimal open-test performance using selected biomarkers and clinical features-AUC 0.889, sensitivity 0.831, specificity 0.839, and accuracy 0.863. The importance of features for differential diagnosis was measured using SHapley Additive exPlanations (SHAP) values. The most informative features include (1) clinical features of disease duration and age of onset, (2) biochemical markers of albumin, low density lipoprotein (LDL), and potassium, and (3) complete blood count-derived biomarkers of white blood cell count (WBC), platelet-to-lymphocyte ratio (PLR), and monocytes (MONO). Overall, onset features and hematologic biomarkers appear to be reliable information that can be readily obtained in clinical settings to facilitate the differential diagnosis of unipolar and bipolar depression.

Identification of serine/threonine kinases that regulate metabolism and sporulation in Clostridium beijerinckii.

Serine/threonine protein kinases (STKs) are important for signal transduction and involved in multiple physiological processes, including cell growth, central metabolism, and sporulation in bacteria. However, the role of STKs in solventogenic clostridia remains unclear. Here, we identified and comprehensively investigated six STK candidates in Clostridium beijerinckii. These STKs were classified into four groups with distinct characteristics via analysis of genetic organizations, prediction of protein domains, and multiple sequence alignment. Cbei0566 is a member of the PrkA family with 41% identity to PrkA from Bacillus subtilis, and both Cbei0666 and Cbei0813 are two-component-like STKs. Cbei1151 and Cbei1929 belong to the Hanks family STKs and consist of a cytoplasmic catalytic domain, a transmembrane region, and extracellular sensor domains. In-frame deletion mutants of cbei0566, cbei0666, cbei1929, and cbei2661 displayed similar cell growth with wild type. Both Δcbei0666 and Δcbei2661 improved acetone-butanol-ethanol (ABE) production by 14.3% (19.2 g/L vs. 16.8 g/L), and the sporulation frequencies of Δcbei0566, Δcbei1929, and Δcbei2661 significantly decreased to 35.5%, 55.1% and 44.8%, respectively. The restored phenotypes after genetic complementation demonstrated their direct link to STKs deletion. Remarkably, overexpressing cbei0566 contributed to 41.5% more spore formation and cbei1929 overexpression enhanced ABE production from 19.3 to 24.2 g/L, along with 25% less acids. These results revealed that Cbei0566 and Cbei1929 had prominent regulatory functions. This study expands the current knowledge of the existence and functions of STKs in prokaryotes and highlights the importance of STK-mediated signaling networks in developing superior strains. KEY POINTS: • First reported serine/threonine protein kinases in solventogenic clostridia • Six STKs with distinct properties possessed diverse functions in C. beijerinckii • Cbei1929 and Cbei0566 remarkably regulated solventogenesis and sporulation.

Organizing Enzymes on Self-Assembled Protein Cages for Cascade Reactions.

Cells use self-assembled biomaterials such as lipid membranes or proteinaceous shells to coordinate thousands of reactions that simultaneously take place within crowded spaces. However, mimicking such spatial organization for synthetic applications in engineered systems remains a challenge, resulting in inferior catalytic efficiency. In this work, we show that protein cages as an ideal scaffold to organize enzymes to enhance cascade reactions both in vitro and in living cells. We demonstrate that not only enzyme-enzyme distance but also the improved Km value contribute to the enhanced reaction rate of cascade reactions. Three sequential enzymes for lycopene biosynthesis have been co-localized on the exterior of the engineered protein cages in Escherichia coli, leading to an 8.5-fold increase of lycopene production by streamlining metabolic flux towards its biosynthesis. This versatile system offers a powerful tool to achieve enzyme spatial organization for broad applications in biocatalysis.

Early Effects of Repetitive Transcranial Magnetic Stimulation Combined With Sertraline in Adolescents With First-Episode Major Depressive Disorder.

Background: Adolescence is a period of high incidence for depression. However, there is a limited treatment option for the adolescent depression. For treatment-resistant major depressive disorder, HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) appears therapeutically effective. The aim of the study is to explore the early effects of repetitive transcranial magnetic stimulation in combination with sertraline in adolescents with first-episode major depressive disorder. Methods: A total of 100 teenage patients with first-episode depression were randomly divided into the study groups. Both groups were treated with sertraline. In addition, the study group was treated with ten sessions of add-on rTMS. The control group was given sertraline only. The depressive symptom and cognitive function were assessed by the Hamilton depression rating scale 17 version (HAMD-17), Children's Depression Rating Scale-Revised (CDRS-R), Integrated visual and auditory continuous performance test (IVA-CPT), and THINC-it. Results: The number of early improvers after 2 weeks of treatment in the study group was statistically significant higher compared to the control group (95.83% vs 73.47%, χ2 = 9.277, P = 0.002). There was significant difference observed in responder rates (62.50% vs. 28.57%, χ2 = 11.262, P = 0.001) or in remission rates (31.25% vs. 6.12%, χ2 = 10.130, P = 0.001) between the two groups at 4 weeks. The score of HAMD-17 and CDRS-R in the study group were significantly lower than the control group (Fgroup = 12.91 vs 10.21, P < 0.05). Attention Quotient (listening, visual and full-scale) attention quotient of IVA-CPT in the study group were higher than those in the control group after treatment, and the differences were statistically significant(P < 0.05). The study group showed higher score in Spotter than the control group after treatment (P < 0.05). Discussion: This is the most extensive blinded, randomized clinical study to date examining the efficacy of 10-Hz add-on rTMS for first-onset adolescent depression. Our results support that add-on rTMS accelerates the efficacy of the antidepressants, improving the depressive symptoms and cold cognitive function in first-episode adolescent depression. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100048534].