A telomere-to-telomere gap-free reference genome assembly of avocado provides useful resources for identifying genes related to fatty acid biosynthesis and disease resistance.

Avocado (Persea americana Mill.) is an economically valuable plant because of the high fatty acid content and unique flavor of its fruits. Its fatty acid content, especially the relatively high unsaturated fatty acid content, provides significant health benefits. We herein present a telomere-to-telomere gapless genome assembly (841.6 Mb) of West Indian avocado. The genome contains 40 629 predicted protein-coding genes. Repeat sequences account for 57.9% of the genome. Notably, all telomeres, centromeres, and a nucleolar organizing region are included in this genome. Fragments from these three regions were observed via fluorescence in situ hybridization. We identified 376 potential disease resistance-related nucleotide-binding leucine-rich repeat genes. These genes, which are typically clustered on chromosomes, may be derived from gene duplication events. Five NLR genes (Pa11g0262, Pa02g4855, Pa07g3139, Pa07g0383, and Pa02g3196) were highly expressed in leaves, stems, and fruits, indicating they may be involved in avocado disease responses in multiple tissues. We also identified 128 genes associated with fatty acid biosynthesis and analyzed their expression patterns in leaves, stems, and fruits. Pa02g0113, which encodes one of 11 stearoyl-acyl carrier protein desaturases mediating C18 unsaturated fatty acid synthesis, was more highly expressed in the leaves than in the stems and fruits. These findings provide valuable insights that enhance our understanding of fatty acid biosynthesis in avocado.

The chromosome-level genome assembly of Cananga odorata provides insights into its evolution and terpenoid biosynthesis.

Cananga odorata is known as a natural perfume tree of the Annonaceae family in Magnoliales. However, its phylogenetic position and the molecular mechanisms involved in the biosynthesis of the floral volatile organic compounds (VOCs) remain unclear. Here, by combining a variety of sequencing platforms, we present a telomere-to-telomere (T2T) genome of C. odorata with 735.83 Mb, which represents the highest integrity and assembly quality of genome in magnoliid plants reported to date. Phylogenetic analysis based on multiple datasets and approaches showed that C. odorata, as a member of magnoliids, is sister to eudicots, after their divergence from monocots. Metabolomic of VOCs in the essential oil and flowers scent showed that sesquiterpenes, especially ß-caryophyllene, were the major compounds. Two CoTPS21 homologues derived from tandem duplication events were highly expressed during flower development and were identified as the key sesquiterpene synthases for the production of ß-caryophyllene. In addition, CoSPL3 and CoSPL9 were considered as potential transcription factors for activating the expression of CoTPS21 homologues. Our results shed light on the molecular mechanisms underlying the biosynthesis of the unique floral fragrance in C. odorata and provide new insights into the phylogenetic position of magnoliids.

Quantification of Polyphosphate in Environmental Planktonic Samples Using a Novel Fluorescence Dye JC-D7.

Polyphosphate (polyP) is found in plankton of diverse aquatic ecosystems and is important for plankton ecology and biogeochemical cycling. However, our knowledge of polyP in aquatic environments is hindered by a lack of data due to the limitations of quantification methods. The estimate of polyP in model organisms using phenol-chloroform extraction followed by enzymatic hydrolysis is complicated and fails for environmental samples. The commonly used 4',6-diamidino-2-phenylindole (DAPI) fluorescence method for environmental studies, on the contrary, severely overestimates polyP due to interference. In this paper, we develop a plankton lysis buffer to extract polyP and a quantification method using a novel polyP-specific fluorescence dye JC-D7. We test the methods using cultured algae and bacteria, as well as natural samples from marine and freshwater environments. We show that our plankton lysis extracts polyP with high recovery while requiring substantially less time and effort. Subsequent polyP quantification using JC-D7 fluorescence overcomes the interference encountered by the DAPI method and provides an accurate measurement of polyP down to <0.5 µmol L-1. This novel method enables more accurate quantification of polyP in aquatic environments and will profoundly enhance our knowledge of polyP, plankton ecology, and biogeochemistry.

Prediction models for the risk of ventilator-associated pneumonia in patients on mechanical ventilation: A systematic review and meta-analysis.

BACKGROUND: Identifying patients at risk of ventilator-associated pneumonia through prediction models can facilitate medical decision-making. Our objective was to evaluate the current models for ventilator-associated pneumonia in patients with mechanical ventilation. METHODS: Nine databases systematically retrieved from establishment to March 6, 2024. Two independent reviewers performed study selection, data extraction, and quality assessment, respectively. The Prediction Model Risk of Bias Assessment Tool was used to evaluate the risk of model bias and applicability. Stata 17.0 was used to conduct a meta-analysis of discrimination of model validation. RESULTS: The total of 34 studies were included, with reported 52 prediction models. The most frequent predictors in the models were mechanical ventilation duration, length of intensive care unit stay, and age. Each study was essentially considered having a high risk of bias. A meta-analysis of 17 studies containing 33 models with validation was performed with a pooled area under the receiver-operating curve of 0.80 (95% confidence interval: 0.78-0.83). CONCLUSIONS: Despite the relatively excellent performance of the models, there is a high risk of bias of the model development process. Enhancing the methodological quality, especially the external validation, practical application, and optimization of the models need urgent attention.

Neuregulin4-ErbB4 signalling pathway is driven by electroacupuncture stimulation to remodel brown adipose tissue innervation.

AIM: To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)-neuregulin 4 (NRG4)-ErbB4 axis, with somatotopic dependence. MATERIALS AND METHODS: We established a high-fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c-Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B-NRG4-ErbB4 axis was verified by peripheral specific antagonism of ErbB4. RESULTS: ES at the forelimb and abdomen regions significantly up-regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD-induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES. CONCLUSION: These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4-ErbB4 signaling pathway.

Chromosome-level genome assembly of Hippophae rhamnoides variety.

Fructus hippophae (Hippophae rhamnoides spp. mongolica×Hippophae rhamnoides sinensis), a hybrid variety of sea buckthorn that Hippophae rhamnoides spp. mongolica serves as the female parent and Hippophae rhamnoides sinensis serves as the male parent, is a traditional plant with great potentials of economic and medical values. Herein, we gained a chromosome-level genome of Fructus hippophae about 918.59 Mb, with the scaffolds N50 reaching 83.65 Mb. Then, we anchored 440 contigs with 97.17% of the total genome sequences onto 12 pseudochromosomes. Next, de-novo, homology and transcriptome assembly strategies were adopted for gene structure prediction. This predicted 36475 protein-coding genes, of which 36226 genes could be functionally annotated. Simultaneously, various strategies were used for quality assessment, both the complete BUSCO value (98.80%) and the mapping rate indicated the high assembly quality. Repetitive elements, which occupied 63.68% of the genome, and 1483600 bp of non-coding RNA were annotated. Here, we provide genomic information on female plants of a popular variety, which can provide data for pan-genomic construction of sea buckthorn and for the resolution of the mechanism of sex differentiation.

Cold atmospheric plasma in combination with laser therapy provides a window for the treatment of hyperproliferative skin disease.

Modern medical understanding suggests that hyperproliferative skin diseases (HSDs) are complex syndromes characterized by localized hypertrophy or hyperplasia and infiltration of inflammatory cells. Various treatments, including systemic and topical pharmacotherapy, laser interventions, photodynamic therapy, and surgery, have been proposed for managing HSDs. However, challenges such as wound healing and recurrence after laser treatment have hindered the effectiveness of laser therapy. To overcome these challenges, we conducted a study combining laser therapy with cold atmospheric plasma (CAP) for the treatment of HSDs. Seven patients with different forms of HSDs, who had not responded well to conventional treatments, were enrolled in the study. These HSDs included cases of erythroplasia of Queyrat, pyoderma gangrenosum, keloids and hypertrophic scars, cellulitis, cutaneous lichen planus, and verruca vulgaris. Laser therapy was performed to remove the hyperplastic skin lesions, followed immediately by daily CAP treatment. The results were promising, with all patients successfully treated and no recurrence observed during the follow-up periods. The combined application of CAP and laser therapy proved to be an effective and complementary strategy for managing HSDs. This innovative approach provide evidence for addressing the limitation of laser therapy by utilizing CAP to promote wound healing and mitigate inflammatory responses. Chinese Clinical Trial Registry (ChiCTR2300069993).

Characterization of sexual maturity-associated N6-methyladenosine in boar testes.

BACKGROUND: The health and size of the testes are crucial for boar fertility. Testicular development is tightly regulated by epigenetics. N6-methyladenosine (m6A) modification is a prevalent internal modification on mRNA and plays an important role in development. The mRNA m6A methylation in boar testicular development still needs to be investigated. RESULTS: Using the MeRIP-seq technique, we identify and profile m6A modification in boar testes between piglets and adults. The results showed 7783 distinct m6A peaks in piglets and 6590 distinct m6A peaks in adults, with 2,471 peaks shared between the two groups. Enrichment of GO and KEGG analysis reveal dynamic m6A methylation in various biological processes and signalling pathways. Meanwhile, we conjointly analyzed differentially methylated and expressed genes in boar testes before and after sexual maturity, and reproductive related genes (TLE4, TSSK3, TSSK6, C11ORF94, PATZ1, PHLPP1 and PAQR7) were identified. Functional enrichment analysis showed that differential genes are associated with important biological functions, including regulation of growth and development, regulation of metabolic processes and protein catabolic processes. CONCLUSION: The results demonstrate that m6A methylation, differential expression and the related signalling pathways are crucial for boar testicular development. These results suggest a role for m6A modification in boar testicular development and provided a resource for future studies on m6A function in boar testicular development.

Femtosecond Drift Photocurrents Generated by an Inversely Designed Plasmonic Antenna.

Photocurrents play a crucial role in various applications, including light detection, photovoltaics, and THz radiation generation. Despite the abundance of methods and materials for converting light into electrical signals, the use of metals in this context has been relatively limited. Nanostructures supporting surface plasmons in metals offer precise light manipulation and induce light-driven electron motion. Through the inverse design optimization of a gold nanostructure, we demonstrate enhanced volumetric, unidirectional, intense, and ultrafast photocurrents via a magneto-optical process derived from the inverse Faraday effect. This is achieved through fine-tuning the amplitude, polarization, and gradients in the local light field. The virtually instantaneous process allows dynamic photocurrent modulation by varying optical pulse duration, potentially yielding nanosources of intense, ultrafast, planar magnetic fields and frequency-tunable THz emission. These findings open avenues for ultrafast magnetic material manipulation and hold promise for nanoscale THz spectroscopy.

Quercetin induces itaconic acid-mediated M1/M2 alveolar macrophages polarization in respiratory syncytial virus infection.

BACKGROUND: Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive. PURPOSE: This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection. METHODS: BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism. RESULTS: Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes. CONCLUSION: Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.

KLF4 Inhibits the Activation of Human Hepatic Stellate Cell In Vitro.

OBJECTIVE: Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis. Early-stage liver fibrosis is reversible and intimately associated with the state of HSCs. Kruppel-like factor 4 (KLF4) plays a pivotal role in a wide array of physiological and pathological processes. This study aimed to investigate the effect of KLF4 on the proliferation, apoptosis and phenotype of quiescent HSCs METHODS: We designed a KLF4 lentiviral vector and a KLF4 siRNA lentiviral vector, to upregulate and silence KLF4 expression in human HSC LX-2 cells via transfection. Cell proliferation was assessed using the CCK-8 assay. Flow cytometry was used to detect the cell cycle distribution and apoptosis rate. Western blotting was used to determine the levels of some quiescence and activation markers of HSCs RESULTS: Overexpression of KLF4 significantly increased the levels of E-cadherin and ZO-1, which are quiescent HSC markers, while significantly decreased the levels of N-cadherin and a-SMA, known activated HSC markers. In contrast, cell proliferation and apoptosis rates were elevated in LX-2 cells in which KLF4 expression was silenced CONCLUSION: KLF4 inhibits the proliferation and activation of human LX-2 HSCs. It might be a key regulatory protein in the maintenance of HSC quiescence and may serve as a target for the inhibition of hepatic fibrosis.

Dynamic three-dimensional deformation measurement by polarization-multiplexing of full complex amplitude.

This paper provides an extensive discussion of a complex amplitude-based dynamic three-dimensional deformation measurement method, in which the phase and amplitude of the speckle field are used for out-of-plane and in-plane deformation calculation respectively. By determining the optimal polarization states of the speckle field and reference field from the comprehensive analysis of measurement mathematical model in the principle of polarization multiplexing, the 3-step phase-shifting interferograms and one speckle gram can be directly recorded by a polarization camera in a single shot. The out-of-plane deformation would be recovered from the subtraction of speckle phases that are demodulated by a special least square algorithm; speckle gram with improved quality is offered for correlation computation to obtain in-plane deformation. The advancement and significance of the optimized strategy are intuitively demonstrated by comparing the measurement accuracy under different combinations of polarization states. Finally, the dynamic thermal deformation experiment reveals the potential in practical real-time applications.

Identification of shared gene signatures and biological mechanisms between preeclampsia and polycystic ovary syndrome.

Preeclampsia (PE) is one of the most common complications of pregnancy and polycystic ovary syndrome (PCOS) is a prevalent metabolic and endocrinopathy disorder in women of reproductive age. Identifying the shared genetic signatures and molecular mechanisms between PCOS and PE was the objective of this study. The intersections of WGCNA module genes, PPI module genes, and PPI hub genes revealed that 8 immunity-related genes might be shared causative genes of PE and PCOS. Further, qRT-PCR results showed that TSIX/miR-223-3p/DDX58 might play a crucial role in immune dysregulation in PE and PCOS and Spearman rank correlation analysis results illustrated the potential of DDX58 as a novel diagnostic and therapeutic target for PE and PCOS. Our study demonstrated a common disease pathway model TSIX/miR-223-3p/DDX58, illustrating that immune dysregulation may be a possible mechanism of PE and PCOS, and revealed that DDX58 might be a novel predictive target for PE and PCOS.

In vitro study of cold atmospheric plasma-activated liquids inhibits malignant melanoma by affecting macrophage polarization through the ROS/JAK2/STAT1 pathway.

Melanoma is a prevalent malignant skin tumor known for its high invasive ability and a high rate of metastasis, making clinical treatment exceptionally challenging. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment and play a crucial role in tumor survival and development. Cold atmospheric plasma (CAP) is an emerging tool for tumor treatment that has garnered attention from scholars due to its interaction with non-tumor cells in the tumor microenvironment. Here, we used the macrophage lines THP-1 and RAW264.7, as well as the melanoma cell lines A375 and MV3, as research subjects to investigate the effect of plasma-activated liquid (PAL) on macrophage differentiation and its inhibitory effect on melanoma cell proliferation. We confirmed that the killing effect of PAL on melanoma cells was selective. Using flow cytometry and PCR, we discovered that PAL can influence macrophage differentiation. Through in vitro cell coculture, we demonstrated that PAL-treated macrophages can significantly impede tumor cell development and progression, and the effect is more potent than that of PAL directly targeting tumor cells. Furthermore, we have proposed the hypothesis that PAL promotes the differentiation of macrophages into the M1 type through the ROS/JAK2/STAT1 pathway. To test the hypothesis, we employed catalase and fludarabine to block different sites of the pathway. The results were then validated through Western Blot, qPCR and ELISA. This study illustrates that PAL therapy is an effective tumor immunotherapy and expands the scope of tumor immunotherapy. Furthermore, these findings establish a theoretical foundation for potential clinical applications of PAL.

SPRY1 Deficiency in Keratinocytes Induces Follicular Melanocyte Stem Cell Migration to the Epidermis through p53/Stem Cell Factor/C-KIT Signaling.

The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes (KCs). KCs and melanocytes respond to UV exposure by eliciting a tanning response. However, how KCs and melanocytes interact in the absence of UV exposure is unknown. In this study, we demonstrate that after SPRY1 knockout in epidermal KCs, melanocyte stem cells in the hair follicle exit the niche without depleting the pool of these cells. We also found that melanocyte stem cells migrate to the epidermis in a p53/stem cell factor/C-KIT-dependent manner induced by a tanning-like response resulting from SPRY1 loss in epidermal KCs. Once there, these cells differentiate into functional melanocytes. These findings provide an example in which the migration of melanocyte stem cells to the epidermis is due to loss of SPRY1 in epidermal KCs and show the potential for developing therapies for skin pigmentation disorders by manipulating melanocyte stem cells.

Efficient Method for Numerical Calculations of Molecular Vibrational Frequencies by Exploiting Sparseness of Hessian Matrix.

Molecular vibrational frequency analysis plays an important role in theoretical and computational chemistry. However, in many cases, the analytical frequencies are unavailable, whereas frequency calculations using conventional numerical methods are very expensive. In this work, we propose an efficient method to numerically calculate the frequencies. Our main strategies are to exploit the sparseness of the Hessian matrix and to construct the N-fold two-variable potential energy surfaces to fit the parabola parameters, which are later used for the construction of Hessian matrices. A set of benchmark calculations is performed for typical molecules of different sizes and complexities using the proposed method. The obtained frequencies are compared to those calculated with the analytical methods and conventional numerical methods. It is shown that the results yielded with the new method are in very good agreement with corresponding accurate values (with a maximum error of ∼20 cm-1), while the required computation resource is largely reduced compared to that required by conventional numerical methods. For medium-sized molecules, the calculational scaling is lowered to O(N1.6) (this work) from that of O(N2) (conventional numerical methods). For even larger molecules, more computational savings can be achieved, and the scaling is estimated to be quasilinear with respect to the molecular size.

Mining Heat-Resistant Key Genes of Peony Based on Weighted Gene Co-Expression Network Analysis.

The RNA-Seq and gene expression data of mature leaves under high temperature stress of Paeonia suffruticosa 'Hu Hong' were used to explore the key genes of heat tolerance of peony. The weighted gene co-expression network analysis (WGCNA) method was used to construct the network, and the main modules and core genes of co-expression were screened according to the results of gene expression and module function enrichment analysis. According to the correlation of gene expression, the network was divided into 19 modules. By analyzing the expression patterns of each module gene, Blue, Salmon and Yellow were identified as the key modules of peony heat response related functions. GO and KEGG functional enrichment analysis was performed on the genes in the three modules and a network diagram was constructed. Based on this, two key genes PsWRKY53 (TRINITY_DN60998_c1_g2, TRINITY_DN71537_c0_g1) and PsHsfB2b (TRINITY_DN56794_c0_g1) were excavated, which may play a key role in the heat shock response of peony. The three co-expression modules and two key genes were helpful to further elucidate the heat resistance mechanism of P. suffruticosa 'Hu Hong'.

Association of maternal serum uric acid levels with LBW/SGA: a large retrospective cohort study.

BACKGROUND: Elevated maternal serum uric acid (UA) levels were associated with adverse perinatal outcomes. This study aimed to examine the association between UA and the risk of low birth weight (LBW) / small for gestational age (SGA). METHODS: A cohort study of women delivered in Shanghai maternity hospital was included between 2017 and 2021. Electronic medical records were utilized to extract information and antenatal care records. The cut-off value of UA was 360 µmol/L. The outcome was LBW/SGA, with LBW defined as birth weight below 2500 g and SGA indicating birth weight below the 10th percentile of average weight for gestational age. The assessment of SGA was based on the Chinese standard curve for birth weight at various gestational ages. Univariate, multivariate logistic regression models, restricted cubic spline were used in this study, with adjustments made for confounding factors. RESULTS: Sixty-nine thousand six hundred seventy-four live births and singleton pregnancies were included. The ratio of LBW/SGA was 3.3%/9%. Maternal UA levels were significantly negatively correlated with birth weight. High UA levels were associated with high risk of LBW/SGA, especially in third trimester. In BMI < 25 group, the risk of LBW increased to 2.35-fold (95%CI, 1.66-3.31) in hyperuricemic group (UA > 360 µmol/L). The SGA risk was 1.66-fold (95%CI, 1.37-2.00). Gestational hypertension (GH) with hyperuricemica increased the risk of LBW (aOR = 4.00, 95%CI, 2.01-7.93) and SGA (aOR = 2.63, 95%CI, 1.83-3.78). Preeclampsia (PE) with hyperuricemia increased the risk of LBW (aOR = 1.38, 95%CI, 0.63-3.03) and SGA (aOR = 1.81, 95%CI, 1.18-2.78). In delivery gestational week (DGW) ≥ 37 group, if UA > 360 µmol/L, the incidence of LBW increased to 2.46-fold (95%CI, 1.62, 3.73) and the incidence of SGA increased to 1.52-fold (95%CI, 1.24, 1.87). In DGW < 37 group, if UA > 360 µmol/L, the incidence of LBW increased to 2.70-fold (95%CI, 1.92, 3.80) and the incidence of SGA increased to 2.13-fold(95%CI, 1.50, 3.02). CONCLUSIONS: The study found an inverse correlation between UA levels and birth weight. High UA levels were associated with increased risk of LBW/SGA, particularly in third trimester. GH or PE complicated by hyperuricemia were found to have significantly higher risk of developing LBW/SGA. This relationship also existed in pregnant women with BMI < 25.

A novel magnetic resonance tuning-magnetic relaxation switching sensor based on Gd-MOF/USPIO assembly for sensitive and convenient aflatoxin B1 detection.

Aflatoxin B1 (AFB1) can accumulate in different organs or tissues and seriously harm humans. Traditional magnetic relaxation switching (MRS) sensors have relatively low sensitivity, but are complex to use. Rapid small-trace molecule analysis in complex samples is challenging. In this study, we used a gadolinium-based metal-organic framework (Gd-MOF) and ultra-small superparamagnetic iron oxide (USPIO) assembly to develop a magnetic resonance tuning-magnetic relaxation switching (MRET-MRS) sensor to improve conventional MRS sensor sensitivity and simplify operational steps in complex samples. Importantly, the local magnetic field generated by USPIO interfered with Gd-MOF electron spin fluctuation and directly affected dipole-dipole interactions between Gd electrons and water molecules, thus rendering relaxation signal changes more sensitive. The sensitivity (0.54 pg mL-1) was 833 times more sensitive than that of a conventional MRS sensor (0.45 ng mL-1). Finally, a convenient one-step detection approach can be achieved by mixing antigen/antibody functionalized Gd-MOF/USPIO and target samples.

Remodelling the inguinal adipose sensory system to switch on the furnace: Electroacupuncture stimulation induces brown adipose thermogenesis.

Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the associated molecular mechanisms are lacking. We investigated body surface electroacupuncture stimulation (ES) at ST25 (targeted at the abdomen) induction of brown adipose thermogenesis and the neural mechanism of this process. Inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) were collected and the thermogenic protein expression levels were measured to evaluate iBAT thermogenesis capacity. The thermogenic centre activating region and sympathetic outflow were evaluated based on neural electrical activity and c-fos expression levels. iWAT sensory axon plasticity was analysed with whole-mount adipose tissue imaging. ES activated the sympathetic nerves in iBAT and the c-fos-positive cells induced sympathetic outflow activation to the iBAT from the medial preoptic area (MPA), the dorsomedial hypothalamus (DM) and the raphe pallidus nucleus (RPA). iWAT denervation mice exhibited decreased c-fos-positive cells in the DM and RPA, and lower recombinant uncoupling orotein 1 peroxisome proliferator-activated receptor, ß3-adrenergic receptor, and tyrosine hydroxylase expression. Remodelling the iWAT sensory axons recovered the signal from the MPA to the RPA and induced iBAT thermogenesis. The sympathetic denervation attenuated sensory nerve density. ES induced sympathetic outflow from the thermogenetic centres to iBAT, which mediated thermogenesis. iWAT sensory axon remodelling induced the MPA-DM-RPA-iBAT thermogenesis pathway.