Decoding the influence of low temperature on biofilm development: The hidden roles of c-di-GMP.

Biofilms are widely used and play important roles in biological processes. Low temperature of wastewater inhibits the development of biofilms derived from wastewater activated sludge. However, the specific mechanism of temperature on biofilm development is still unclear. This study explored the mechanism of temperature on biofilm development and found a feasible method to enhance biofilm development at low temperature. The amount of biofilm development decreased by approximately 66 % and 55 % at 4 °C and 15 °C, respectively, as compared to 28 °C. The cyclic dimeric guanosine monophosphate (c-di-GMP) concentration also decreased at low temperature and was positively correlated with extracellular polymeric substance (EPS) content, formation, and adhesion strength. Microbial community results showed that low temperature inhibited the normal survival of most microorganisms, but promoted the growth of some psychrophile bacteria like Sporosarcina, Caldilineaceae, Gemmataceae, Anaerolineaceae and Acidobacteriota. Further analysis of functional genes demonstrated that the abundance of functional genes related to the synthesis of c-di-GMP (K18968, K18967 and K13590) decreased at low temperature. Subsequently, the addition of exogenous spermidine increased the level of intracellular c-di-GMP and alleviated the inhibition effect of low temperature on biofilm development. Therefore, the possible mechanism of low temperature on biofilm development could be the inhibition of the microorganism activity and reduction of the communication level between cells, which is the closely related to the EPS content, formation, and adhesion strength. The enhancement of c-di-GMP level through the exogenous addition of spermidine provides an alternative strategy to enhance biofilm development at low temperatures. The results of this study enhance the understanding of the influence of temperature on biofilm development and provide possible strategies for enhancing biofilm development at low temperatures.

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1ß and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.

Single-cell RNA sequencing reveals cell type-specific immune regulation associated with human neuromyelitis optica spectrum disorder.

Introduction: One rare type of autoimmune disease is called neuromyelitis optica spectrum disorder (NMOSD) and the peripheral immune characteristics of NMOSD remain unclear. Methods: Here, single-cell RNA sequencing (scRNA-seq) is used to characterize peripheral blood mononuclear cells from individuals with NMOSD. Results: The differentiation and activation of lymphocytes, expansion of myeloid cells, and an excessive inflammatory response in innate immunity are observed. Flow cytometry analyses confirm a significant increase in the percentage of plasma cells among B cells in NMOSD. NMOSD patients exhibit an elevated percentage of CD8+ T cells within the T cell population. Oligoclonal expansions of B cell receptors are observed after therapy. Additionally, individuals with NMOSD exhibit elevated expression of CXCL8, IL7, IL18, TNFSF13, IFNG, and NLRP3. Discussion: Peripheral immune response high-dimensional single-cell profiling identifies immune cell subsets specific to a certain disease and identifies possible new targets for NMOSD.

Lumbar disc herniation is an independent predictor of plaque burden in the patients with unstable angina.

Objective: Assessing the impact of lumbar disc herniation (LDH) on the plaque burden of coronary atherosclerosis is our objective. Methods: In this study, a total of 212 patients (age 46-80 years) with unstable angina (UA) who underwent coronary angiography (CAG) in our hospital from January 2018 to July 2022 due to UA were included. Patients were divided into LDH group (n = 106) and no LDH group (n = 106). Gensini scores were calculated to assess the plaque burden of coronary. Logistic analysis was used to examine potential risk variables linked to the Gensini score. The association between lumbar disc lesions grading and coronary plaque burden was analysed by Spearman's correlation test. LDH patients with higher plaque burden (n = 56) were further divided into evolocumab treatment group (n = 28) and conventional treatment group (n = 28). Cox regression analysis were performed. Results: Patients with LDH had higher Gensini scores (P < 0.01) and triglyceride (TG) levels (P = 0.04), but HDL-C (P = 0.01) levels were lower. LDH was found to be an independent risk factor for higher Gensini scores (OR = 2.38, P < 0.01) by logistic analysis. The Spearman's correlation test suggested that the degree of lumbar disc lesions was related to the Gensini score and the level of blood lipid. Cox regression analysis showed that evolocumab treatment could significantly reduce the composite MACE events (cardiac death, nonfatal myocardial infarction, nonfatal stroke, and readmission due to angina) (HR = 0.26, P = 0.04) in higher coronary plaque burden patients. Conclusion: LDH is an independent risk factor for the higher coronary plaque burden. Evolocumab treatment significantly reduced the occurrence of cardiovascular events in LDH patients with higher plaque burden. Additionally, our data indicate that LDH is associated with increased blood lipid, which may contribute to the development of plaque burden.

Logic "AND Gate Circuit"-Based Gasdermin Protein Expressing Nanoplatform Induces Tumor-Specific Pyroptosis to Enhance Cancer Immunotherapy.

Pyroptosis mediated by gasdermin protein has shown great potential in cancer immunotherapies. However, the low expression of gasdermin proteins and the systemic toxicity of nonspecific pyroptosis limit its clinical application. Here, we designed a synthetic biology strategy to construct a tumor-specific pyroptosis-inducing nanoplatform M-CNP/Mn@pPHS, in which a pyroptosis-inducing plasmid (pPHS) was loaded onto a manganese (Mn)-doped calcium carbonate nanoparticle and wrapped in a tumor-derived cell membrane. M-CNP/Mn@pPHS showed an efficient tumor targeting ability. After its internalization by tumor cells, the degradation of M-CNP/Mn@pPHS in the acidic endosomal environment allowed the efficient endosomal escape of plasmid pPHS. To trigger tumor-specific pyroptosis, pPHS was designed according to the logic "AND gate circuit" strategy, with Hif-1α and Sox4 as two input signals and gasdermin D induced pyroptosis as output signal. Only in cells with high expression of Hif-1α and Sox4 simultaneously will the output signal gasdermin D be expressed. Since Hif-1α and Sox4 are both specifically expressed in tumor cells, M-CNP/Mn@pPHS induces the tumor-specific expression of gasdermin D and thus pyroptosis, triggering an efficient immune response with little systemic toxicity. The Mn2+ released from the nanoplatform further enhanced the antitumor immune response by stimulating the cGAS-STING pathway. Thus, M-CNP/Mn@pPHS efficiently inhibited tumor growth with 79.8% tumor regression in vivo. We demonstrate that this logic "AND gate circuit"-based gasdermin nanoplatform is a promising strategy for inducing tumor-specific pyroptosis with little systemic toxicity.

Reducing greenhouse gas intensity using a mixture of controlled-release urea and common urea combining suitable maize varieties in a summer maize system.

The one-time application of common urea blended with controlled-release urea (CRU) is considered effective for improving nitrogen use efficiency and grain yield and reducing the greenhouse gas emissions of summer maize in intensive agricultural systems. However, the trade-off between the economic and environmental performances of different blended fertilizer treatments for different maize varieties remains unclear. Therefore, a consecutive two-year field experiment was conducted in the North China Plain to study the effects of different ratios of CRU and common urea on the yield, nitrous oxide (N2O) emissions, yield-scaled total N2O emissions, greenhouse gas intensity (GHGI), and net ecosystem economic benefit (NEEB) in 2021 and 2022. Four N fertilizer treatments with equal rate at 180 kg N ha-1 were applied as N180U (all Urea), N180C1(1/3CRU), N180C2(2/3CRU), and N180C (all CRU), and two maize varieties (JNK728-yellow ripe variety and ZD958-green ripe variety) were used. The N180C1 and N180C2 treatments produced the highest grain yield in varieties JNK728 and ZD958 (9.4-11.5 t ha-1 and 9.0-11.0 t ha-1), respectively. Compared to the N180U treatment (conventional method), the N180C1 treatment reduced the GHGI (24.8 %-25.9 %) and increased the NEEB (33.1 %-33.4 %) in the JNK728 variety, whereas the N180C2 treatment reduced the GHGI (16.9 %-28.8 %) and increased the NEEB (27.2 %-48.1 %) in the ZD958 variety. The study concludes that a one-time application of blended nitrogen fertilizer in suitable varieties can minimize the GHGI and maximize the NEEB, which is an effective strategy for balancing yield and nitrogen efficiency in the summer maize system in the North China Plain.

Independent and interaction effects of prenatal exposure to high AQI and extreme Humidex on the risk of preterm birth: A large sample population study in northern China.

The combined effects of air pollution and extreme temperature on PTB remain unclear. To evaluate the independent effect and interaction effect of prenatal extreme exposure to air quality index (AQI) and Humidex, on PTB. Based on the National Health Care Data Platform of Shandong University, women who gave birth in 2019-2020 were selected for the study. First, the independent effects of AQI and Humidex on PTB were assessed by logistic regression model. Subsequently, the interaction effects of AQI and Humidex on PTB were estimated separately by calculation of the relative excess risk of interaction (RERI). A total of 34365 pregnant women were included and 1975 subjects were diagnosed with PTB. We observed a significant increase in the odds of PTB associated with maternal high AQI exposure, with an OR of 1.70 (95% CI: 1.59, 1.81). Similarly, extreme exposure to Humidex also demonstrated an elevated PTB odds, with a low Humidex OR of 2.48 (95% CI: 2.23, 2.76) and a high Humidex OR of 1.48 (95% CI: 1.31, 1.67). Finally, we observed an interaction between high AQI and extreme Humidex during the 1st trimester. Interaction effects were noted between high AQI and low Humidex throughout the entire trimester and the 2nd trimester. This study suggests that prenatal exposure to high AQI and extreme Humidex could increase the odds of PTB, with effects exhibiting the sensitivity window and a cumulative trend. Additionally, there is an interaction between AQI and Humidex.

Biomimetic-gasdermin-protein-expressing nanoplatform mediates tumor-specific pyroptosis for cancer immunotherapy.

Pyroptosis, mediated by gasdermin proteins, has shown excellent efficacy in facilitating cancer immunotherapy. The strategies commonly used to induce pyroptosis suffer from a lack of tissue specificity, resulting in the nonselective activation of pyroptosis and consequent systemic toxicity. Moreover, pyroptosis activation usually depends on caspase, which can induce inflammation and metabolic disorders. In this study, inspired by the tumor-specific expression of SRY-box transcription factor 4 (Sox4) and matrix metalloproteinase 2 (MMP2), we constructed a doubly regulated plasmid, pGMD, that expresses a biomimetic gasdermin D (GSDMD) protein to induce the caspase-independent pyroptosis of tumor cells. To deliver pGMD to tumor cells, we used a hyaluronic acid (HA)-shelled calcium carbonate nanoplatform, H-CNP@pGMD, which effectively degrades in the acidic endosomal environment, releasing pGMD into the cytoplasm of tumor cells. Upon the initiation of Sox4, biomimetic GSDMD was expressed and cleaved by MMP2 to induce tumor-cell-specific pyroptosis. H-CNP@pGMD effectively inhibited tumor growth and induced strong immune memory effects, preventing tumor recurrence. We demonstrate that H-CNP@pGMD-induced biomimetic GSDMD expression and tumor-specific pyroptosis provide a novel approach to boost cancer immunotherapy.

Gate-Controlled Neuromorphic Functional Transition in an Electrochemical Graphene Transistor.

Neuromorphic devices have attracted significant attention as potential building blocks for the next generation of computing technologies owing to their ability to emulate the functionalities of biological nervous systems. The essential components in artificial neural networks such as synapses and neurons are predominantly implemented by dedicated devices with specific functionalities. In this work, we present a gate-controlled transition of neuromorphic functions between artificial neurons and synapses in monolayer graphene transistors that can be employed as memtransistors or synaptic transistors as required. By harnessing the reliability of reversible electrochemical reactions between carbon atoms and hydrogen ions, we can effectively manipulate the electric conductivity of graphene transistors, resulting in a high on/off resistance ratio, a well-defined set/reset voltage, and a prolonged retention time. Overall, the on-demand switching of neuromorphic functions in a single graphene transistor provides a promising opportunity for developing adaptive neural networks for the upcoming era of artificial intelligence and machine learning.

The co-inoculation of Trichoderma viridis and Bacillus subtilis improved the aerobic composting efficiency and degradation of lignocellulose.

The aim of this study was to reveal the mechanism by which co-inoculation with both Trichoderma viridis and Bacillus subtilis improved the efficiency of composting and degradation of lignocellulose in agricultural waste. The results showed that co-inoculation with Trichoderma and Bacillus increased abundance of Bacteroidota to promote the maturation 7 days in advance. Galbibacter may be a potential marker of co-inoculation composting efficiency compost. The compost became dark brown, odorless, and had a carbon to nitrogen ratio of 16.40 and a pH of 8.2. Moreover, Actinobacteriota and Firmicutes still dominated the degradation of lignocellulose following inoculation with Trichoderma or Bacillus 35 days after composting. Bacterial function prediction analysis showed that carbohydrate metabolism was the primary metabolic pathway. In conclusion, co-inoculation with Trichoderma and Bacillus shortened the composting cycle and accelerated the degradation of lignocellulose. These findings provide new strategies for the efficient use of agricultural waste to produce organic fertilizers.

Microbial metabolic flexibility guarantees function resilience in response to starvation disturbance.

Starvation disturbance due to nutrient limitation is a common problem in bioreactors. However, an understanding of how microbial systems respond to starvation remains in its infancy. Here the metabolic response mechanism of a biofilm community to starvation was investigated using a well-controlled gaseous toluene treatment biofilter through interruption of its operation. It was found that metabolic characteristics showed significant differences before and after starvation. The dominant carbon source utilization type shifted from amino acids and carboxylic acids to esters and carbohydrates after starvation, which is more conducive to improving energy production. Metagenomic sequencing analysis supported that the changes in the dominant metabolic substrate, enhanced metabolic stability, and flexibility in the mode of energy metabolism could be the main ways to guarantee functional resilience in ecosystems after starvation. The results highlight the microbial metabolic response to starvation, which would be beneficial to the understanding of functional resilience and bioreactor stability.

Time-Lagged Functional Ultrasound for Multi-Parametric Cerebral Hemodynamic Imaging.

We introduce an ultrasound speckle decorrelation-based time-lagged functional ultrasound technique (tl-fUS) for the quantification of the relative changes in cerebral blood flow speed (rCBF [Formula: see text]), cerebral blood volume (rCBV) and cerebral blood flow (rCBF) during functional stimulations. Numerical simulations, phantom validations, and in vivo mouse brain experiments were performed to test the capability of tl-fUS to parse out and quantify the ratio change of these hemodynamic parameters. The blood volume change was found to be more prominent in arterioles compared to venules and the peak blood flow changes were around 2.5 times the peak blood volume change during brain activation, agreeing with previous observations in the literature. The tl-fUS shows the ability of distinguishing the relative changes of rCBFspeed, rCBV, and rCBF, which can inform specific physiological interpretations of the fUS measurements.

Inversion diffuse attenuation coefficient of photosynthetically active radiation based on deep learning.

Accurate estimation of the diffuse attenuation coefficient of photosynthetically active radiation, Kd(PAR), is critical for understanding and modeling key physical, chemical, and biological processes in waters. In this study, a deep learning model (DLKPAR) was developed for remotely estimating Kd(PAR). Compared to the traditional empirical algorithms and semi-analytical algorithm, DLKPAR demonstrated an improvement in the model's stability and accuracy. By using in situ NOMAD data to evaluate the model's performance, DLKPAR had lower root mean square difference (RMSD; 0.028 vs. 0.030-0.048 m-1) and mean absolute relative difference (MARD; 0.14 vs. 0.17-0.25) and higher R2 (0.94 vs. 0.82-0.94). The statistical results of the matchup NOMAD and Argo data to the MODIS also indicated DLKPAR improves the inversion accuracy of Kd(PAR) and could be applied to remotely estimate Kd(PAR) in the global oceans. Therefore, we anticipate that DLKPAR could yield reliable Kd(PAR) values from ocean color remote sensing, providing an accurate estimation of visible light attenuation in the upper ocean and facilitating biogeochemical cycle research.

Chinese Materia Medica in Treating Depression: The Role of Intestinal Microenvironment.

Depression is a highly heterogeneous mental illness. Drug treatment is currently the main therapeutic strategy used in the clinic, but its efficacy is limited by the modulation of a single target, slow onset, and side effects. The gut-brain axis is of increasing interest because intestinal microenvironment disorders increase susceptibility to depression. In turn, depression affects intestinal microenvironment homeostasis by altering intestinal tissue structure, flora abundance and metabolism, hormone secretion, neurotransmitter transmission, and immune balance. Depression falls into the category of "stagnation syndrome" according to Traditional Chinese Medicine (TCM), which further specifies that "the heart governs the spirit and is exterior-interior with the small intestine". However, the exact mechanisms of the means by which the disordered intestinal microenvironment affects depression are still unclear. Here, we present an overview of how the Chinese materia medica (CMM) protects against depression by repairing intestinal microenvironment homeostasis. We review the past five years of research progress in classical antidepressant TCM formulae and single CMMs on regulating the intestinal microenvironment for the treatment of depression. We then analyze and clarify the multitarget functions of CMM in repairing intestinal homeostasis and aim to provide a new theoretical basis for CMM clinical application in the treatment of depression.

Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy.

Our objective was to evaluate the long-term prognostic value of high-sensitivity cardiac troponin-I (hs-cTn-I) in idiopathic dilated cardiomyopathy (DCM). First, patients were divided into an end-event group (n = 55) and a non-end-event group (n = 67). Then, patients were included in the subgroup analysis to compare the diagnostic value of brain natriuretic peptide (BNP) and hs-cTn-I in different populations. hs-cTn-I and BNP concentrations were higher in the end-event group. The Cox regression analysis indicated that high hs-cTn-I was a risk factor for poor long-term prognosis. Receiver operating characteristic analysis showed that the area under the curve (AUC) for hs-cTn-I to predict end events was 0.751, and the AUC for BNP was 0.742. The correlation analysis suggested that hs-cTn-I was related to the percentage change in left ventricular internal diameter at end-diastolic and left ventricular ejection fraction. Subgroup analysis showed that compared with BNP, hs-cTn-I was more suitable for predicting end events in patients with preserved renal function (AUC: 0.853 vs 0.712, P = 0.04). In conclusion, hs-cTn-I is a potential biomarker for evaluating long-term prognosis in idiopathic DCM, and its predictive value is higher than that of BNP in patients with preserved renal function.

Real-time observation of magnetization and magnon dynamics in a two-dimensional topological antiferromagnet MnBi2Te4.

Atomically thin van der Waals magnetic materials have not only provided a fertile playground to explore basic physics in the two-dimensional (2D) limit but also created vast opportunities for novel ultrafast functional devices. Here we systematically investigate ultrafast magnetization dynamics and spin wave dynamics in few-layer topological antiferromagnetic MnBi2Te4 crystals as a function of layer number, temperature, and magnetic field. We find laser-induced (de)magnetization processes can be used to accurately track the distinct magnetic states in different magnetic field regimes, including showing clear odd-even layer number effects. In addition, strongly field-dependent AFM magnon modes with tens of gigahertz frequencies are optically generated and directly observed in the time domain. Remarkably, we find that magnetization and magnon dynamics can be observed in not only the time-resolved magneto-optical Kerr effect but also the time resolved reflectivity, indicating strong correlation between the magnetic state and electronic structure. These measurements present the first comprehensive overview of ultrafast spin dynamics in this novel 2D antiferromagnet, paving the way for potential applications in 2D antiferromagnetic spintronics and magnonics as well as further studies of ultrafast control of both magnetization and topological quantum states.

Engineering a Pseudomonas putida as living quorum quencher for biofilm formation inhibition, benzenes degradation, and environmental risk evaluation.

Bacterial communication interruption based on quorum quenching (QQ) has been proven its potential in biofilm formation inhibition and biofouling control. However, it would be more satisfying if QQ could be combined with the efficient degradation of contaminants in environmental engineering. In this study, we engineered a biofilm of Pseudomonas putida through introducing a QQ synthetic gene, which achieved both biofilm formation inhibition and efficient degradation of benzene series in wastewater. The aiiO gene introduced into the P. putida by heat shock method was highly expressed to produce QQ enzyme to degrade AHL-based signal molecules. The addition of this engineered P. putida reduced the AHLs concentration, quorum sensing gene expression, and connections of the microbial community network in activated sludge and therefore inhibited the biofilm formation. Meanwhile, the sodium benzoate degradation assay indicated an enhanced benzene series removal ability of the engineering bacteria on activated sludge. Besides, we also demonstrated a controllable environmental risk of this engineered bacteria through monitoring its abundance and horizontal gene transfer test. Overall, the results of this study suggest an alternative strategy to solve multiple environmental problems through genetic engineering means and provide support for the application of engineered bacteria in environmental biotechnology.

Construction of 1,4-Dihydropyridines: The Evolution of C4 Source.

The field of cascade cyclization for the construction of 1,4-dihydropyridines (1,4-DHPs) has been continuously expanding during the last decades because of their broad-spectrum biological and synthetic importance. To date, many methods have been developed, mainly including the Hantzsch reaction, Hantzsch-like reaction and newly developed cascade cyclization, in which various synthons have been successively developed as C4 sources of 1,4-DHPs. This review presents the cascade cyclization synthesis strategy for the construction of 1,4-DHPs according to various C4 sources from carbonyl compounds, alkenyl fragments, alcohols, aliphatic amines, glycines and other C4 sources.

Suppression of cytokine release syndrome during CAR-T-cell therapy via a subcutaneously injected interleukin-6-adsorbing hydrogel.

The infusion of chimaeric antigen receptor (CAR) T cells can trigger the release of life-threatening supraphysiological levels of pro-inflammatory cytokines. However, uncertainty regarding the timing and severity of such cytokine release syndrome (CRS) demands careful monitoring of the conditions required for the administration of neutralizing antibodies. Here we show that a temperature-sensitive hydrogel conjugated with antibodies for the pro-inflammatory cytokine interleukin-6 (IL-6) and subcutaneously injected before the infusion of CAR-T cells substantially reduces the levels of IL-6 during CRS while maintaining the therapy's antitumour efficacy. In immunodeficient mice and in mice with transplanted human haematopoietic stem cells, the subcutaneous IL-6-adsorbing hydrogel largely suppressed CAR-T-cell-induced CRS, substantially improving the animals' survival and alleviating their levels of fever, hypotension and weight loss relative to the administration of free IL-6 antibodies. The implanted hydrogel, which can be easily removed with a syringe following a cooling-induced gel-sol transition, may allow for a shift in the management of CRS, from monitoring to prevention.

Near-Infrared II Semiconducting Polymer Dots: Chain Packing Modulation and High-Contrast Vascular Imaging in Deep Tissues.

Fluorescence imaging in the second near-infrared (NIR-II) window has attracted considerable interest in investigations of vascular structure and angiogenesis, providing valuable information for the precise diagnosis of early stage diseases. However, it remains challenging to image small blood vessels in deep tissues because of the strong photon scattering and low fluorescence brightness of the fluorophores. Here, we describe our combined efforts in both fluorescent probe design and image algorithm development for high-contrast vascular imaging in deep turbid tissues such as mouse and rat brains with intact skull. First, we use a polymer blending strategy to modulate the chain packing behavior of the large, rigid, NIR-II semiconducting polymers to produce compact and bright polymer dots (Pdots), a prerequisite for in vivo fluorescence imaging of small blood vessels. We further developed a robust Hessian matrix method to enhance the image contrast of vascular structures, particularly the small and weakly fluorescent vessels. The enhanced vascular images obtained in whole-body mouse imaging exhibit more than an order of magnitude improvement in the signal-to-background ratio (SBR) as compared to the original images. Taking advantage of the bright Pdots and Hessian matrix method, we finally performed through-skull NIR-II fluorescence imaging and obtained a high-contrast cerebral vasculature in both mouse and rat models bearing brain tumors. This study in Pdot probe development and imaging algorithm enhancement provides a promising approach for NIR-II fluorescence vascular imaging of deep turbid tissues.