Regeneration of Propriospinal Axons in Rat Transected Spinal Cord Injury through a Growth-Promoting Pathway Constructed by Schwann Cells Overexpressing GDNF.

Unsuccessful axonal regeneration in transected spinal cord injury (SCI) is mainly attributed to shortage of growth factors, inhibitory glial scar, and low intrinsic regenerating capacity of severely injured neurons. Previously, we constructed an axonal growth permissive pathway in a thoracic hemisected injury by transplantation of Schwann cells overexpressing glial-cell-derived neurotrophic factor (SCs-GDNF) into the lesion gap as well as the caudal cord and proved that this novel permissive bridge promoted the regeneration of descending propriospinal tract (dPST) axons across and beyond the lesion. In the current study, we subjected rats to complete thoracic (T11) spinal cord transections and examined whether these combinatorial treatments can support dPST axons' regeneration beyond the transected injury. The results indicated that GDNF significantly improved graft-host interface by promoting integration between SCs and astrocytes, especially the migration of reactive astrocyte into SCs-GDNF territory. The glial response in the caudal graft area has been significantly attenuated. The astrocytes inside the grafted area were morphologically characterized by elongated and slim process and bipolar orientation accompanied by dramatically reduced expression of glial fibrillary acidic protein. Tremendous dPST axons have been found to regenerate across the lesion and back to the caudal spinal cord which were otherwise difficult to see in control groups. The caudal synaptic connections were formed, and regenerated axons were remyelinated. The hindlimb locomotor function has been improved.

Areca palm velarivirus 1 infection caused disassembly of chloroplast and reduction of photosynthesis in areca palm.

The expansion of betel palm cultivation is driven by rising demand for betel nut, yet this growth is accompanied by challenges such as decreased agricultural biodiversity and the spread of infectious pathogens. Among these, Yellow Leaf Disease (YLD) emerges as a prominent threat to betel palm plantation. Areca Palm Velarivirus 1 (APV1) has been identified as a primary causative agent of YLD, precipitating leaf yellowing, stunted growth, and diminished yield. However, the precise mechanisms underlying APV1-induced damage remain elusive. Our study elucidates that APV1 infiltrates chloroplasts, instigating severe damage and consequential reductions in chlorophyll a/b and carotene levels, alongside notable declines in photosynthetic efficiency. Moreover, APV1 infection exerts broad regulatory effects on gene expression, particularly suppressing key genes implicated in chloroplast function and photosynthesis. These disruptions correlate with growth retardation, yield diminishment, and compromised nut quality. Intriguingly, the paradoxical destruction of the host's photosynthetic machinery by APV1 prompts inquiry into its evolutionary rationale, given the virus's dependence on host resources for replication and proliferation. Our findings reveal that APV1-induced leaf yellowing acts as a beacon for transmission vectors, hinting at a nuanced "host-pathogen-vector co-evolutionary" dynamic.

Quantitative EEG reactivity induced by electrical stimulation predicts good outcome in comatose patients after cardiac arrest.

BACKGROUND: EEG reactivity is a predictor for neurological outcome in comatose patients after cardiac arrest (CA); however, its application is limited by variability in stimulus types and visual assessment. We aimed to evaluate the prognostic value of the quantitative analysis of EEG reactivity induced by standardized electrical stimulation and for early prognostication in this population. METHODS: This prospective observational study recruited post-CA comatose patients in Xuanwu Hospital, Capital Medical University (Beijing, China) between January 2016 and June 2023. EEG reactivity to electrical or traditional pain stimulation was randomly performed via visual and quantitative analysis. Neurological outcome within 6 months was dichotomized as good (Cerebral Performance Categories, CPC 1-2) or poor (CPC 3-5). RESULTS: Fifty-eight post-CA comatose patients were admitted, and 52 patients were included in the final analysis, of which 19 (36.5%) had good outcomes. EEG reactivity induced with the electrical stimulation had superior performance to the traditional pain stimulation for good outcome prediction (quantitative analysis: AUC 0.932 vs. 0.849, p = 0.048). When using the electrical stimulation, the AUC of EEG reactivity to predict good outcome by visual analysis was 0.838, increasing to 0.932 by quantitative analysis (p = 0.039). Comparing to the traditional pain stimulation by visual analysis, the AUC of EEG reactivity for good prognostication by the electrical stimulation with quantitative analysis was significantly improved (0.932 vs. 0.770, p = 0.004). CONCLUSIONS: EEG reactivity induced by the standardized electrical stimulation in combination with quantitative analysis is a promising formula for post-CA comatose patients, with increased predictive accuracy.

A meta-analysis of the effects of ketamine on suicidal ideation in depression patients.

The treatment of suicidal ideation in patients with depression has been a major problem faced by psychiatric and emergency departments, and reasonable drug selection is particularly important. Ketamine has been shown to reduce suicidal ideation rapidly, but the strength of the effect is unclear and there is little evidence-based medical evidence to support this. We systematically searched all articles published on PubMed, Cochrane Library, Web of Science, CNKI and EMBASE. Stata 15 and R 4.1.3 were used for meta-analysis, and odds ratios were calculated in fixed effects or random effects models based on the heterogeneity test results. Our search resulted in 505 articles; we analyzed 14 studies, which included 1,380 participants. The 14 studies included 10 randomized controlled trial (RCT) studies and 4 single-arm studies. Our study suggests that, ketamine has a significant therapeutic effect on suicidal ideation throughout the treatment cycle. We performed network meta-analyses(NMA) and pairwise meta-analyses to compare the efficacy of ketamine in the reduction of suicidal ideation. There was a significant reduction in suicidal ideation within the first day after treatment (NMA ketamine day1 RR = 10.02, 95%CI = 4.24 to 23.68). In repeated treatment, the degree of recovery of suicidal ideation after the last dose was significantly greater than that after the first dose (RR = 0.56, 95%CI = 0.51 to 0.62). Recovery of suicidal ideation was also significantly better in the treatment end point than in the placebo group at the same time point (NMA ketamine day26 RR = 4.29, 95%CI = 1.41 to 13.08). This is the first network meta-analysis to demonstrate the role of ketamine in the alleviation of suicidal ideation. Our network meta-analysis also compared the effects of different drugs at different time points, which was not done in previous studies. This is of great reference significance for future drug research andrational drug use.

Chinese hospital staff in anxiety and depression: Not only comfort patients but also should be comforted - A nationwide cross-sectional study.

BACKGROUND: Healthcare professionals are in short supply worldwide, especially in China, which can result in increased stress in the work environment and allostatic load for Chinese hospital staff. This study aimed to investigate the prevalence of anxiety and depressive symptoms and their relationship with total stress, allostatic overload, sleep quality, and episodic memory among Chinese hospital staff. METHOD: In this cross-sectional study, self-assessments including Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire-9 (PHQ-9), PsychoSocial Index (PSI), Pittsburgh Sleeping Quality Index (PSQI), and MemTrax test were used to evaluate participants' anxiety symptoms, depressive symptoms, total stress, allostatic load/overload, sleep quality, and episodic memory. RESULTS: A total of 9433 hospital staff from 304 cities participated. Anxiety prevalence was 21.0 % (95 % confidential interval (CI) 20.2 %, 21.8 %), while the prevalence of depressive symptoms was at 21.4 % (95 % CI 20.5 %, 22.2 %). 79.8 % (95 % CI 79.0 %, 80.6 %) of the hospital staff had allostatic overload. Poor sleep quality affected 50.4 % of participants, and 32.1 % experienced poor episodic memory. LIMITATIONS: This study utilized a convenience sampling approach, relying on an online survey as its data collection method. CONCLUSIONS: Hospital staff in China are facing a stressful environment with a high prevalence of anxiety and depressive symptoms, significant allostatic overload, poor sleep quality, and compromised episodic memory. It is imperative that local management and community structures enhance their support and care for these essential workers, enabling them to manage and withstand the stresses of their professional roles effectively.

Shared Latent Membership Enables Joint Shape Abstraction and Segmentation With Deformable Superquadrics.

Part-level 3D shape representations are crucial to shape reasoning and understanding. Two key sub-tasks are: 1) shape abstraction, creating primitive-based object parts; and 2) shape segmentation, finding partition-based object parts. However, for 3D object point clouds, most advanced methods produce parts relying on task-specific priors, such as similarity metrics and primitive geometries, resulting in misleading parts that deviate from semantics. To address prior limitations, we establish a foundation for joint shape abstraction and shape segmentation as formal linear transformations within a shared latent space, encapsulating essential dual-purpose membership information linking points and object parts for mutual reinforcement. We demonstrate that the transformations are underpinned by a derivation based on k-means, Non-negative Matrix Factorization (NMF), and the attention mechanism. As a result, we introduce Latent Membership Pursuit (LMP) for joint optimization of shape abstraction and segmentation. LMP utilizes a shared latent representation of object part membership to autonomously identify common object parts in both tasks without any supervision and priors. Furthermore, we adapt deformable superquadrics (DSQs) for primitives to capture variable part-level geometric and semantic information. Experiments on benchmark datasets validate that our approach enables mutual learning of shape abstraction and segmentation, and promotes consistent interpretations of 3D object shapes across instances and even categories in a fully unsupervised manner.

Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder.

Background: Although 15 mA transcranial alternating current stimulation (tACS) has a therapeutic effect on depression, the activations of brain structures in humans accounting for this tACS configuration remain largely unknown. Aims: To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA, delivered via the forehead and the mastoid electrodes in the human brain. Methods: Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve, first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS software. Results: The electric field distributions of the sagittal, coronal and axial planes showed that the bilateral frontal lobes, bilateral temporal lobes, hippocampus, cingulate, hypothalamus, thalamus, amygdala, cerebellum and brainstem were visibly stimulated by the 15 mA tACS procedure. Conclusions: Brain-wide activation, including the cortex, subcortical structures, cerebellum and brainstem, is involved in the 15 mA tACS intervention for first-episode major depressive disorder. Our results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.

Naringenin nanoparticles targeting cyclin B1 suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition.

There is growing evidence of an elevated risk of lung cancer in patients with rheumatoid arthritis. The poor prognosis of rheumatoid arthritis-associated lung cancer and the lack of therapeutic options pose an even greater challenge to the clinical management of patients. This study aimed to identify potential molecular targets associated with the progression of rheumatoid arthritis-associated lung cancer and examine the efficacy of naringenin nanoparticles targeting cyclin B1. Mendelian randomizatio analysis revealed that rheumatoid arthritis has a positive correlation with the risk of lung cancer. Cyclin B1 was significantly upregulated in patients with rheumatoid arthritis-associated lung cancer and was significantly overexpressed in synovial tissue fibroblasts. Furthermore, the overexpression of cyclin B1 in rheumatoid arthritis fibroblast-like synoviocytes, which promotes their proliferation and fibroblast-to-myofibroblast transition, can significantly contribute to the growth and infiltration of lung cancer cells. Importantly, our prepared naringenin nanoparticles targeting cyclin B1 effectively attenuated proliferation and fibroblast-to-myofibroblast transition by blocking cells at the G2/M phase. In vivo experiments, naringenin nanoparticles targeting cyclin B1 significantly alleviated the development of collagen-induced arthritis and lung orthotopic tumors. Collectively, our results reveal that naringenin nanoparticles targeting cyclin B1 can suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition. These findings provide new insights into the treatment of rheumatoid arthritis-associated lung cancer therapy.

Clinical Interviewing: An Essential but Neglected Method of Medicine.

Clinical interviewing is the basic method to understand how a person feels and what are the presenting complaints, obtain medical history, evaluate personal attitudes and behavior related to health and disease, give the patient information about diagnosis, prognosis, and treatment, and establish a bond between patient and physician that is crucial for shared decision making and self-management. However, the value of this basic skill is threatened by time pressures and emphasis on technology. Current health care trends privilege expensive tests and procedures and tag the time devoted to interaction with the patient as lacking cost-effectiveness. Instead, the time spent to inquire about problems and life setting may actually help to avoid further testing, procedures, and referrals. Moreover, the dialogue between patient and physician is an essential instrument to increase patient's motivation to engage in healthy behavior. The aim of this paper was to provide an overview of clinical interviewing and its optimal use in relation to style, flow and hypothesis testing, clinical domains, modifications according to settings and goals, and teaching. This review points to the primacy of interviewing in the clinical process. The quality of interviewing determines the quality of data that are collected and, eventually, of assessment and treatment. Thus, interviewing deserves more attention in educational training and more space in clinical encounters than it is currently receiving.

Sleep deprivation from mid-gestation leads to impaired of motor coordination in young offspring mice with microglia activation in the cerebellar vermis.

OBJECTIVE: To investigate the effects of mid-pregnancy sleep deprivation (SD) in C57BL/6 J mice on the motor coordination of the offspring and to explore the potential mechanism of microglia activation in the cerebellar vermis of the offspring involved in the induction of impaired motor coordination development. METHODS: C57BL/6 J pregnant mice were randomly divided into the SD and control groups. SD was implemented by the multi-platform method from first day of the middle pregnancy (gestation day 8, GD8). At postnatal day 21 (PND21), we measured the development of motor behavior and collected cerebellar vermis tissues to observe the activation of microglia by H&E staining, the expression of microglia-specific markers ionized calcium-binding adaptor molecule-1 (Iba-1) and cluster of differentiation 68 (CD68) by immunohistochemical, and interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor -α (TNF-α) by real-time quantitative PCR (RT-qPCR). RESULTS: In the offspring of SD group, comparing to the control group, the total time of passage and the reverse crawl distance in the balance beam test, and the frequency of falls from the suspension cord was increased; with lower max rotational speed and shorter duration in the rotarod experiment. Further, we found that the microglia of cerebellar vermis tissues emerged an amoeba-like activation. The mean gray value of Iba-1 was lower, the density of positive cells of CD68 and the expression levels of IL-6 and TNF-α were increased. CONCLUSIONS: The motor coordination of offspring is impaired, accompanying a SD from mid-pregnancy, and the cerebellar vermis showed microglia activation and pro-inflammatory response. It suggested the adverse effects of SD from mid-gestation on the development of motor coordination through the inflammatory response in the cerebellar vermis of the offspring.

Bibliometric analysis of traditional Chinese exercises in stroke rehabilitation from 2003 to 2022 using CiteSpace.

Background: A comprehensive analysis was conducted on the relevant literature pertaining to the application of traditional Chinese exercises in stroke rehabilitation over the past 20 years. Additionally, a scientific knowledge map was created to elucidate the current research status, investigate its development process and research trends, and offer novel research perspectives for future studies. Methods: The data is sourced from the WOS Core Collection, and CiteSpace software is used to analyze the relevant literature on traditional Chinese exercises in stroke rehabilitation. The analysis began with the selection of publications, countries, institutions, highly cited authors, and co-cited references to summarize the current research status of traditional exercises in stroke rehabilitation. Second, keywords were employed to identify research hotspots, and keyword clustering time zone diagrams were chosen to track the research development process. Finally, burst keywords were employed to explore the research frontiers and trends in this field. Results: In total, 937 documents were retrieved, and the annual publication volume consistently and sustainably increased. China and the USA emerged as significant contributors. The Chinese University of Hong Kong had the highest publication count, with ADA L from the University of Sydney being a highly cited author. Initially, keywords focused on cardiac output, blood flow, pressure, and performance. Over time, the focus shifted to heart failure, muscle strength, mortality, and exercise capacity. Current trends encompass outcome, impact, virtual reality, and anxiety. Conclusion: Integrating key elements of traditional exercise approaches with the specific attributes of movement disorders during the stroke recovery phase is essential. Therefore, enhancing the stroke rehabilitation training program and exploring novel avenues for traditional exercise-based interventions are critical.

Molecular regulation of oil gland development and biosynthesis of essential oils in Citrus spp.

Secretory structures in terrestrial plants serve as reservoirs for a variety of secondary metabolites. Among these, the secretory cavity of the Rutaceae family is notable for containing essential oils with a wide range of applications. However, the molecular basis underlying secretory cavity development is unknown. Here, we reveal a molecular framework for Citrus oil gland formation. Using genetic mapping and genome editing, we demonstrated that this process requires LATE MERISTEM IDENTITY1 (LMI1), a key regulator of leaf serration. A conserved GCC box element of the LMI1 promoter recruits DORNROSCHEN-like (DRNL) for transcriptional activation. This DRNL-LMI1 cascade triggers MYC5 activation, facilitating the development of oil glands and the biosynthesis of essential oils. Our findings spotlight cis-regulatory divergence within leaf shape genes, propelling novel functional tissue formation.

Biomimetic Bouligand chiral fibers array enables strong and superelastic ceramic aerogels.

Ceramic aerogels are often used when thermal insulation materials are desired; however, they are still plagued by poor mechanical stability under thermal shock. Here, inspired by the dactyl clubs of mantis shrimp found in nature, which form by directed assembly into hierarchical, chiral and Bouligand (twisted plywood) structure exhibiting superior mechanical properties, we present a compositional and structural engineering strategy to develop strong, superelastic and fatigue resistance ceramic aerogels with chiral fibers array resembling Bouligand architecture. Benefiting from the stress dissipation, crack torsion and mechanical reinforcement of micro-/nano-scale Bouligand array, the tensile strength of these aerogels (170.38 MPa) is between one and two orders of magnitude greater than that of state-of-the-art nanofibrous aerogels. In addition, the developed aerogels feature low density and thermal conductivity, good compressive properties with rapid recovery from 80 % strain, and thermal stability up to 1200 °C, making them ideal for thermal insulation applications.

Bilateral upper limb robot-assisted rehabilitation improves upper limb motor function in stroke patients: a study based on quantitative EEG.

BACKGROUND: Upper limb dysfunction after stroke seriously affects quality of life. Bilateral training has proven helpful in recovery of upper limb motor function in these patients. However, studies evaluating the effectiveness of bilateral upper limb robot-assisted training on improving motor function and quality of life in stroke patients are lacking. Quantitative electroencephalography (EEG) is non-invasive, simple, and monitors cerebral cortical activity, which can be used to evaluate the effectiveness of interventions. In this study, EEG was used to evaluate the effect of end-drive bilateral upper extremity robot-assisted training on upper extremity functional recovery in stroke patients. METHODS: 24 stroke patients with hemiplegia were randomly divided into a conventional training (CT, n = 12) group or a bilateral upper limb robot-assisted training (BRT, n = 12) group. All patients received 60 min of routine rehabilitation treatment including rolling, transferring, sitting, standing, walking, etc., per day, 6 days a week, for three consecutive weeks. The BRT group added 30 min of bilateral upper limb robot-assisted training per day, while the CT group added 30 min of upper limb training (routine occupational therapy) per day, 6 days a week, for 3  weeks. The primary outcome index to evaluate upper limb motor function was the Fugl-Meyer functional score upper limb component (FMA-UE), with the secondary outcome of activities of daily living (ADL), assessed by the modified Barthel index (MBI) score. Quantitative EEG was used to evaluate functional brain connectivity as well as alpha and beta power current source densities of the brain. RESULTS: Significant (p < 0.05) within-group differences were found in FMA-UE and MBI scores for both groups after treatment. A between-group comparison indicated the MBI score of the BRT group was significantly different from that of the CT group, whereas the FMA-UE score was not significantly different from that of the CT group after treatment. The differences of FMA-UE and MBI scores before and after treatment in the BRT group were significantly different as compared to the CT group. In addition, beta rhythm power spectrum energy was higher in the BRT group than in the CT group after treatment. Functional connectivity in the BRT group, under alpha and beta rhythms, was significantly increased in both the bilateral frontal and limbic lobes as compared to the CT group. CONCLUSIONS: BRT outperformed CT in improving ADL in stroke patients within three months, and BRT facilitates the recovery of upper limb function by enhancing functional connectivity of the bilateral cerebral hemispheres.

Muscle-targeted nanoparticles strengthen the effects of small-molecule inhibitors in ameliorating sarcopenia.

Background: Sarcopenia is an aging-related degeneration of muscle mass and strength. Small-molecule inhibitor SW033291 has been shown to attenuate muscle atrophy. Targeted nanodrug-delivery systems can improve the efficacy of small-molecule inhibitors. Methods: The skeletal muscle cell-targeted nanoparticle was called AP@SW033291, which consisted of SW033291, modular peptide ASSLNIAGGRRRRRG and PEG-DSPE. Nanoparticles were featured with particle size, fluorescence emission spectra and targeting ability. We also investigated their effects on muscle mass and function. Results: The size of AP@SW033291 was 125.7 nm and it demonstrated targeting effects on skeletal muscle; thus, it could improve muscle mass and muscle function. Conclusion: Nanoparticle AP@SW033291 could become a potential strategy to strengthen the treatment effects of small-molecule inhibitors in sarcopenia.

EEG Biofeedback Decreases Theta and Beta Power While Increasing Alpha Power in Insomniacs: An Open-Label Study.

Insomnia, often associated with anxiety and depression, is a prevalent sleep disorder. Biofeedback (BFB) treatment can help patients gain voluntary control over physiological events such as by utilizing electroencephalography (EEG) and electromyography (EMG) power. Previous studies have rarely predicted biofeedback efficacy by measuring the changes in relative EEG power; therefore, we investigated the clinical efficacy of biofeedback for insomnia and its potential neural mechanisms. We administered biofeedback to 82 patients with insomnia, of whom 68 completed 10 sessions and 14 completed 20 sessions. The average age of the participants was 49.38 ± 12.78 years, with 26 men and 56 women. Each biofeedback session consisted of 5 min of EMG and 30 min of EEG feedback, with 2 min of data recorded before and after the session. Sessions were conducted every other day, and four scale measures were taken before the first, fifth, and tenth sessions and after the twentieth session. After 20 sessions of biofeedback treatment, scores on the Pittsburgh Sleep Quality Index (PSQI) were significantly reduced compared with those before treatment (-5.5 ± 1.43,t = -3.85, p = 0.006), and scores on the Beck Depression Inventory (BDI-II) (-7.15 ± 2.43, t = -2.94, p = 0.012) and the State-Trait Anxiety Inventory (STAI) (STAI-S: -12.36 ± 3.40, t = -3.63, p = 0.003; and STAI-T: -9.86 ± 2.38, t = -4.41, p = 0.001) were significantly lower after treatment than before treatment. Beta and theta power were significantly reduced after treatment, compared with before treatment (F = 6.25, p = 0.014; and F = 11.91, p = 0.001). Alpha power was increased after treatment, compared with before treatment, but the difference was not prominently significant (p > 0.05). EMG activity was significantly decreased after treatment, compared with before treatment (F = 2.11, p = 0.015). Our findings suggest that BFB treatment based on alpha power and prefrontal EMG relieves insomnia as well as anxiety and depression and may be associated with increased alpha power, decreased beta and theta power, and decreased EMG power.

Identification and molecular characterization of a novel member of the genus Totivirus from Areca catechu L.

In previous work, RNA-seq was applied to identify the causal agent of yellow leaf disease (YLD) in areca palm (Areca catechu L.), resulting in the identification of areca palm velarivirus 1 (APV1) associated with YLD. Additionally, RNA-seq revealed a totivirus-like virus in areca palm. This work revealed that the totivirus-like virus is prevalent in asymptomatic areca palms. Therefore, it was tentatively named "areca palm latent totivirus 1" (APLTV1). The complete genome sequence of APLTV1 was determined and found to be 4754 base pairs (bp) in length, containing two ORFs whose encoded proteins share 55% and 69% amino acid (aa) sequence identity with the capsid protein (CP) and RNA-dependent RNA polymerase (RdRp), respectively, of Bursera graveolens-associated totivirus 1 (BgAT1). Phylogenetic analysis based on alignment of the CP and RdRp sequences revealed that APLTV1 clustered with other members of the genus Totivirus, suggesting that APLTV1 represents a novel species of the genus Totivirus, family Totiviridae.

Decreased placental TLR3 is associated with hepatitis B virus vaccine responsiveness in infants born to HBsAg-positive mothers.

Background: Although hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine. Methods: One hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group. Results: The TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ2=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)]. Conclusions: Decreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.