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Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play key roles in regulating testosterone secretion and spermatogenesis in male mammals, respectively, and they maintain the fertility of male animals by binding to their corresponding receptors. We designed and prepared a recombinant LH receptor (LHR) subunit vaccine and a recombinant FSH receptor (FSHR) subunit vaccine and used male Sprague Dawley (SD) rats as a model to examine their effects on testicular development, spermatogenesis, and testosterone secretion in prepubertal and pubertal mammals. Both vaccines (LHR-DTT and FSHR-DTT) significantly decreased the serum testosterone level in prepubertal rats (p < 0.05) but had no effect on the testosterone secretion in pubertal rats; both vaccines decreased the number of cell layers in the seminiferous tubules and reduced spermatogenesis in prepubertal and pubertal rats. Subunit vaccine FSHR-DTT decreased the sperm density in the epididymis in both prepubertal and pubertal rats (p < 0.01) and lowered testicular index and sperm motility in pubertal rats (p < 0.05), whereas LHR-DTT only reduced the sperm density in the epididymis in pubertal rats (p < 0.05). These results indicate that the FSHR subunit vaccine may be a promising approach for immunocastration, but it still needs improvements in effectiveness.

Abstract Clinically, activated EGFR mutation associated chemo-drugs resistance has severely threaten NSCLC patients. Nanoparticle based small interfering RNA (siRNA) therapy representing another promising alternative by silencing specific gene while still suffered from charge associated toxicity, strong immunogenicity and poor targetability. Herein, we reported a novel EGFR-mutant NSCLC therapy relying on edible and cation-free kiwi-derived extracellular vesicles (KEVs), which showed sevenfold enhancement of safe dosage compared with widely used cationic liposomes and could be further loaded with Signal Transducer and Activator of Transcription 3 interfering RNA (siSTAT3). siSTAT3 loaded KEVs (STAT3/KEVs) could be easily endowed with EGFR targeting ability (STAT3/EKEVs) and fluorescence by surface modification with tailor-making aptamer through hydrophobic interaction. STAT3/EKEVs with a controlled size of 186 nm displayed excellent stability, high specificity and good cytotoxicity towards EGFR over-expressing and mutant PC9-GR4-AZD1 cells. Intriguingly, the systemic administration of STAT3/EKEVs significantly suppressed subcutaneous PC9-GR4-AZD1 tumor xenografts in nude mice by STAT3 mediated apoptosis. This safe and robust KEVs has emerged as the next generation of gene delivery platform for NSCLC therapy after multiple drug-resistance. Graphical Abstract

Unsupervised domain adaptation (UDA) is an emerging research topic in the field of machine learning and pattern recognition, which aims to help the learning of unlabeled target domain by transferring knowledge from the source domain. To perform UDA, a variety of methods have been proposed, most of which concentrate on the scenario of single source and the single target domain (1S1T). However, in real applications, usually single source domain with multiple target domains are involved (1SmT), which cannot be handled directly by those 1S1T models. Unfortunately, although a few related works on 1SmT UDA have been proposed, nearly none of them model the source domain knowledge and leverage the target-relatedness jointly. To overcome these shortcomings, we herein propose a more general 1SmT UDA model through transferring both the source-knowledge and target-relatedness, UDA-SKTR for short. In this way, not only the supervision knowledge from the source domain but also the potential relatedness among the target domains are simultaneously modeled for exploitation in the process of 1SmT UDA. In addition, we construct an alternating optimization algorithm to solve the variables of the proposed model with a convergence guarantee. Finally, through extensive experiments on both benchmark and real datasets, we validate the effectiveness and superiority of the proposed method.

Abstract Background N6‐methyladenosine (m6A) plays an essential role in tumorigenesis and cancer progression. Long noncoding RNAs (lncRNAs) are discovered to be important targets of m6A modification, and they play fundamental roles in diverse biological processes. However, there is still a lack of knowledge with regards to the association between m6A and lncRNAs in human tumors. Methods The relationship between lncRNAs and 21 m6A regulators was comprehensively explored, through the integration of multi‐omics data from M6A2Target, m6A‐Atlas, and TCGA (The Cancer Genome Atlas). In order to explore the potential roles of m6A‐related lncRNAs in human tumors, three applicable methods were introduced, which include the construction of ceRNA networks, drug sensitivity estimation, and survival analysis. Results A substantial number of positive correlation events across 33 cancer types were found. Moreover, cancer‐specific lncRNAs were associated with tissue specificity, and cancer‐common lncRNAs were conserved in cancer‐related biological function. In particular, the m6A‐related lncRNA FGD5‐AS1 was found to be associated with cancer treatment, through its influence on cisplatin resistance in breast cancer patients. Finally, a user‐friendly interface Lnc2m6A, which is enriched with various browsing sections resource for the exhibition of relationships and putative biogenesis between lncRNAs and m6A modifications, is offered in http://hainmu‐biobigdata.com/Lnc2m6A. Conclusions In summary, the results from this paper will provide a valuable resource that guides both mechanistic and therapeutic roles of m6A‐related lncRNAs in human tumors.

ObjectiveThis meta-analysis investigated the effect of long-term exercise training (ET) including aerobic, resistance, and multicomponent ET on the levels of inflammatory biomarkers in randomized controlled trials (RCTs) involving healthy subjects.MethodsWe searched seven databases for articles until May 1st, 2023. A random-effect meta-analysis, subgroup analysis, meta-regressions as well as trim and fill method were conducted using STATA 16.0.ResultThirty-eight studies were included in the meta-analysis, involving 2,557 healthy subjects (mean age varies from 21 to 86 years). Long-term ET induced significantly decreased in the levels of interleukin-6 (IL-6) (SMD -0.16, 95% CI -0.30 to −0.03, p = 0.017), C-reactive protein (CRP) (SMD -0.18, 95% CI -0.31 to −0.06, p = 0.005), as well as tumor necrosis factor alpha (TNFα) (SMD -0.43, 95% CI -0.62 to −0.24, p

The broad-spectrum antimicrobial activity of Elsholtzia ciliate essential oil (ECO) has been previously reported, but its effectiveness against halitosis-causing bacteria such as Fusobacterium nucleatum and Porphyromonas gingivalis is not well understood. In this study, we investigated the bacteriostatic activity of ECO against planktonic cells and biofilms of F. nucleatum and P. gingivalis, as well as its ability to inhibit bacterial metabolism and production of volatile sulfur compounds (VSCs) at sub-lethal concentrations. Our findings revealed that ECO exhibited comparable activities to chlorhexidine against these oral bacteria. Treatment with ECO significantly reduced the production of VSCs, including hydrogen sulfide, dimethyl disulfide, and methanethiol, which are major contributors to bad breath. As the major chemical components of ECO, carvacrol, p-cymene, and phellandrene, were demonstrated in vitro inhibitory effects on F. nucleatum and P. gingivalis, and their combined use showed synergistic and additive effects, suggesting that the overall activity of ECO is derived from the cumulative or synergistic effect of multiple active components. ECO was found to have a destructive effect on the bacterial cell membrane by examining the cell morphology and permeability. Furthermore, the application of ECO induced significant changes in the bacterial composition of saliva-derived biofilm, resulting in the elimination of bacterial species that contribute to halitosis, including Fusobacterium, Porphyromonas, and Prevotella. These results provide experimental evidence for the potential clinical applications of ECOs in the prevention and treatment of halitosis.

Summary: Detection of radioactive iodide ions (I–) is important for protecting human beings from the hazards of radioactive pollution. Herein, we present a protocol for detecting I– using a zirconium(IV)-enhanced strategy. We describe steps for optimizing the I– detection approach, establishing standard curves, and finally applying the approach. The use of zirconium(IV) greatly improves the detection performance and endows this approach with an ultralow detection limit of 0.176 nM together with wide applicability in various aqueous environments.For complete details on the use and execution of this protocol, please refer to Feng et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background Intestinal obstruction caused by endometriosis maybe easily misdiagnosed as a tumor or other occupying disease in emergency condition. How to deal with it depending on the clarity of the preoperative diagnosis and the experience of the surgeon. Case presentation A 47-year-old woman, admitted to our emergency service with abdominal pain and distension for 5 days, anal stop exhausting and defecating for 3 days. Based on imaging and laboratory examination, we made a preoperative diagnosis of rectal endometriosis probably. After 7 days of colon decompression with a intestinal obstruction catheter, an operation of laparoscopic partial rectal and sigmoid resection without protective stoma and total hysterectomy was performed successfully. The patient obtained a smooth postoperative course and doing well after 12-weeks follow up. Conclusions Obstruction caused by rectal endometriosis is very rare and easily overlooked by surgeon and gynecologist. Appropriate preoperative diagnosis and preoperative management can reduce the trauma and incidence of complications.

Abstract Background ClC-3 chloride channels promote osteogenic differentiation. Transforming growth factor-β1 (TGF-β1) and its receptors are closely related to ClC-3 chloride channels, and canonical TGF-β1 signaling is largely mediated by Smad proteins. The current study aimed to explore the role of the Smad2/3/4 signaling pathway in the mechanism by which ClC-3 chloride channels regulate osteogenic differentiation in osteoblasts. Methods First, real-time PCR and western blotting were used to detect the expression of Smad and mitogen-activated protein kinase (MAPK) proteins in response to ClC-3 chloride channels. Second, immunocytochemistry, coimmunoprecipitation (Co-IP) and immunofluorescence analyses were conducted to assess formation of the Smad2/3/4 complex and its translocation to the nucleus. Finally, markers of osteogenic differentiation were determined by real-time PCR, western blotting, ALP assays and Alizarin Red S staining. Results ClC-3 chloride channels knockdown led to increased expression of Smad2/3 but no significant change in p38 or Erk1/2. Furthermore, ClC-3 chloride channels knockdown resulted in increases in the formation of the Smad2/3/4 complex and its translocation to the nucleus. In contrast, the inhibition of TGF-β1 receptors decreased the expression of Smad2, Smad3, p38, and Erk1/2 and the formation of the Smad2/3/4 complex. Finally, the expression of osteogenesis-related markers were decreased upon ClC-3 and Smad2/3/4 knockdown, but the degree to which these parameters were altered was decreased upon the knockdown of ClC-3 and Smad2/3/4 together compared to independent knockdown of ClC-3 or Smad2/3/4. Conclusions The Smad2/3 proteins respond to changes in ClC-3 chloride channels. The Smad2/3/4 signaling pathway inhibits osteogenic differentiation regulation by ClC-3 chloride channels in MC3T3-E1 cells.

It is of great significance to explore the physical properties of optical propagation, thus the scholars are keen on the physical essence represented by classical mathematical physics equations. In this paper, a higher order nonlinear Schrödinger equation describing the behavior of polarization mode in optical fibers is firstly analyzed qualitatively, and the existence of periodic and soliton solutions is proved by using bifurcation method. Secondly, all chirped wave patterns with special form for the equation are obtained by using the complete discrimination system for polynomial method and direct integral method, the chirped rational functions and some elliptic functions wave patterns are initially found. As a result, the parameter stability of these patterns is given for the first time, which shows the variant of patterns as the parameters change, and the graphs of several typical patterns are drawn.

ObjectivesThis study aimed to investigate the potential mechanism of hyperoestrogensim elicited by ovulation induction affects endometrial receptivity and leads to embryo implantation abnormality or failure.Study designEstablishment of ovulation induction mouse model. Changes in mouse body weight, ovarian weight, serum E2 level and oestrous cycle were observed. During the peri-implantation period, morphological changes in the mouse uterus and implantation sites and the localization and protein levels of oestrogen receptors ERα and ERβ, the tight junction factors CLDN3 and OCLN, the aquaporins AQP3, AQP4 and AQP8, and the sodium channel proteins SCNN1α, SCNN1β and SCNN1γ were observed. The expression and cellular localization of ERα, CLDN3, AQP8 and SCNN1 β in RL95-2 cell line were also detected by western blotting and immunofluorescence.ResultsOvarian and body weights were significantly higher in the 5 IU and 10 IU groups than in the CON group. The E2 level was significantly higher in the 10 IU group than in the CON group. The mice in the 10 IU group had a disordered oestrous cycle and were in oestrus for a long time. At 5.5 dpc, significantly fewer implantation sites were observed in the 10 IU group than in the CON (p

IntroductionTraumatic brain injury (TBI) is a major public health concern in children. Children with TBI have elevated risk in developing attention deficits. Existing studies have found that structural and functional alterations in multiple brain regions were linked to TBI-related attention deficits in children. Most of these existing studies have utilized conventional parametric models for group comparisons, which have limited capacity in dealing with large-scale and high dimensional neuroimaging measures that have unknown nonlinear relationships. Nevertheless, none of these existing findings have been successfully implemented to clinical practice for guiding diagnoses and interventions of TBI-related attention problems. Machine learning techniques, especially deep learning techniques, are able to handle the multi-dimensional and nonlinear information to generate more robust predictions. Therefore, the current research proposed to construct a deep learning model, semi-supervised autoencoder, to investigate the topological alterations in both structural and functional brain networks in children with TBI and their predictive power for post-TBI attention deficits.MethodsFunctional magnetic resonance imaging data during sustained attention processing task and diffusion tensor imaging data from 110 subjects (55 children with TBI and 55 group-matched controls) were used to construct the functional and structural brain networks, respectively. A total of 60 topological properties were selected as brain features for building the model.ResultsThe model was able to differentiate children with TBI and controls with an average accuracy of 82.86%. Functional and structural nodal topological properties associated with left frontal, inferior temporal, postcentral, and medial occipitotemporal regions served as the most important brain features for accurate classification of the two subject groups. Post hoc regression-based machine learning analyses in the whole study sample showed that among these most important neuroimaging features, those associated with left postcentral area, superior frontal region, and medial occipitotemporal regions had significant value for predicting the elevated inattentive and hyperactive/impulsive symptoms.DiscussionFindings of this study suggested that deep learning techniques may have the potential to help identifying robust neurobiological markers for post-TBI attention deficits; and the left superior frontal, postcentral, and medial occipitotemporal regions may serve as reliable targets for diagnosis and interventions of TBI-related attention problems in children.

ObjectiveTo investigate the prevalence of multiple chronic conditions (MCC) and its influence on activities of daily living (ADL) among residents aged 60 years and above in Henan province and to provide evidences for improving the quality of life of the elderly. MethodsWith stratified cluster sampling, we recruited 6 014 permanent residents aged 60 years and above in 36 urban districts and 54 rural townships across Henan province; a face-to-face survey was conducted among the residents with a self-designed questionnaire on MCC and ADL during July – September, 2019. Multivariate unconditional logistic regression model was used to analyze the influence of MCC on ADL. ResultsOf the 5 570 participants with valid information, 1210 (21.72%) were identified as having MCC. Among the 1210 participants with MCC, 754 (62.31%), 242 (20.00%), and 214 (17.69%) suffered from two, three, and four or more chronic diseases, respectively. Impaired ADL was reported by 2 135 (38.33%) of the all participants; of the impaired ADL sufferers, 1 744 (81.69%), 262 (12.27%), and 129 (6.04%) had mild, moderate, and severe ADL impairment. After adjusting for potential confounding factors such as gender, age, education, marital status, residence, living conditions, monthly income per capita, and medical insurance payment mode, the results of unconditional multivariate logistic regression analysis showed that the participants with MCC, in contrast to those without MCC, were at an increased risk of ADL impairment (odds ratio [OR] = 2.484, 95% confidence interval [95% CI]: 1.800 – 3.428); the results also revealed that the MCC sufferers with 4 or more chronic diseases were more likely to have ADL impairment (OR = 1.527, 95% CI: 1.049 – 2.224) compared to the MCC sufferers with only one chronic disease and the participants without chronic disease. ConclusionThe prevalence of MCC is relatively low but MCC can increase the risk of ADL impairment among the elderly in Henan province.

Ethylene plays an important role in plant development and stress resistance. The rate-limiting enzyme in ethylene biosynthesis is 1-aminocyclopropane-1-carboxylic acid synthase (ACS). C. quinoa (Chenopodium quinoa) is an important food crop known for its strong tolerance to abiotic stresses. However, knowledge regarding the ACS gene family in C. quinoa remains restricted. In this study, we successfully identified 12 ACS genes (CqACSs) from the C. quinoa genome. Through thorough analysis of their sequences and phylogenetic relationships, it was verified that 8 out of these 12 CqACS isozymes exhibited substantial resemblance to ACS isozymes possessing ACS activity. Furthermore, these eight isozymes could be categorized into three distinct groups. The four remaining CqACS genes grouped under category IV displayed notable similarities with AtACS10 and AtACS12, known as amido transferases lacking ACS activity. The CqACS proteins bore resemblance to the AtACS proteins and had the characteristic structural features typically observed in plant ACS enzymes. Twelve CqACS genes were distributed across 8 out of the 18 chromosomes of C. quinoa. The CqACS genes were expanded from segment duplication. Many cis-regulatory elements related with various abiotic stresses, phytohormones, and light were found. The expression patterns of ACS genes varied across different tissues of C. quinoa. Furthermore, the analysis of gene expression patterns under abiotic stress showed that CqACS genes can be responsive to various stresses, implying their potential functions in adapting to various abiotic stresses. The findings from this research serve as a foundation for delving deeper into the functional roles of CqACS genes.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high prevalence, heritability, and heterogeneity. Children with a positive family history of ADHD have a heightened risk of ADHD emergence, persistence, and executive function deficits, with the neural mechanisms having been under investigated. The objective of this study was to investigate working memory-related functional brain activation patterns in children with ADHD (with vs. without positive family histories (ADHD-F vs. ADHD-NF)) and matched typically developing children (TDC). Voxel-based and region of interest analyses were conducted on two-back task-based fMRI data of 362 subjects, including 186, 96, and 80 children in groups of TDC, ADHD-NF, and ADHD-F, respectively. Relative to TDC, both ADHD groups had significantly reduced activation in the left inferior frontal gyrus (IFG). And the ADHD-F group demonstrated a significant positive association of left IFG activation with task reaction time, a negative association of the right IFG with ADHD symptomatology, and a negative association of the IFG activation laterality index with the inattention symptom score. These results suggest that working memory-related functional alterations in bilateral IFGs may play distinct roles in ADHD-F, with the functional underdevelopment of the left IFG significantly informing the onset of ADHD symptoms. Our findings have the potential to assist in tailored diagnoses and targeted interventions in children with ADHD-F.

Firstly, GO was modified by isophorone diisocyanate (IPDI). GO was successfully grafted with isocyanate (-NCO) by FTIR. Then, in-situ polymerization was used to react polytetramethylene ether glycol 1000 (PTMG 1000) with —NCO on modified GO (IGO), and then prepolymerized with diphenylmethylene diisocyanate (MDI) to prepare IGO @ thermoplastic polyurethane elastomer (TPU) nanocomposites. As a comparison, GO was added during the pre polymerization of MDI and PTMG 1000, and GO/TPU composite materials were prepared by solution blending method. The results indicated that, compared to GO/TPU and pure TPU, IGO@TPU had better mechanical properties. The tensile strength and elongation at break of IGO@TPU were 36 MPa and 570.5% respectively, which increased by 338% and 70.6% compared with TPU and 188% and 61.5% compared with GO/TPU.

Secondary electron emission (SEE) is a fundamental phenomenon of particle/surface interaction, and the multipactor effect induced by SEE can result in disastrous impacts on the performance of microwave devices. To suppress the SEE-induced multipactor, an Ni (111) surface covered with a monolayer of graphene was proposed and studied theoretically via the density functional theory (DFT) method. The calculation results indicated that redistribution of the electron density at the graphene/Ni (111) interface led to variations in the work function and the probability of SEE. To validate the theoretical results, experiments were performed to analyze secondary electron yield (SEY). The measurements showed a significant decrease in the SEY on an Ni (111) surface covered with a monolayer of graphene, accompanied by a decrease in the work function, which is consistent with the statistical evidence of a strong correlation between the work function and SEY of metals. A discussion was given on explaining the experimental phenomenon using theoretical calculation results, where the empty orbitals lead to an electron trapping effect, thereby reducing SEY.

Abstract Background Dietary fiber (DF) is often eschewed in swine diet due to its anti-nutritional effects, but DF is attracting growing attention for its reproductive benefits. The objective of this study was to investigate the effects of DF intake level on oocyte maturation and uterine development, to determine the optimal DF intake for gilts, and gain microbial and metabolomic insight into the underlying mechanisms involved. Methods Seventy-six Landrace × Yorkshire (LY) crossbred replacement gilts of similar age (92.6 ± 0.6 d; mean ± standard deviation [SD]) and body weight (BW, 33.8 ± 3.9 kg; mean ± SD) were randomly allocated to 4 dietary treatment groups (n = 19); a basal diet without extra DF intake (DF 1.0), and 3 dietary groups ingesting an extra 50% (DF 1.5), 75% (DF 1.75), and 100% (DF 2.0) dietary fiber mixture consisting of inulin and cellulose (1:4). Oocyte maturation and uterine development were assessed on 19 d of the 2nd oestrous cycle. Microbial diversity of faecal samples was analysed by high-throughput pyrosequencing (16S rRNA) and blood samples were subjected to untargeted metabolomics. Results The rates of oocytes showing first polar bodies after in vitro maturation for 44 h and uterine development increased linearly with increasing DF intake; DF 1.75 gilts had a 19.8% faster oocyte maturation rate and a 48.9 cm longer uterus than DF 1.0 gilts (P 0.1%) increased linearly or quadratically with increasing DF intake. Untargeted metabolic analysis revealed significant changes in serum metabolites that were closely associated with microbiota, including serotonin, a gut-derived signal that stimulates oocyte maturation. Conclusions The findings provide evidence of the benefits of increased DF intake by supplementing inulin and cellulose on oocyte maturation and uterine development in gilts, and new microbial and metabolomic insight into the mechanisms mediating the effects of DF on reproductive performance of replacement gilts.

Objective: Phlegm-stasis syndrome is one of the most common traditional Chinese medicine (TCM) syndromes and found in 59% of patients with coronary heart disease (CHD) in routine TCM clinical practice in China. One of the diagnostic criteria of phlegm-stasis syndrome is its characteristic white-greasy and thin tongue coating. We have previously reported that different types of tongue coating have different microbiome characteristics that can be used as diagnostic markers. However, the microbial characteristics of tongue coating of CHD patients with phlegm-stasis syndrome, including coating feature and underlying reason of formation, have rarely been reported. Herein, we examined the characteristic microbiome of tongue coating, and discussed the cause of tongue coating formation via salivary proteins in patients with phlegm-stasis syndrome. Methods: We examined white-greasy and thin tongue coatings obtained from 10 patients with CHD having phlegm-stasis syndrome (n = 10), and compared with those of patients with almost no coating – patients with Qi-Yin deficiency syndrome (n = 10) – and healthy controls (n = 10). 16S rRNA sequencing of tongue coating microbiome and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative analysis of salivary proteins were used to detect tongue coating and salivary protein separately. Salivary levels of sIgA, lysozyme, and amylase were detected by ELISA. Results: We identified Candidatus_Saccharimonas and Candidate_division_TM7_norank as the prominent members of tongue coating in patients with CHD having phlegm-stasis syndrome. Salivary proteins involved in biological processes, pentose phosphate pathway, and complement and coagulation cascades were among the differentially expressed proteins identified in patients with CHD having phlegm-stasis syndrome on iTRAQ analysis. Moreover, the formation of microbiota in tongue coating was associated with salivary sIgA, lysozyme, and saliva flow rate. Conclusions: We explored the characteristics of microbial composition of tongue coating patients with CHD having phlegm-stasis syndrome and identified correlations between salivary proteins and microbiome formation, providing a theoretical and mechanistic basis for tongue coating formation.

Chromatin regulators (CRs) regulate the gene transcription process through combinatorial patterns, which currently remain obscure for pan-cancer. This study identified the interaction of CRs and constructed CR-CR interaction networks across five tumor cell lines. The global interaction analysis revealed that CRs tend to function in synergistically. In addition, common and specific CRs in interaction networks were identified, and the epigenetic processes of these CRs in regulating gene transcription were analyzed. Common CRs have conserved binding sites but cooperate with different partners in multiple tumor cell lines. They also participate in gene transcription regulation, through mediation of different histone modifications (HMs). Specific CRs, ATF2 and PRDM10 were found to distinguish liver cancer samples with different prognosis. PRDM10 participates in gene transcription regulation, by exertion of influence on the DNA methylation level of liver cancer. Through analysis of the edges in the CR-CR interaction networks, it was found EP300-TAF1 has genome-wide distinct signaling patterns, which exhibit different effects on downstream targets. This analysis provides novel insights for the understanding of synergistic mechanism of CRs function, as controllers of gene transcription across cancer types.

The repetitive transcranial magnetic stimulation (rTMS) shows great potential in the treatment of Alzheimer’s disease (AD). However, its treatment efficacy for AD patients in moderate to severe stage is relatively evaluated. Here, we proposed a randomized, sham-controlled, clinical trial of rTMS among 35 moderate-to-severe AD patients. A high frequency (10 Hz) stimulation of the left dorsal lateral prefrontal cortex (DLPFC), 60-session long treatment lasting for 3 months procedure was adopted in the trial. Each participant completed a battery of neuropsychological tests at baseline and post-treatment for evaluation of the rTMS therapeutic effect. Twelve of them completed baseline resting-state functional magnetic resonance imaging (fMRI) for exploration of the underlying neural contribution to individual difference in treatment outcomes. The result showed that the rTMS treatment significantly improved cognitive performance on the severe impairment battery (SIB), reduced psychiatric symptoms on the neuropsychiatric inventory (NPI), and improved the clinician’s global impression of change (CIBIC-Plus). Furthermore, the result preliminarily proposed resting-state multivariate functional connectivity in the (para) hippocampal region as well as two clusters in the frontal and occipital cortices as a pre-treatment neuroimaging marker for predicting individual differences in treatment outcomes. The finding could brought some enlightenment and reference for the rTMS treatment of moderate and severe AD patients.