NIR-II nanoprobes for investigating the glymphatic system function under anesthesia and stroke injury.

The glymphatic system plays an important role in the transportation of cerebrospinal fluid (CSF) and the clearance of metabolite waste in brain. However, current imaging modalities for studying the glymphatic system are limited. Herein, we apply NIR-II nanoprobes with non-invasive and high-contrast advantages to comprehensively explore the function of glymphatic system in mice under anesthesia and cerebral ischemia-reperfusion injury conditions. Our results show that the supplement drug dexmedetomidine (Dex) enhances CSF influx in the brain, decreases its outflow to mandibular lymph nodes, and leads to significant differences in CSF accumulation pattern in the spine compared to isoflurane (ISO) alone, while both ISO and Dex do not affect the clearance of tracer-filled CSF into blood circulation. Notably, we confirm the compromised glymphatic function after cerebral ischemia-reperfusion injury, leading to impaired glymphatic influx and reduced glymphatic efflux. This technique has great potential to elucidate the underlying mechanisms between the glymphatic system and central nervous system diseases.

[Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia].

OBJECTIVE: To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. METHODS: 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. RESULTS: The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. CONCLUSION: The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.

Genetic Insights into the Association and Causality Between Blood Metabolites and Alzheimer's Disease.

Background: Alzheimer's disease (AD) is an increasing public health concern with the aging of the global population. Understanding the genetic correlation and potential causal relationships between blood metabolites and AD may provide important insights into the metabolic dysregulation underlying this neurodegenerative disorder. Objective: The aim of this study was to investigate the causal relationship between blood metabolites and AD using Mendelian randomization (MR) analysis. Methods: Association data were obtained from three large-scale genome-wide association studies of 486 blood metabolites (N = 7,824), AD (71,880 cases and 383,378 controls), early-onset AD (N = 303,760), and late-onset AD (N = 307,112). Causal associations between blood metabolites and AD were assessed using inverse variance weighting (IVW), MR-Egger, and weighted median methods. Bidirectional two-sample MR analysis was used to identify causal blood metabolites. MR-PRESSO, MR-Egger, and Cochran-Q were used to quantify instrumental variable heterogeneity and horizontal pleiotropy. Results: Using MR and sensitivity analysis, we identified 40 blood metabolites with potential causal associations with AD. After applying false discovery rate (FDR) correction, two metabolites, gamma-glutamylphenylalanine (OR = 1.15, 95% CI: 1.06-1.24, p = 3.88×10-4, q = 0.09) and X-11317 (OR = 1.16, 95% CI: 1.08-1.26, p = 1.14×10-4, q = 0.05), retained significant associations with AD. Reverse MR analysis indicated no significant causal effect of AD on blood metabolites. No significant instrumental variable heterogeneity or horizontal pleiotropy was found. Conclusions: This two-sample MR study provides compelling evidence for a potential causal relationship between blood metabolic dysregulation and susceptibility to AD. Further investigation of the biological relevance of the identified metabolites to AD and additional supporting evidence is warranted.

Magnetic propelled hydrogel microrobots for actively enhancing the efficiency of lycorine hydrochloride to suppress colorectal cancer.

Research and development in the field of micro/nano-robots have made significant progress in the past, especially in the field of clinical medicine, where further research may lead to many revolutionary achievements. Through the research and experiment of microrobots, a controllable drug delivery system will be realized, which will solve many problems in drug treatment. In this work, we design and study the ability of magnetic-driven hydrogel microrobots to carry Lycorine hydrochloride (LH) to inhibit colorectal cancer (CRC) cells. We have successfully designed a magnetic field driven, biocompatible drug carrying hydrogel microsphere robot with Fe3O4 particles inside, which can achieve magnetic field response, and confirmed that it can transport drug through fluorescence microscope. We have successfully demonstrated the motion mode of hydrogel microrobots driven by a rotating external magnetic field. This driving method allows the microrobots to move in a precise and controllable manner, providing tremendous potential for their use in various applications. Finally, we selected drug LH and loaded it into the hydrogel microrobot for a series of experiments. LH significantly inhibited CRC cells proliferation in a dose- and time-dependent manner. LH inhibited the proliferation, mobility of CRC cells and induced apoptosis. This delivery system can significantly improve the therapeutic effect of drugs on tumors.

Effects of Low Protein Diet on Production Performance and Intestinal Microbial Composition in Pigs.

In order to study the effects of a low protein diet on the production performance and intestinal microbiota composition of Hexi pigs, twenty-seven Hexi pigs with an initial body weight of 60.50 ± 2.50 kg were randomly divided into three groups (control group (CG), group 1 (G1), and group 2 (G2)) and participated in a 60-day finishing trial. The CG was fed a normal protein level diet with a protein level of 16.0%, and G1 and G2 were fed a low protein level diet with protein levels of 14.0% and 12.0%, respectively. The results showed that the low protein level diet had no significant effect on the production performance of Hexi pigs, compared with the CG, the slaughter rate of G1 and G2 increased by 2.49% (p > 0.05) and 6.18% (p > 0.05), the shear force decreased by 2.43% (p > 0.05) and 15.57% (p > 0.05), the cooking loss decreased by 24.02% (p < 0.05) and 21.09% (p > 0.05), and the cooking percentage increased by 13.20% (p > 0.05) and 11.59% (p > 0.05). From 45 min to 24 h and 48 h after slaughter, each group of pH decreased by 1.02, 0.66, and 0.42. For muscle flesh color, the lightness (L) increased by 13.31% (p > 0.05) and 18.01% (p > 0.05) in G1 and G2 and the yellowness (b) increased by 7.72% (p > 0.05) and 13.06% (p > 0.05). A low protein level diet can improve the intestinal flora richness and diversity of growing and finishing pigs. In the jejunum, the ACE index (899.95), Simpson index (0.90), and Shannon (4.75) index were higher in G1 than in the other groups, but the Chao1 index (949.92) was higher in G2 than in the remaining two groups. Proteobacteria, Actinobacteria, Euryarchaeota, and Verrucomicrobia were significantly higher in G1 than in the CG. The relative abundances of Lactobacillus, Terrisporobacter, and Megasphaera in G1 was significantly higher than in the CG (p < 0.05). In the cecum, the ACE index (900.93), Chao1 index (879.10), Simpson index (0.94), and Shannon (5.70) index were higher in G1 than in the remaining groups. The Spirochaetes in G2 were significantly higher than in the other groups, but the Verrucomicrobia was significantly lower than in the other groups. The relative abundances of Lactobacillus were higher in G1 and G2 than in the CG (p > 0.05). The relative abundances of unidentified_Clostridiales and Terrisporobacter in G2 were significantly lower than in the CG (p < 0.05). The relative abundance of Turicibacter in G1 was significantly lower than in the CG (p < 0.05). The relative abundances of other bacterial genera in G1 and G2 were increased by 30.81% (p > 0.05) and 17.98% (p > 0.05).

BK-SWMM flood simulation framework is being proposed for urban storm flood modeling based on uncertainty parameter crowdsourcing data from a single functional region.

In recent years, urban flood disasters caused by sudden heavy rains have become increasingly severe, posing a serious threat to urban public infrastructure and the life and property safety of residents. Rapid simulation and prediction of urban rain-flood events can provide timely decision-making reference for urban flood control and disaster reduction. The complex and arduous calibration process of urban rain-flood models has been identified as a major obstacle affecting the efficiency and accuracy of simulation and prediction. This study proposes a multi-scale urban rain-flood model rapid construction method framework, BK-SWMM, focusing on urban rain-flood model parameters and based on the basic architecture of Storm Water Management Model (SWMM). The framework comprises two main components: 1) constructing a SWMM uncertainty parameter sample crowdsourcing dataset and coupling Bayesian Information Criterion (BIC) and K-means clustering machine learning algorithm to discover clustering patterns of SWMM model uncertainty parameters in urban functional areas; 2) coupling BIC and K-means with SWMM model to form BK-SWMM flood simulation framework. The applicability of the proposed framework is validated by modeling three different spatial scales in the study regions based on observed rainfall-runoff data. The research findings indicate that the distribution pattern of uncertainty parameters, such as depression storage, surface Manning coefficient, infiltration rate, and attenuation coefficient. The distribution patterns of these seven parameters in urban functional zones indicate that the values are highest in the Industrial and Commercial Areas (ICA), followed by Residential Areas (RA), and lowest in Public Areas (PA). All three spatial scales' REQ, NSEQ, and RD2 indices were superior to the SWMM and less than 10%, greater than 0.80, and greater than 0.85, respectively. However, when the study area's geographical scale expands, the simulation's accuracy will decline. Further research is required on the scale dependency of urban storm flood models.

First principles prediction of two-dimensional Janus STiXY2 (X = Si, Ge; Y = N, P, As) materials.

Since the successful experimental synthesis of MoSi2N4, the "MA2Z4 family" has attracted the interest of researchers from many fields due to its excellent physical and chemical properties. In this work, we propose a novel two-dimensional Janus STiXY2 (X = Si, Ge; Y = N, P, As) monolayer using first principles. Under biaxial strain and an applied electric field, we investigate the controllable electronic properties of Janus STiXY2 (X = Si, Ge; Y = N, P, As) structures. Our predictions demonstrate that the 2D STiXY2 materials are structurally and dynamically stable. Using the HSE functional, we show that these 2D STiXY2 materials are indirect semiconductors with band gaps of 0.99, 1.142, 0.834, 1.322, 0.735, and 0.215 eV, respectively. Additionally, we found that, except for the STiXAs2 (X = Si, Ge) monolayer, the influence of biaxial strain on electronic characteristics is significantly greater than that of the applied electric field. Finally, we calculated the carrier mobilities of these Janus structures and found that the STiGeP2 monolayer has the highest electron carrier mobility in the x-direction with 8175.66 cm2 s-1 V-1, while the STiGeAs2 monolayer has the highest electron carrier mobility in the y-direction, 2897.94 cm2 s-1 V-1. They are all larger than those of the experimentally synthesized MoS2 (∼200 cm2 s-1 V-1). The results may provide insights for the study of novel Janus monolayers with potential application in electronic devices.

Lymphomatoid granulomatosis with the central nervous system involvement as the main manifestation: a case report.

BACKGROUND: Lymphomatoid granulomatosis (LyG) is a rare extralymphatic lymphoproliferative disease characterized by lymphocytic invasion into vascular walls and damage to blood vessels. The lungs are affected in 90% of LyG cases, followed by the skin, central nervous system (CNS), kidneys and liver. CASE PRESENTATION: Here we report a case of a young woman with LyG, with CNS involvement as the initial clinical manifestation. Computer tomography (CT) scans showed multiple nodular, patchy and flocculent high-density shadows in both lungs without mediastinal lymph node enlargement. Magnetic resonance imaging (MRI) scans showed multiple abnormal signal intensities in the right cerebellar hemisphere, frontal, parietal and temporal lobes, and dorsal brainstem, which became patchy and annular after enhancement. The post-operative pathological analysis of lesion samples confirmed the diagnosis of grade II LyG. CONCLUSIONS: LyG should be concerned in young adults showing multiple radiological brain and lung lesions. Resection and postoperative medication of steroid hormones and IFN-α may be effective in the treatment of LyG.

Two-dimensional Pd3(AsSe4)2 as a photocatalyst for the solar-driven oxygen evolution reaction: a first-principles study.

The relationship between the structure and properties of materials is the core of material research. Bulk Pd3(PS4)2 materials have been successfully synthesized in the field of three-dimensional materials. After that, various studies on two-dimensional layered materials were conducted. Inspired by these successes, this work used density functional theory based on first principles to explore similar two-dimensional Pd3(AsX4)2, where X is S, Se, or Te belonging to the same group. Our findings demonstrate that the Pd3(AsS4)2 and Pd3(AsSe4)2 monolayers, with HSE06 band gaps of 2.37 and 1.36 eV, respectively, are indirect semiconductors. Additionally, their carrier mobilities [523.23 cm2 s-1 V-1 and 440.6 cm2 s-1 V-1] are also proved to be superior to MoS2 [∼200 cm2 s-1 V-1]. The optical calculations indicate that the Pd3(AsSe4)2 monolayer yields suitable valence band edge positions for the visible-light-driven water splitting reactions. More interestingly, at a low applied voltage of 0.14 V, Pd3(AsSe4)2 exhibits outstanding oxygen evolution reaction performance. In this study, the possible mechanism for the ability of Pd3(AsSe4)2 monolayer to promote photocatalysis and oxygen evolution was explained, which may pave the way for the practical design of further solar-driven high-quality water splitting photocatalysis.

Electronic Properties and Electrocatalytic Water Splitting Activity for Precious-Metal-Adsorbed Silicene with Nonmetal Doping.

Since nonmetal (NM)-doped two-dimensional (2D) materials can effectively modulate their physical properties and chemical activities, they have received a lot of attention from researchers. Therefore, the stability, electronic properties, and electrocatalytic water splitting activity of precious-metal (PM)-adsorbed silicene doped with two NM atoms are investigated based on density functional theory (DFT) in this paper. The results show that NM doping can effectively improve the stability of PM-adsorbed silicene and exhibit rich electronic properties. Meanwhile, by comparing the free energies of the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) intermediates of 15 more stable NM-doped systems, it can be concluded that the electrocatalytic water splitting activity of the NM-doped systems is more influenced by the temperature. Moreover, the Si-S2-Ir-doped system exhibits good HER performance when the temperature is 300 K, while the Si-N2-Pt-doped system shows excellent OER activity. Our theoretical study shows that NM doping can effectively promote the stability and electrocatalytic water splitting of PM-adsorbed silicene, which can help in the application of silicene in electrocatalytic water splitting.

Different Lewis Acid Promotor-Steered Highly Regioselective Phosphorylation of Tertiary Enamides.

Different Lewis acid promotor-steered highly regioselective phosphorylation of tertiary enamides with diverse H-phosphonates or H-phosphine oxides was developed. Under the catalysis of iron salt, the phosphonyl group was introduced into the α-position of tertiary enamides, affording various α-phosphorylated amides in high efficiency. On the other hand, the ß-phosphorylated tertiary enamides were efficiently obtained as the products in the presence of manganese(III) acetylacetonate.

Bioorthogonal DOPA-NGF activated tissue engineering microunits for recovery from traumatic brain injury by microenvironment regulation.

Stem cell treatment is vital for recovery from traumatic brain injury (TBI). However, severe TBI usually leads to excessive inflammation and neuroinhibitory factors in the injured brain, resulting in poor neural cell survival and uncontrolled formation of glial scars. In this study, a bioorthogonal microenvironment was constructed on biodegradable poly(lactide-co-glycolide) (PLGA) microcarriers through immobilization of mussel-inspired bioorthogonal 3,4-dihydroxyphenylalanine-containing recombinant nerve growth factor (DOPA-NGF) and human umbilical cord mesenchymal stem cells (hUMSCs) for minimally invasive therapy of TBI. Cell culture and RNA-seq analysis revealed enhanced extracellular matrix (ECM) secretion and viability of hUMSCs on PLGA microcarriers compared to 2D culture. Immobilized DOPA-NGF further promoted adhesion, proliferation, and gene expression in RSC96 neurotrophic cells and hUMSCs. Specifically, the neurotrophin receptor of NT-3 (NTRK3) in hUMSCs was activated by DOPA-NGF, leading to MYC transcription and paracrine enhancement to build an adjustable biomimetic microenvironment. After transplantation of microunits in animal models, the motor and learning-memory ability of TBI mice were improved through rollbacks of overactivated inflammatory reaction regulation, neuronal death, and glial scar formation after injury. This was attributed to the paracrine enhancement of hUMSCs activated by the DOPA-NGF. Our study provides a neural regenerative microenvironment-based therapeutic strategy to advance the effects of transplanted hUMSCs in cell-based regenerative medicine for TBI therapy. STATEMENT OF SIGNIFICANCE: Extensive studies have demonstrated the importance of the microenvironment for posttraumatic brain injury recovery. However, an efficient method that can mimic the neural regenerative microenvironment to strengthen stem cell therapy and brain injury recovery is still absent. In this study, the minimally invasive transplantation of DOPA-NGF immobilized biodegradable microcarriers with mesenchymal stem cells was found to be an effective method for regeneration of injured brain. Moreover, transcriptome analysis revealed that neurotrophin receptor of NT-3 (NTRK3) was activated by DOPA-NGF for MYC transcription and paracrine enhancement to build a kind of adjustable biomimetic microenvironment for brain injury therapy. This study provides a neural regenerative microenvironment-based therapeutic strategy to advance the transplanted hUMSCs in cell-based regenerative medicine for neural recovery.

Manganese(III)-promoted highly stereoselective phosphorylation of acyclic tertiary enamides to synthesize E-selective ß-phosphoryl enamides.

A concise manganese(III)-promoted stereoselective ß-phosphorylation of acyclic tertiary enamides and diverse H-phosphine oxides was achieved. This reaction proceeds with absolute E-selectivity in contrast to Z-selectivity obtained in other previous works and affords various E-selective ß-phosphorylated tertiary enamides in high efficiency. To the best of our knowledge, this is the first case of E-selective ß-phosphorylation of tertiary enamides through C-H functionalization. In addition, the method features broad substrate scope, good functional group compatibility and efficient scale-up.

Amphiphilic shell nanomagnetic adsorbents for selective and highly efficient capture of low-density lipoprotein from hyperlipidaemia serum.

Removal of low-density lipoprotein (LDL) from hyperlipemia patients' blood represents an effective approach to prevent the progression of atherosclerotic cardiovascular disease. Based on the LDL structural characteristics and intermolecular interactions, a tailored nano-adsorbent (Fe3O4@SiO2@PAA-PE) was prepared aimed at the removal of LDL from hyperlipemia serum with high selectivity. The core-shell structured magnetic nanoparticles were embedded in an amphiphilic layer composed of hydrophilic poly(acrylic acid) and lipophilic phospholipids to provide multifunctional binding for LDL particles. The results of dynamic light scattering, water contact angle and zeta-potential measurements, thermal gravimetric analysis, and X-ray photoelectron spectroscopy together with Fourier transform infrared spectroscopy confirmed the core-shell structured nanoparticles bearing amphiphilic poly acrylic acid and phospholipid molecules. Because of the superior electronegativity of the functional layer, the nano-adsorbent demonstrated favorable adsorption selectivity against high-density lipoprotein, which possesses a similar structure to LDL but has a cardio-protective function in the human body. The respective adsorption capacity of Fe3O4@SiO2@PAA-PE towards LDL, total cholesterol and triglycerides reached up to 6.26 mg g-1, 8.41 mg g-1 and 9.19 mg g-1, which was 7.03, 9.45 and 10.32 times that towards HDL (0.89 mg g-1). The kinetic and isothermal studies revealed that multiple interactions containing both physical and chemical adsorption occurred in the binding procedure between LDL and Fe3O4@SiO2@PAA-PE, and chemical adsorption may play a more predominant role in LDL adsorption. The nano-adsorbent also had negligible effects on blood cells, and possessed satisfactory recyclability, low cytotoxicity and hemolysis ratios, indicating its good application prospects as a hemoperfusion adsorbent in the treatment of hyperlipidaemia.

A novel adoptive synthetic TCR and antigen receptor (STAR) T-Cell therapy for B-Cell acute lymphoblastic leukemia.

We developed a T-cell-receptor (TCR) complex-based chimeric antigen receptor (CAR) named Synthetic TCR and Antigen Receptor (STAR). Here, we report pre-clinical and phase I clinical trial data (NCT03953599) of this T-cell therapy for refractory and relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL) patients. STAR consists of two protein modules each containing an antibody light or heavy chain variable region and TCR α or ß chain constant region fused to the co-stimulatory domain of OX40. T-cells were transduced with a STAR-OX40 lentiviral vector. A leukemia xenograft mouse model was used to assess the STAR/STAR-OX40 T cell antitumor activity. Eighteen patients with R/R B-ALL were enrolled into the clinical trial. In a xenograft mouse model, STAR-T-cells exhibited superior tumor-specific cytotoxicity compared with conventional CAR-T cells. Incorporating OX40 into STAR further improved the proliferation and persistence of tumor-targeting T-cells. In our clinical trial, 100% of patients achieved complete remission 4 weeks post-STAR-OX40 T-cell infusion and 16/18 (88.9%) patients pursued consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twelve of 16 patients (75%) remained leukemia-free after a median follow-up of 545 (433-665) days. The two patients without consolidative allo-HSCT relapsed on Day 58 and Day 186. Mild cytokine release syndrome occurred in 10/18 (55.6%) patients, and 2 patients experienced grade III neurotoxicity. Our preclinical studies demonstrate super anti-tumor potency of STAR-OX40 T-cells compared with conventional CAR-T cells. The first-in-human clinical trial shows that STAR-OX40 T-cells are tolerable and an effective therapeutic platform for treating R/R B-ALL.

[Overexpression of circ_LARP4 inhibits the proliferation and migration of MCF-7 human breast cancer cells and its mechanism].

Objective To investigate the effect of overexpression of circRNA La-associated protein 4 (circ_LARP4) on malignant biological behaviors of MCF-7 breast cancer cells. Methods MCF-7 cells were transfected with circ_LARP4 plasmid pcDNA-circ_LARP4, and the expression of circ_LARP4 was detected by real-time quantitative PCR(qRT-PCR). After circ_LARP4 overexpression, CCK-8 assay was used to detect the proliferation of MCF-7 cells, and mRNAs of ki67, p21, inducible nitric oxide synthase (iNOS) and interleukin-1ß (IL-1ß) were detected by qRT-PCR. The bullet volume of tumor stem cells was observed under microscope, and the number of invaded cells was detected by TranswellTM assay. The expressions of octamer binding transcription factor 4(OCT4), SRY-related high-mobility-group box gene 2 (SOX2), vascular endothelial growth factor (VEGF), epithelial cadherin (E-cadherin) and neural cadherin (N-cadherin) were detected by Western blot. The levels of iNOS and IL-1ß in the supernatant of MCF-7 cells were detected by ELISA. Results Compared with the control group, circ_LARP4 overexpression group showed an upregulation in the expression of circ_LARP4, decreased cell proliferation, and down-regulated expression of ki67. It also reported the up-regulated expression of p21, smaller tumor stem cell bullet size, and decreased the expression of OCT4 and SOX2, together with the decreased number of invaded cells, decreased expression of VEGF and N-cadherin, increased expression of E-cadherin, and decreased levels of iNOS and IL-1ß. Conclusion Overexpression of circ_LARP4 inhibits the proliferation, invasion and stem cell-like characteristics of MCF-7 breast cancer cells, and down-regulates the levels of iNOS and IL-1ß.

Enzyme-responsive strategy as a prospective cue to construct intelligent biomaterials for disease diagnosis and therapy.

Stimulus-responsive materials have been widely studied and applied in biomedical fields. Under the stimulation of enzymes, enzyme-responsive materials (ERMs) can be triggered to change their structures, properties and functions. Herein, natural enzymes act as the endogenous trigger. Owing to the specificity of natural enzymes, ERMs can exert functions in the specific tissues containing these enzymes, while remaining inert in other tissues. This is beneficial for modulating the therapy efficacy and alleviating systemic or local toxicities in vivo when ERMs are used to deliver therapeutic molecules. This article focuses on introducing enzyme-responsive strategies, ERMs and their applications in cancer and cardiovascular disease diagnosis, therapy and theranostics. Enzyme-responsive strategies provide a promising research cue to construct intelligent biomaterials for disease treatment and diagnosis.

Modulation of lymphatic transport in the central nervous system.

Over the past decade, repeated studies demonstrated that the vertebrate brain had a specialized lymphatic transport pathway, which overturned the traditional concept of central nervous system (CNS) immune privilege. Despite the lack of lymphatic vessels, the glymphatic system and the meningeal lymphatic vessels provide a unique pathway for solutes transport and metabolites clearance in the brain. Sleep, circadian rhythm, arterial pulsation, and other physiological factors modulate this specialized lymphatic drainage pathway. It has also changed significantly under pathological conditions. These modulatory mechanisms may arise critical targets for the therapeutic of CNS disorders. This review highlights the latest research progress on the modulation of lymphatic transport in the CNS under physiological and pathological conditions. Furthermore, we examined the possible upstream and downstream relation networks between these regulatory mechanisms.