tRNA modification profiling reveals epitranscriptome regulatory networks in Pseudomonas aeruginosa.

Transfer RNA (tRNA) modifications have emerged as critical posttranscriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications - the tRNA epitranscriptome - very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to a Pseudomonas aeruginosa transposon insertion mutant library comprising 5,746 strains. Analysis of >200,000 tRNA modification data points validated the annotations of predicted tRNA modification genes, uncovered novel tRNA-modifying enzymes, and revealed tRNA modification regulatory networks in P. aeruginosa. Platform adaptation for RNA-seq library preparation would complement epitranscriptome studies, while application to human cell and mouse tissue demonstrates its utility for biomarker and drug discovery and development.

In silico off-target profiling for enhanced drug safety assessment.

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.

[Imaging findings in 12 cases of Warthin-like mucoepidermoid carcinoma].

PURPOSE: To summarize the ultrasound, CT and MRI manifestations of Warthin-like mucoepidermoid carcinoma (WT-MEC), and to explore its imaging characteristics, so as to provide reference for clinical and preoperative diagnosis. METHODS: The clinical information and imaging data of ultrasound, CT and MRI of 12 patients with WT-MEC diagnosed by pathology in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were collected, and their specific characteristics were retrospectively summarized. RESULTS: Among the 12 WT-MEC patients, there were 7 males and 5 females, with an average age of (42.7±16) years. Seven cases underwent ultrasound examination, 6 cases underwent CT examination, and 2 cases underwent MRI examination. Radiologically, all the lesions presented as a solitary mass. 11/12 lesions(91.7%) were identified as well-defined margins, and 10/12(83.3%) as solid-cystic masses. All solid-cystic lesions contained multiple cystic areas with variable sizes. On US images, most lesions showed mixed-echoic echogenicity(5/7, 71.4%), poor vascularization (6/7, 85.7%) and acoustic enhancement (6/7, 85.7%). CT revealed all the lesions (6/6, 100%) as a soft-tissue mass with heterogeneous enhancement (5/6, 83.3%). MRI imaging demonstrated the neoplasm with low or iso-signal intensity on plain T1WI and hyperintensity on T2WI. The heterogeneous enhancement was shown on contrast-enhanced T1WI. CONCLUSIONS: Most WT-MECs represent as a solitary, well-defined, solid-cystic mass in the parotid gland. The neoplasm may be characterized by the multiple and variable-sized cystic components within the tumor.

Association between different obesity patterns and the risk of NAFLD detected by transient elastography: a cross-sectional study.

BACKGROUND: Obesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US. METHODS: Data from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m2 and above. General obesity was identified with a BMI of 28.0 kg/m2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations. RESULTS: A total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74-12.70], 2.84 [2.38-3.39], 3.02 [2.02-4.51], and 9.53 [7.79-11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42-1.53; P < 0.001). WC also demonstrated strong discriminatory ability for NAFLD in Receiver Operating Characteristic (ROC) analysis, achieving an Area Under the Curve (AUC) of 0.802. CONCLUSIONS: Different patterns of obesity are risk factors for NAFLD. An increase in WC significantly increased NAFLD risk. More attention should be paid to preventing different patterns of obesity among adults.

Fabrication of multifunctional cotton fabrics with quaternized N-halamine endowing the synergetic rechargeable antibacterial, wound healing and self-cleaning performances.

Cotton has attracted considerable attention due to its functional characteristics. The focus of research on cotton has shifted in recent years towards designing multi-functional and modified media for cotton fibers, which can be firmly combined with textiles, giving them reusability and extending their service life. This study constructed a synergistic antibacterial layer of quaternary ammonium compounds (QACs) and N-halamine (Hals) using an in-situ free radical copolymerization method in water, named QACs/Hals@cotton-Cl. The route significantly increases the number of antibacterial active centers. FTIR, XPS, and SEM were used to systematically analyze the product's chemical structure, surface morphology, and other characteristics. The modified fabric's antibacterial efficiency, wound healing, renewability, and durability were also evaluated. The chlorinated modified cotton fabric could completely eradicate S. aureus and E. coli within 10 min. Compared with pure cotton, it notably promoted the healing rate of infected wounds in mice. The modification method imparted excellent hydrophobicity to the cotton fabric, with a contact angle exceeding 130°, making it easy to remove surface stains. After 30 days of regular storage and 24 h of UV irradiation, the active chlorine concentration (Cl+%) only decreased by 25 % and 39 %, respectively, and the reduced Cl+% was effectively recharged via simple re-chlorination. The hydrophobicity and antimicrobial properties of QACs/Hals@cotton-Cl remained stable even after 20 cycles of friction. This simple synthesis technique provides a convenient approach for the scalable fabrication of multifunctional and rechargeable antibacterial textiles, with potential applications in medical devices and personal hygiene protection.

The functional connectivity between right insula and anterior cingulate cortex underlying the association between future self-continuity and delay discounting.

Delay discounting refers to the tendency of individuals to devalue future rewards as the delay in their receipt increases over time. Previous studies have indicated that future self-continuity correlates with delay discounting rates. However, the neural basis underlying the relationship between future self-continuity and delay discounting is not clear. To address this question, we used voxel-based morphometry and resting-state functional connectivity analyses to investigate the neural basis underlying the association between future self-continuity and delay discounting. Behavioral result showed that future self-continuity was positively associated with delay discounting. Voxel-based morphometry analysis result indicated that gray matter volume in the right dorsal anterior insula was positively correlated with future self-continuity. Resting-state functional connectivity analysis found that functional connectivity between the right dorsal anterior insula and anterior cingulate cortex was positively associated with future self-continuity. Mediation analysis showed that the right dorsal anterior insula-right anterior cingulate cortex functional connectivity partially mediated the relationship between future self-continuity and delay discounting. These results suggested that right dorsal anterior insula-right anterior cingulate cortex functional connectivity could be the neural basis underlying the association between future self-continuity and delay discounting. In summary, the study provided novel insights into how future self-continuity affected delay discounting and offers new explanations from a neural perspective.

Research trends in lipid-lowering therapies for coronary heart disease combined with hyperlipidemia: a bibliometric study and visual analysis.

Background: Cardiovascular disease (CVD) poses a significant global health and economic challenge, with atherosclerosis being a primary cause. Over the past 40 years, substantial research has been conducted into the prevention and reversal of atherosclerosis, resulting in the development of lipid-lowering agents such as statins and fibrates. Despite the extensive literature and formulation of numerous therapeutic guidelines in this domain, a comprehensive bibliometric analysis of the current research landscape and trends has not been performed. This study aimed to elucidate the evolution and milestones of research into lipid-lowering treatments for coronary heart disease (CHD) in conjunction with hyperlipidemia through bibliometric analysis, offering insights into future directions for treatment strategies. Methods: This study examined publications from 1986 to 2023 retrieved from the Web of Science database (Core Collection). Utilizing tools such as VOSviewer, Pajek, and CiteSpace, we analyzed publication and citation numbers, H-indexes, contributions by countries and institutions, authorship, journal sources, and keyword usage to uncover research trajectories and areas of focus. Results: Our analysis of 587 publications revealed a recent surge in research output, particularly post-2003. The American Journal of Cardiology published the highest number of studies, with 40 articles, whereas Circulation received the highest number of citations (6,266). Key contributors included the United States, Japan, and China, with the United States leading in citation numbers and the H-index. Harvard University and Leiden University emerged as pivotal institutions, and Professors J. Wouter Jukema and Robert P. Giugliano were identified as leading experts. Keyword analysis disclosed five thematic clusters, indicating a shift in research towards new drug combinations and strategies, signaling future research directions. Conclusion: The last 4 decades have seen a notable rise in publications on lipid-lowering therapies for CHD and hyperlipidemia, with the United States retaining world-leading status. The increase in international collaboration aids the shift towards research into innovative lipid-lowering agents and therapeutic approaches. PCSK9 inhibitors and innovative combination therapies, including antisense oligonucleotides and angiopoietin-like protein 3 inhibitors, provide avenues for future research, intending to maximize the safety and efficacy of treatment approaches.

Linewidth Measurement of a Narrow-Linewidth Laser: Principles, Methods, and Systems.

Narrow-linewidth lasers mainly depend on the development of advanced laser linewidth measurement methods for related technological progress as key devices in satellite laser communications, precision measurements, ultra-high-speed optical communications, and other fields. This manuscript provides a theoretical analysis of linewidth characterization methods based on the beat frequency power spectrum and laser phase noise calculations, and elaborates on existing research of measurement technologies. In addition, to address the technical challenges of complex measurement systems that commonly rely on long optical fibers and significant phase noise jitter in the existing research, a short-delay self-heterodyne method based on coherent envelope spectrum demodulation was discussed in depth to reduce the phase jitter caused by 1/f noise. We assessed the performance parameters and testing conditions of different lasers, as well as the corresponding linewidth characterization methods, and analyzed the measurement accuracy and error sources of various methods.

Temperature dependence of the rain-gas and snow-gas partition coefficients for nearly a thousand chemicals.

Compared to the particle-gas partition coefficients (KPG), the rain-gas (KRG) and snow-gas (KSG) partition coefficients are also essential in studying the environmental behavior and fate of chemicals in the atmosphere. While the temperature dependence for the KPG have been extensively studied, the study for KRG and KSG are still lacking. Adsorption coefficients between water surface-air (KIA) and snow surface-air (KJA), as well as partition coefficients between water-air (KWA) and octanol-air (KOA) are vital in calculating KRG and KSG. These four basic adsorption and partition coefficients are also temperature-dependent, given by the well-known two-parameters Antoine equation logKXY = AXY + BXY/T, where KXY is the adsorption or partition coefficients, AXY and BXY are Antoine parameters (XY stand for IA, JA, WA, and OA), and T is the temperature in Kelvin. In this study, the parameters AXY and BXY are calculated for 943 chemicals, and logKXY can be estimated at any ambient temperature for these chemicals using these Antoine parameters. The results are evaluated by comparing these data with published experimental and modeled data, and the results show reasonable accuracy. Based on these coefficients, temperature-dependence of logKRG and logKSG is studied. It is found that both logKRG and logKSG are linearly related to 1/T, and Antoine parameters for logKRG and logKSG are also estimated. Distributions of the 943 chemicals in the atmospheric phases (gas, particle, and rain/snow), are illustrated in a Chemical Space Map. The findings reveal that, at environmental temperatures and precipitation days, the dominant state for the majority of chemicals is the gaseous phase. All the AXY and BXY values for logKSG, logKRG, and basic adsorption and partition coefficients, both modeled by this study and collected from published work, are systematically organized into an accessible dataset for public utilization.

A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy.

Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.

Effectiveness of repetitive transcranial magnetic stimulation for insomnia disorder on fear memory extinction: study protocol for a randomised controlled trial.

BACKGROUND: Fear memory extinction is closely related to insomnia. Repetitive transcranial magnetic stimulation (rTMS) is safe and effective for treating insomnia disorder (ID), and it has been shown to be an efficient method for modulating fear extinction. However, whether rTMS can improve fear extinction memory in ID patients remains to be studied. In this study, we specifically aim to (1) show that 1 Hz rTMS stimulation could improve fear extinction memory in ID patients and (2) examine whether changes in sleep mediate this impact. METHODS AND DESIGN: We propose a parallel group randomised controlled trial of 62 ID participants who meet the inclusion criteria. Participants will be assigned to a real rTMS group or a sham rTMS group. The allocation ratio will be 1:1, with 31 subjects in each group. Interventions will be administered five times per week over a 4-week period. The assessments will take place at baseline (week 0), post-intervention (week 4), and 8-week follow-up (week 8). The primary outcome measure of this study will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) scores from baseline to post-intervention at week 4. The secondary outcome measures include the mean change in skin conductance response (SCR), fear expectation during fear extinction, Insomnia Severity Index (ISI), Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). DISCUSSION: This study will be the first examination of the impact of rTMS on fear memory extinction in ID patients. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2300076097. Registered on 25 September 2021.

Analysis of the nursing effects of integrated medical and nursing care intervention in correction surgery for children with concealed penis.

OBJECTIVE: This study aimed to analyze and explore the nursing effects of integrated medical and nursing care intervention in correction surgery for children with concealed penis. METHODS: A total of 76 eligible patients with concealed penis were randomly divided into an observation group and a control group. The control group received conventional nursing care, while the observation group received integrated medical and nursing care intervention. Outcomes include pain levels, comfort status, incidence of complications, and nursing satisfaction were collected and analyzed to investigate the nursing effects of the integrated medical and nursing care model. RESULTS: After 2/3 days of nursing intervention, the patients in the observation group had significantly lower pain scores (measured by FPS-R) compared to the control group (P < 0.05). The patients in the observation group also had significantly higher comfort scores (measured by Kolcabal) compared to the control group (P < 0.05). The incidence of complications in the observation group was significantly lower than that in the control group (2.63 vs. 23.68, P < 0.05). Parental satisfaction in the observation group was significantly higher than that in the control group (P < 0.05). CONCLUSION: The integrated medical and nursing care intervention in correction surgery for children with concealed penis demonstrated positive nursing effects. It effectively reduced pain, improved comfort, lowered the risk of complications, and increased parental satisfaction. This approach maximizes the role of nursing care and is recommended for clinical implementation.

RcOST1L phosphorylates RcPIF4 for proteasomal degradation to promote flowering in rose.

Flowering is a vital agronomic trait that determines the economic value of most ornamental plants. The flowering time of rose (Rosa spp.) is photoperiod insensitive and is thought to be tightly controlled by light intensity, although the detailed molecular mechanism remains unclear. Here, we showed that rose plants flower later under low-light (LL) intensity than under high-light (HL) intensity, which is mainly related to the stability of PHYTOCHROME-INTERACTING FACTORs (RcPIFs) mediated by OPEN STOMATA 1-Like (RcOST1L) under different light intensity regimes. We determined that HL conditions trigger the rapid phosphorylation of RcPIFs before their degradation. A yeast two-hybrid screen identified the kinase RcOST1L as interacting with RcPIF4. Moreover, RcOST1L positively regulated rose flowering and directly phosphorylated RcPIF4 on serine 198 to promote its degradation under HL conditions. Additionally, phytochrome B (RcphyB) enhanced RcOST1L-mediated phosphorylation of RcPIF4 via interacting with the active phyB-binding motif. RcphyB was activated upon HL and recruited RcOST1L to facilitate its nuclear accumulation, in turn leading to decreased stability of RcPIF4 and flowering acceleration. Our findings illustrate how RcPIF abundance safeguards proper rose flowering under different light intensities, thus uncovering the essential role of RcOST1L in the RcphyB-RcPIF4 module in flowering.

A biocompatible pea protein isolate-derived bioink for 3D bioprinting and tissue engineering.

Three-dimensional bioprinting is a potent biofabrication technique in tissue engineering but is limited by inadequate bioink availability. Plant-derived proteins are increasingly recognized as highly promising yet underutilized materials for biomedical product development and hold potential for use in bioink formulations. Herein, we report the development of a biocompatible plant protein bioink from pea protein isolate. Through pH shifting, ethanol precipitation, and lyophilization, the pea protein isolate (PPI) transformed from an insoluble to a soluble form. Next, it was modified with glycidyl methacrylate to obtain methacrylate-modified PPI (PPIGMA), which is photocurable and was used as the precursor of bioink. The mechanical and microstructural studies of the hydrogel containing 16% PPIGMA revealed a suitable compress modulus and a porous network with a pore size over 100 µm, which can facilitate nutrient and waste transportation. The PPIGMA bioink exhibited good 3D bioprinting performance in creating complex patterns and good biocompatibility as plenty of viable cells were observed in the printed samples after 3 days of incubation in the cell culture medium. No immunogenicity of the PPIGMA bioink was identified as no inflammation was observed for 4 weeks after implantation in Sprague Dawley rats. Compared with methacrylate-modified gelatin, the PPIGMA bioink significantly enhanced cartilage regeneration in vitro and in vivo, suggesting that it can be used in tissue engineering applications. In summary, the PPIGMA bioink can be potentially used for tissue engineering applications.

High-Efficiency Frequency Doubling Blue-Laser VECSEL Based on Intracavity Beam Control.

Blue lasers are integral to a variety of applications, including marine communication, underwater resource exploration, cold laser processing, laser medicine, and beyond. Vertical external cavity surface-emitting lasers (VECSELs) have the advantages of high output power and tunable wavelength, and can output blue laser via frequency doubling. In this article, a new type of intracavity beam control external-cavity structure is introduced. The laser beam waist is effectively adjusted by intracavity beam control, and the frequency conversion efficiency is improved. A laser cavity stability analysis model was developed to investigate the impact of laser cavity lens parameters and relative positions on stability. The external resonant cavity of VECSELs utilizes two optical lenses to position the beam waist near the laser output coupling mirror and locates the frequency doubling crystal at a high optical power density position to optimize frequency conversion efficiency. The VECSEL straight external-cavity structure achieves a frequency conversion efficiency of up to 60.2% at 488 nm, yielding a blue laser output exceeding 1.3 W. The full width at half maximum of the 488 nm spectrum measures approximately 0.23 nm. This intracavity beam-controlled direct external-cavity structure effectively mitigates laser mode leakage and shows potential for the development of an efficient and compact blue laser source.

Comparative Study on Enzymatic Characteristics of Two κ-Carrageenases from Carrageenan-Degrading Bacterium Catenovulum agarivorans DS2.

κ-Carrageenase plays an important role in achieving the high-value utilization of carrageenan. Factors such as the reaction temperature, thermal stability, catalytic efficiency, and product composition are key considerations for its large-scale application. Previous studies have shown that the C-terminal noncatalytic domains (nonCDs) could influence the enzymatic properties, of κ-carrageenases, providing a strategy for exploring κ-carrageenases with different properties, especially catalytic products. Accordingly, two κ-carrageenases (CaKC16A and CaKC16B), from the Catenovulum agarivorans DS2, were selected and further characterized. Bioinformatics analysis suggested that CaKC16A contained a nonCD but CaKC16B did not. CaKC16A exhibited better enzymatic properties than CaKC16B, including thermal stability, substrate affinity, and catalytic efficiency. After truncation of the nonCD of CaKC16A, its thermal stability, substrate affinity, and catalytic efficiency have significantly decreased, indicating the vital role of nonCD in maintaining a good enzymatic property. Moreover, CaKC16A degraded κ-carrageenan to produce a highly single κ-neocarratetrose, while CaKC16B produced a single κ-neocarrabiose. CaKC16A could degrade ß/κ-carrageenan to produce a highly single desulfated κ-neocarrahexaose, while CaKC16B produced κ-neocarrabiose and desulfated κ-neocarratetrose. Furthermore, it was proposed that CaKC16A and CaKC16B participate in the B/KC metabolic pathway and serve different roles, providing new insight into obtaining κ-carrageenases with different properties.

Cell-free Nucleic Acid as Promising Diagnostic Biomarkers for Gastric Cancer: a Systematic Review.

Background: Gastric cancer (GC) is a common malignancy with early detection being crucial for survival. Liquid biopsy analysis using cell-free nucleic acid is a preferred method for detection. Hence, we conducted a systematic review to assess the diagnostic efficacy of cell-free nucleic acid markers for GC. Methods: We searched PubMed and ISI Web of Science databases for articles that conformed to our inclusion and exclusion criteria from 2012 to 2022. The following information was abstracted: first author, year of publication, country/region, age, male proportion, tumor stage for cases, specimen type, measurement method, targeted markers and diagnostic related indicators (including sensitivity, specificity, AUC, P-value). Results: Fifty-eight studies examined cell-free RNAs (cfRNAs) with a total of 62 individual circulating markers and 7 panels in serum or plasma, while 21 studies evaluated cell-free DNAs (cfDNAs) with 29 individual circulating markers and 7 panels. For individual cfRNAs, the median (range) sensitivity and specificity were 80% (21% - 98%) and 80% (54% - 99%), respectively. The median (range) sensitivity and specificity for cfRNA panels were 86% (83% - 90%) and 75% (60% - 98%), respectively. In comparison, the median (range) sensitivity and specificity reported for individual cfDNAs were 50% (18% - 96%) and 93% (57% - 100%), respectively, while cfDNA panels had a median (range) sensitivity and specificity of 85% (41% - 92%) and 73.5% (38% - 90%), respectively. The meta results indicate that cfRNA markers exhibit high sensitivity (80%) and low specificity (80%) for detecting GC, while cfDNA markers have lower sensitivity (59%) but higher specificity (92%). Conclusions: This review has demonstrated that cell-free nucleic acids have the potential to serve as useful diagnostic markers for GC. Given that both cfRNA and cfDNA markers have shown promising diagnostic performance for GC, the combination of the two may potentially enhance diagnostic efficiency.

High-definition transcranial direct current stimulation (HD-tDCS) in major depressive disorder with anxious distress-a study protocol for a double-blinded randomized sham-controlled trial.

BACKGROUND: Comorbid anxiety disorders and anxious distress are highly prevalent among individuals with major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. Few studies have evaluated the therapeutic effects of High-definition transcranial direct current stimulation (HD-tDCS) on depressive and anxiety symptoms among MDD patients with ADS. The current randomized controlled trial aims to assess the efficacy of HD-tDCS as an augmentation therapy with antidepressants compared to sham-control in subjects of MDD with ADS. METHODS: MDD patients with ADS will be recruited and randomly assigned to the active HD-tDCS or sham HD-tDCS group. In both groups, patients will receive the active or sham intervention in addition to their pre-existing antidepressant therapy, for 2 weeks with 5 sessions per week, each lasting 30 min. The primary outcome measures will be the change of depressive symptoms, clinical response, and the remission rate as measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before and after the intervention and at the 2nd and 6th week after the completed intervention. Secondary outcome measures include anxiety symptoms, cognitive symptoms, disability assessment, and adverse effects. DISCUSSION: The HD-tDCS applied in this trial may have treatment effects on MDD with ADS and have minimal side effects. TRIAL REGISTRATION: The trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2300071726. Registered 23 May 2023.