Peroxynitrite-Triggered Carbon Monoxide Donor Improves Ischemic Stroke Outcome by Inhibiting Neuronal Apoptosis and Ferroptosis.

Cerebral ischemia-reperfusion injury produces excessive reactive oxygen and nitrogen species, including superoxide, nitric oxide, and peroxynitrite (ONOO-). We recently developed a new ONOO--triggered metal-free carbon monoxide donor (PCOD585), exhibiting a notable neuroprotective outcome on the rat middle cerebral artery occlusion model and rendering an exciting intervention opportunity toward ischemia-induced brain injuries. However, its therapeutic mechanism still needs to be addressed. In the pharmacological study, we found PCOD585 inhibited neuronal Bcl2/Bax/caspase-3 apoptosis pathway in the peri-infarcted area of stroke by scavenging ONOO-. ONOO- scavenging further led to decreased Acyl-CoA synthetase long-chain family member 4 and increased glutathione peroxidase 4, to minimize lipoperoxidation. Additionally, the carbon monoxide release upon the ONOO- reaction with PCOD585 further inhibited the neuronal Iron-dependent ferroptosis associated with ischemia-reperfusion. Such a synergistic neuroprotective mechanism of PCOD585 yields as potent a neuroprotective effect as Edaravone. Additionally, PCOD585 penetrates the blood-brain barrier and reduces the degradation of zonula occludens-1 by inhibiting matrix metalloproteinase-9, thereby protecting the integrity of the blood-brain barrier. Our study provides a new perspective for developing multi-functional compounds to treat ischemic stroke.

A Carbon-Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy.

Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e- oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2 -), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2 - is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO2 - generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2 -, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.

Combination of S100A12/TLR2 signaling molecules and clinical indicators in a new predictive model for IVIG-resistant Kawasaki disease.

Although intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) presents with persistent inflammatory stimulation of the blood vessels and an increased risk of coronary artery dilatation. However, the pathogenesis of this disease is unclear, with no established biomarkers to predict its occurrence. This study intends to explore the utility of S100A12/TLR2-related signaling molecules and clinical indicators in the predictive modeling of IVIG-resistant KD. The subjects were classified according to IVIG treatment response: 206 patients in an IVIG-sensitive KD group and 49 in an IVIG-resistant KD group. Real-time PCR was used to measure the expression of S100A12, TLR2, MYD88, and NF-κB in peripheral blood mononuclear cells of patients, while collecting demographic characteristics, clinical manifestations, and laboratory test results of KD children. Multi-factor binary logistic regression analysis identified procalcitonin (PCT) level (≥ 0.845 ng/mL), Na level (≤ 136.55 mmol/L), and the relative expression level of S100A12 (≥ 10.224) as independent risk factors for IVIG-resistant KD and developed a new scoring model with good predictive ability to predict the occurrence of IVIG-resistant KD.

Melatonin restores DNFB-induced dysbiosis of skin microbiota in a mouse model of atopic dermatitis.

BACKGROUND: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear. METHODS: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing. RESULTS: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut. CONCLUSION: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus.

Acyl-caged rhodamines: photo-controlled and self-calibrated generation of acetyl radicals for neural function recovery in early AD mice.

The biological function of radicals is a broad continuum from signaling to killing. Yet, biomedical exploitation of radicals is largely restricted to the theme of healing-by-killing. To explore their potential in healing-by-signaling, robust radical generation methods are warranted. Acyl radicals are endogenous, exhibit facile chemistry and elicit matrix-dependent biological outcomes. Their implications in health and disease remain untapped, primarily due to the lack of a robust generation method with spatiotemporal specificity. Fusing the Norrish chemistry into the xanthene scaffold, we developed a novel general and modular molecular design strategy for photo-triggered generation of acyl radicals, i.e., acyl-caged rhodamine (ACR). A notable feature of ACR is the simultaneous release of a fluorescent probe for cell redox homeostasis allowing real-time monitoring of the biological outcome of acyl radicals. With a donor of the endogenous acetyl radical (ACR575a), we showcased its capability in precise and continuous modulation of the cell redox homeostasis from signaling to stress, and induction of a local oxidative burst to promote differentiation of neural stem cells (NSCs). Upon intracerebral-injection of ACR575a and subsequent fiber-optical activation, early AD mice exhibited enhanced differentiation of NSCs toward neurons, reduced formation of Aß plaques, and significantly improved cognitive abilities, including learning and memory.

Clinical indicators combined with S100A12/TLR2 signaling molecules to establish a new scoring model for coronary artery lesions in Kawasaki disease.

Coronary artery lesions (CALs) are the most common and serious complication of Kawasaki disease (KD), and the pathogenesis is unknown. Exploring KD-specific biomarkers and related risk factors is significant for clinical diagnosis and treatment. This study aimed to explore the feasibility of combining clinical indicators with S100A12/TLR2-associated signaling molecules for the predictive modeling of CALs in KD. A total of 346 patients (224 males and 122 females) with KD who visited the rheumatology department of Wuhan Children's Hospital between April 2022 and March 2025 were enrolled and divided into two groups according to the presence or absence of CALS (292 patients had CALs and 54 patients did not). Forty-one variables were collected from the two groups, including demographic characteristics, clinical manifestations, and laboratory data. Single nucleated cells from each patient were extracted, and the expression of the S100A12/TLR2 signal transduction-related molecules S100A12, TLR2, MYD88, and NF-κB were detected by real-time fluorescent quantitative polymerase chain reaction. Statistically significant variables were subjected to logistic regression analysis to determine the independent risk factors for KD with CALs, and a new risk score model was established to assess the predictive efficacy based on receiver operating characteristic curves. Sixteen variables significantly differed between the no-CALs and CALs groups: gender, fever duration, white blood cells (WBC), hemoglobin (HGB), Ce reactive protein (CRP), procalcitonin, serum ferritin (SF), erythrocyte sedimentation rate (ESR), fibrinogen (FIB), aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT), serum albumin (ALB), sodium (Na), Interleukin (IL-10), tumor necrosis factor (TNF-α), S100 calcium binding protein A12 (S100A12), and Myeloid Differentiation Factor 88 (MYD88) (p < 0.05). After performing a univariate analysis, 12 variables (gender, fever duration, WBC, HGB, CRP, SF, ESR, FIB, AST/ALT, ALB, Na, and S100A12) were included in the multifactorial binary logistic regression, which showed that fever duration ≥ 6.5 days, ESR ≥ 46.5 mm/h, AST/ALT ≤ 1.51, and S100A12 ≥ 10.02 were independent risk factors for KD with CALs and were assigned scores of 3, 2, 1, and 2, respectively, according to the odds ratio (OR). The total score of each patient was counted, and a new prediction model for KD combined with CALs was established, where < 3.5 was considered low risk and ≥ 3.5 was regarded as high risk; the sensitivity, specificity, Jorden index, and area under the curve of this scoring system were 0.667, 0.836, 0.502, and 0.838, respectively. This new scoring model has good efficacy for predicting the occurrence of KD with CALs. The expression of S100A12 was significantly increased in the CALs group and was an independent risk factor for the occurrence of CALs, and has the potential as a biomarker for predicting KD with CALs.

Restoring prefrontal cortical excitation-inhibition balance with cannabidiol ameliorates neurobehavioral abnormalities in a mouse model of neurodevelopmental disorders.

Maternal immune activation (MIA) resulting from viral infections during pregnancy is linked to increased rates of neurodevelopmental disorders in offspring. However, the mechanisms underlying MIA-induced neurobehavioral abnormalities remain unclear. Here, we used a poly (I:C)-induced MIA mouse model to demonstrate the presence of multiple behavioral deficits in male offspring. Through RNA sequencing (RNA-seq), we identified significant upregulation of genes involved in axonogenesis, synaptogenesis, and glutamatergic synaptic neurotransmission in the mPFC of MIA mice. Electrophysiological analyses further revealed an excitatory-inhibitory (E/I) synaptic imbalance in mPFC pyramidal neurons, leading to hyperactivity in this brain region. Cannabidiol (CBD) effectively alleviated the behavioral abnormalities observed in MIA offspring by reducing glutamatergic transmission and enhancing GABAergic neurotransmission of mPFC pyramidal neurons. Activation of GPR55 by lipid lysophosphatidylinositol (LPI), an endogenous GPR55 agonist, specifically in the mPFC of healthy animals led to MIA-associated behavioral phenotypes, which CBD could effectively reverse. Moreover, we found that a GPR55 antagonist can mimic CBD's beneficial effects, indicating that CBD's therapeutic effects are mediated via the LPI-GPR55 signaling pathway. Therefore, we identified mPFC as a primary node of a neural network that mediates MIA-induced behavioral abnormalities in offspring. Our work provides insights into the mechanisms underlying the developmental consequences of MIA and identifies CBD as a promising therapeutic approach to alleviate these effects.

A High-Density Raman Photometry for Tracking and Quantifying of AchE Activity in The Brain of Freely Moving Animals with Network.

A high-density Raman photometry based on a dual-recognition strategy is created for accurately quantifying acetylcholinesterase (AchE) activity in 24 brain regions of free-moving animals with network. A series of 5-ethynyl-1,2,3,3-tetramethyl-based molecules with different conjugated structures and substitute groups are designed and synthesized for specific recognition of AchE by Raman spectroscopy. After systematically evaluating the recognition ability toward AchE, 2-(4-((4-(dimethylamino)benzoyl)oxy)styryl)-5-ethynyl-1,3,3-trimethyl-3H-indol-1-ium (ET-5) is finally optimized for AchE determination, which shows the highest selectivity, the greatest sensitivity, and the fastest response time among the investigated seven molecules. More interestingly, using the developed probe for AchE with high accuracy and sensitivity, the optimized AchE regulated by nitric oxide (NO) is discovered for promoting the neurogenesis of neural stem cells (NSCs). Benefiting from the high-density photometry, it is found that the activity and distribution of AchE varied in 24 brain regions, and the levels of AchE activity in 24 brain regions of Alzheimer's mice (AD) are lower than those of normal mice. It is the first time that a functional network of AchE in 24 brain regions is established. It is also found that the loss of AchE functional network in AD mice is restored and reconstructed by the controlled release of AchE regulated by NO.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

An ischemic area-targeting, peroxynitrite-responsive, biomimetic carbon monoxide nanogenerator for preventing myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion (MI/R) injury is common in patients who undergo revascularization therapy for myocardial infarction, often leading to cardiac dysfunction. Carbon monoxide (CO) has emerged as a therapeutic molecule due to its beneficial properties such as anti-inflammatory, anti-apoptotic, and mitochondrial biogenesis-promoting properties. However, its clinical application is limited due to uncontrolled release, potential toxicity, and poor targeting efficiency. To address these limitations, a peroxynitrite (ONOO-)-triggered CO donor (PCOD585) is utilized to generate a poly (lactic-co-glycolic acid) (PLGA)-based, biomimetic CO nanogenerator (M/PCOD@PLGA) that is coated with the macrophage membrane, which could target to the ischemic area and neutralize proinflammatory cytokines. In the ischemic area, local produced ONOO- triggers the continuous release of CO from M/PCOD@PLGA, which efficiently ameliorates MI/R injury by clearing harmful ONOO-, attenuating the inflammatory response, inhibiting cardiomyocyte apoptosis, and promoting mitochondrial biogenesis. This study provides a novel insight into the safe therapeutic use of CO for MI/R injury by utilizing a novel CO donor combined with biomimetic technology. The M/PCOD@PLGA nanogenerator offers targeted delivery of CO to the ischemic area, minimizing potential toxicity and enhancing therapeutic efficacy.

PET/d-PET (PdP) Pairing for the Design of Dual-Channel Probes.

Design principles of two-channel fluorescence probes are limited. Herein, we report a new principle, i.e., PET/d-PET (PdP) pairing, for the rational design of two-channel probes. Two fluorophores are required in such a PdP-type probe. They mutually quench their fluorescence via PET and d-PET. In the presence of an analyte-of-interest, such a PdP pair is converted into a FRET pair for signaling. The embodiment of such a principle is Rh-TROX, by tethering a rhodamine fluorophore with an ROS-sensitive probe (TotalROX). Fluorescence of both fluorophores in Rh-TROX was quenched as expected. The addition of highly reactive oxidative species led to the recovery of the fluorescence properties of both. The simultaneous fluorescence enhancement in two channels is a viable way to avoid false-positive signals. The new PdP principle could potentially be applied to the development of probes for another range of substrates.

Impact of plastic film mulching on microplastic in farmland soils in Guangdong province, China.

Plastic mulch film is often believed to be a significant contributor to microplastic pollution in farmland soil, however, its direct impact in areas with high human activities remains unclear due to the presence of multiple pollution sources. This study aims to address this knowledge gap by investigating the impact of plastic film mulching on microplastic pollution in farmland soils in Guangdong province, China's largest economic province. The macroplastic residues in soils were investigated in 64 agricultural sites, and the microplastics were analyzed in typical plastic film mulched and nearby non-mulched farmland soils. The average concentration of macroplastic residues was 35.7 kg/ha and displayed a positive correlation with mulch film usage intensity. Contrarily, no significant correlation was found between macroplastic residues and microplastics, which exhibited an average abundance of 22,675 particles/kg soil. The pollution load index (PLI) model indicated that the microplastic pollution level was category I and comparatively higher in mulched farmland soils. Interestingly, polyethylene accounted for only 2.7% of the microplastics, while polyurethane was found to be the most abundant microplastic. According to the polymer hazard index (PHI) model, polyethylene posed a lower environmental risk than polyurethane in both mulched and non-mulched soils. These findings suggest that multiple sources other than plastic film mulching primarily contribute to microplastic pollution in farmland soils. This study enhances our understanding of microplastic sources and accumulation in farmland soils, offering crucial information on potential risks to the agroecosystem.

Rigid and Photostable Shortwave Infrared Dye Absorbing/Emitting beyond 1200 nm for High-Contrast Multiplexed Imaging.

The shortwave infrared (SWIR) spectral region beyond 1200 nm offers optimal tissue penetration depth and has broad potential in diagnosis, therapy, and surgery. Here, we devised a novel class of fluorochromic scaffold, i.e., a tetra-benzannulated xanthenoid (EC7). EC7 absorbs/emits maximally at 1204/1290 nm in CH2Cl2 and exhibits an unparalleled molar absorptivity of 3.91 × 105 cm-1 M-1 and high transparency to light at 400-900 nm. It also exhibited high resistance toward both photobleaching and symmetry breaking due to its unique structural rigidity. It is feasible for in vivo bioimaging and particularly suitable to couple with the shorter-wavelength analogues for high-contrast multiplexing. High-contrast dual-channel intraoperative imaging of the hepatobiliary system and three-channel in vivo imaging of the intestine, the stomach, and the vasculature were showcased. EC7 is a benchmark fluorochrome for facile biomedical exploitation of the SWIR region beyond 1200 nm.

Activation of D1R signaling in the medial prefrontal cortex rescues maternal separation-induced behavioral deficits through restoration of excitatory neurotransmission.

Lack of maternal care and attention during infancy and childhood increases the likelihood of developing a range of neuropsychiatric disorders, such as social deficits, working memory impairment, and anxiety-like behaviors, in adulthood. However, the neuroregulatory signaling through which early-life stress causes behavioral and cognitive abnormalities in the offspring is largely unexplored. Here, we show that in mice, unpredictable maternal separation (MS) during the early postnatal period impairs neuronal development in the medial prefrontal cortex (mPFC) and results in long-lasting behavioral changes. Additionally, MS disrupts excitatory neurotransmission and inhibits the neuronal activity of pyramidal neurons in the mPFC. Differentially expressed gene (DEG) analysis of RNA sequencing (RNA-seq) data of mPFC showed that dopamine D1 receptor (D1R) was significantly downregulated in MS animals. Finally, we show that pharmacological activation of D1R signaling specifically in the mPFC improves neuronal excitability and rescues behavioral and cognitive dysfunction of MS mice, whereas pharmacologically inhibiting of D1R in the mPFC mimics MS-induced behavioral abnormalities in control mice. Together, our results identify D1R signaling in the mPFC, at least in part, as a potential therapeutic target for the behavioral and cognitive abnormalities caused by deprivation of maternal care in early life.

Hill-type pH probes.

Sensitive detection of the minute and yet pathologically significant pH variation is important and in fact challenging for the conventional pH probes following the Henderson-Hasselbalch equation, i.e., HH-type probes. A paradigm shift to Hill-type pH probes is ongoing. Bestowed by their positive cooperative acid-base chemistry, their pH-responsive profile follows the Hill equation, which exhibits a narrower acid/base transition width than HH-type probes and warrants a higher detection sensitivity. A polymer-based Hill-type pH-responsive material was first developed. More recently, there emerged several distinct small-molecular approaches to achieve Hill-type pH-responsive profiles. They complement the polymer-based sensing materials in applications where membrane permeability is a concern. In this trends article, we rationalize the molecular origins of their positive cooperativity in pH sensing and highlight some interesting proof-of-concept applications. We also discussed future directions of this dynamic research area.

Maslinic Acid: A New Compound for the Treatment of Multiple Organ Diseases.

Maslinic acid (MA) is a pentacyclic triterpene acid, which exists in many plants, including olive, and is highly safe for human beings. In recent years, it has been reported that MA has anti-inflammatory, antioxidant, anti-tumor, hypoglycemic, neuroprotective and other biological activities. More and more experimental data has shown that MA has a good therapeutic effect on multiple organ diseases, indicating that it has great clinical application potential. In this paper, the extraction, purification, identification and analysis, biological activity, pharmacokinetics in vivo and molecular mechanism of MA in treating various organ diseases are reviewed. It is hoped to provide a new idea for MA to treat various organ diseases.

Cardiolipin-Targeted NIR-II Fluorophore Causes "Avalanche Effects" for Re-Engaging Cancer Apoptosis and Inhibiting Metastasis.

Restoring innate apoptosis and simultaneously inhibiting metastasis by a molecular drug is an effective cancer therapeutic approach. Herein, a large rigid and V-shaped NIR-II dye, DUT850, is rationally designed for potential cardiolipin (CL)-targeted chemo-phototheranostic application. DUT850 displays moderate NIR-II fluorescence, excellent photodynamic therapy (PDT) and photothermal therapy (PTT) performance, and ultra-high photostability. More importantly, the unique rigid V-shaped backbone, positive charge, and lipophilicity of DUT850 afford its specific recognition and efficient binding to CL; such an interaction of DUT850-CL induced a spectrum of physiological disruptions, including translocation of cytochrome c, Ca2+ overload, reactive oxygen species burst, and ATP depletion, which not only activated cancer cell apoptosis but also inhibited tumor metastasis both in vitro and in vivo. Furthermore, the tight binding of DUT850-CL improves the phototoxicity of DUT850 toward cancer cells (IC50 as low as 90 nM) under safe 808 nm laser irradiation (330 mW cm-2). Upon encapsulation into bovine serum albumin (BSA), DUT850@BSA exerted a synergetic chemo-PDT-PTT effect on the 4T1 tumor mouse model, eventually leading to solid tumor annihilation and metastasis inhibition, which could be followed in real time with the NIR-II fluorescence of DUT850. This work contributed a promising approach for simultaneously re-engaging cancer cell apoptotic networks and activating the anti-metastasis pathway by targeting a pivotal upstream effector, which will bring a medical boon for inhibition of tumor proliferation and metastasis.

Xiaoyao San ameliorates high-fat diet-induced anxiety and depression via regulating gut microbiota in mice.

Obesity, a growing health problem in the world, is related to a series of mental disorders, including anxiety and depression. XiaoYao San (XYS), a prescription of traditional Chinese medicine (TCM), has been widely used in the clinical treatment of anxiety and depression in China. However, the efficacy of XYS on obesity-related neuropsychiatric dysfunction and the underlying neural mechanisms remain unclear. Here, using a high-fat diet (HFD)-induced obese model, we found that XYS treatment significantly improves obesity-related anxiety- and depression-like behaviors and alters the gut microbiome, particularly by increasing the relative abundance of Faecalibaculum rodentium (F. rodentium), in mice. Interestingly, selective supplementation with F. rodentium or its metabolic products, short-chain fatty acids (SCFAs), is sufficient to rescue anxiety- and depression-like behaviors in HFD-fed mice. Next, we determined that the transcriptional level of dopamine D2 receptor (DRD2), which activation usually inhibits inflammation in the central nervous system (CNS), is significantly increased in the medial prefrontal cortex (mPFC) of XYS-treated mice when compared with that of vehicle-treated controls. Moreover, enriched pathways analysis with the differential expression genes (DEGs) showed that some of these DEGs are enriched in neuroinflammatory pathways. We further noticed that treatment with XYS contributes to controlling microglial activation and proinflammatory responses in the mPFC and hippocampus of HFD-fed mice. Overall, this study reveals that XYS rescues HFD-induced anxiety and depression via modulating gut microbiota-derived metabolites and that XYS is a potential therapeutic strategy for treating obesity-associated mental disorders.

Electroacupuncture promoted intestinal defensins and rescued the dysbiotic cecal microbiota of high-fat diet-induced obese mice.

Obesity is currently one of the most important challenges to public health worldwide. Acupuncture has been widely used to treat obesity. However, whether acupuncture regulates intestinal innate immunity via intestinal microbiota against obesity remains to be elucidated. In this study, electroacupuncture (EA) effectively reduced body weight and fat accumulation in obese mice persistently fed a high-fat diet. Full-length 16S rDNA sequencing showed dysbiotic microbiota in the cecum of obese mice. The composition and function of the cecal microbiota of obese mice were markedly restored after EA treatment. After 21 d of EA intervention, the expression of defensin alpha 5 (Defa5) was restored to healthy controls, whereas fat digestion and absorption genes including fabp1 were markedly decreased in the jejunum of obese mice. The Defa5 levels were positively correlated with the family Lachnospiraceae and negatively correlated with obesity indexes. EA also reduced tissue inflammation, ameliorated misaligned glucose tolerance, and inhibited key genes for intestinal lipid absorption. In summary, EA exerted an anti-obesity effect by promoting intestinal defensins, rescuing dysbiotic cecal microbiota, and reducing lipid absorption in a synergistic mode. We present for the first time the key role of alpha defensins in the relationship between gut microbiota and disease during electroacupuncture treatment of obesity. The mucosal innate immunity seems to have a stronger ability to shape the microbiota than dietary factors.

Stable, Bright, and Long-Fluorescence-Lifetime Dyes for Deep-Near-Infrared Bioimaging.

Near-infrared (NIR) fluorophores absorbing maximally in the region beyond 800 nm, i.e., deep-NIR spectral region, are actively sought for biomedical applications. Ideal dyes are bright, nontoxic, photostable, biocompatible, and easily derivatized to introduce functionalities (e.g., for bioconjugation or aqueous solubility). The rational design of such fluorophores remains a major challenge. Silicon-substituted rhodamines have been successful for bioimaging applications in the red spectral region. The longer-wavelength silicon-substituted congeners for the deep-NIR spectral region are unknown to date. We successfully prepared four silicon-substituted bis-benzannulated rhodamine dyes (ESi5a-ESi5d), with an efficient five-step cascade on a gram-scale. Because of the extensive overlapping of their HOMO-LUMO orbitals, ESi5a-ESi5d are highly absorbing (λabs ≈ 865 nm and ε > 105 cm-1 M-1). By restraining both the rotational freedom via annulation and the vibrational freedom via silicon-imparted strain, the fluorochromic scaffold of ESi5 is highly rigid, resulting in an unusually long fluorescence lifetime (τ > 700 ps in CH2Cl2) and a high fluorescence quantum yield (ϕ = 0.14 in CH2Cl2). Their half-lives toward photobleaching are 2 orders of magnitude longer than the current standard (ICG in serum). They are stable in the presence of biorelevant concentration of nucleophiles or reactive oxygen species. They are minimally toxic and readily metabolized. Upon tail vein injection of ESi5a (as an example), the vasculature of a nude mouse was imaged with a high signal-to-background ratio. ESi5 dyes have broad potentials for bioimaging in the deep-NIR spectral region.