A novel peptide-drug conjugate for glioma-targeted drug delivery.

The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel "Y"-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery.

Cation-induced Ti3C2Tx MXene@melamine sponge aerogels with large layer spacing and high strength for high-performance supercapacitors.

The self-assembled aerogels are considered as an efficient strategy to address the aggregation and restacking of Ti3C2Tx MXene nanosheets for high-performance supercapacitors. However, the low mechanical strength of the MXene aerogel results in the structural collapse of the self-standing supercapacitor electrode materials. Herein, a low-cost melamine sponge (MS) absorbed different cations (H+, K+, Mg2+, Fe2+, Co2+, Ni2+ and Al3+), serves as a carrier and crosslinker for loading MXene hydrogel induced by the absorbed cations on the skeleton surface and the pores of MS, resulting in the high loading mass MXene aerogels with high mechanical strength. The experimental results show that the Mg-Ti3C2Tx@MS aerogel exhibits the maximum area capacitance of 702.22 mF cm-2 at 3 mA cm-2, and the area capacitance is still 603.12 mF cm-2 even at 100 mA cm-2, indicating the high rate capability with a capacitance retention of 85.89 %. It is worth noting that the constructed asymmetric supercapacitor with activated carbon achieves high energy densities of 104.53 µWh cm-2 and 93.87 µWh cm-2 at 800 µW cm-2 and 7999 µW cm-2, respectively. Furthermore, the asymmetric supercapacitor shows the high cycling stability with 90.2 % capacity retention after 10,000 cycles. This work provides a feasible strategy to prepare Ti3C2Tx MXene aerogels with large layer spacing and high strength for high-performance supercapacitors.

Risk assessment of airborne agricultural pesticide exposure in humans in rural China.

Continuous exposure to airborne pesticides causes their gradual accumulation in the human body, eventually posing a threat to human health. To the best of our knowledge, risk assessment study of pesticide non-occupational exposure to residents in agricultural areas has not been conducted in China. In this study, air samples (gas and dust) were collected from inside and outside residences of seven households and an area near the field in a grain-growing area (wheat and maize rotation) for eight months, and the pesticides present were examined both qualitatively and quantitatively. Using a 95% confidence interval, 9 out of 16 pesticides were detected, namely acetamiprid, acetochlor, atrazine, flucarbazone-sodium, imidacloprid, methyldisulfuron-methyl, nicosulfuron-methyl, pendimethalin, and beta-cyhalothrin, and their safety was subsequently evaluated. The results showed that the inhalation exposure of households to beta-cyhalothrin exceeded the acceptable range in the first residential, and the excess lifetime cancer risk of acetochlor inhalation exposure in six households and area around the field exceeds 1E-6, which highlights the need to strengthen preventive screening for cancer risk.

Changes in Flavor-Related Biomarkers in Pacific Oysters (Crassostrea gigas) Following Microplastic Exposure.

Microplastics have been an emerging threat to filtering species and the ingestion and impacts of microplastics on oysters are a cause for concern. However, much remains unknown about the effects of microplastics on flavor-related biomarkers in oysters. Herein, a laboratory microplastic exposure with concentrations of 1, 10, and 100 mg/L for 15 days was performed to investigate the impacts of microplastics on the flavor parameters of oysters. Exposure to microplastics changed the odor characteristics of oysters. Microplastic exposure had minor effects on the fatty acid composition; however, significant alterations in free amino acids and nucleotides were observed under the 1 and 10 mg/L exposure groups, respectively. The overall results indicated 10 mg/L of microplastic exposure significantly increased the equivalent umami value of oysters. These findings stressed the effects of microplastics on oysters and would be an important reference for the assessment of the potential risks associated with microplastics in marine edible species.

Experimental study of laser spot tracking for underwater optical wireless communication.

In this paper, a novel laser spot tracking algorithm that incorporates the Kalman filter with the continuously adaptive Meanshift algorithm (Cam-Kalm) is proposed and employed in an underwater optical wireless communication (UOWC) system. Since the Kalman filter has the advantage of predicting the state information of the target spot based on its spatial motion features, the proposed algorithm can improve the accuracy and stability of the moving laser spot tracking. A 2 m optical wireless communication experimental system with auto-tracking based on a green laser diode (LD) is built to evaluate the tracking performance of different algorithms. Experimental results verify that the proposed algorithm outperforms conventional tracking algorithms in aspects of tracking accuracy, interference resistance, and response time. With the proposed Cam-Kalm algorithm, the experimental system can establish an effective communication link, while the maximum tracking speed is 20 mm/s given the forward-error-correction (FEC) threshold.

Dual-Frequency Impedance Matching Network Design Using Genetic Algorithm for Power Ultrasound Transducer.

Dual-frequency ultrasounds have demonstrated significant potential in augmenting thermal ablation efficiency for tumor treatment. Ensuring proper impedance matching between the dual-frequency transducer and the power amplifier system is imperative for equipment safety. This paper introduces a novel dual-frequency impedance matching network utilizing L-shaped topology and employing a genetic algorithm to compute component values. Implementation involved an adjustable capacitor and inductor network to achieve dual-frequency matching. Subsequently, the acoustic parameters of the dual-frequency HIFU transducer were evaluated before and after matching, and the effects of ultrasound thermal ablation with and without matching were compared. The proposed dual-frequency impedance matching system effectively reduced the standing wave ratio at the two resonance points while enhancing transmission efficiency. Thermal ablation experiments with matching circuits showed improved temperature rise efficiencies at both frequencies, resulting in an expanded ablation zone. The dual-frequency impedance matching method significantly enhances the transmission efficiency of the dual-frequency ultrasound system at two operational frequencies, thereby ensuring equipment safety. It holds promising prospects for application in dual-frequency ultrasound treatment.

Impact of the extent and location of liver split on future liver remnant hypertrophy after portal vein ligation in a rat model.

BACKGROUND: To investigate the role and mechanism of liver parenchyma transection in accelerating the regeneration of future liver remnants in rats with portal vein ligation (PVL). METHODS: Rats were randomly divided into the PVL group (90% PVL at the caudate lobe, right lobe , left lateral lobe and left median lobe), associating liver partition and portal vein ligation for staged hepatectomy (portal vein ligation with complete liver parenchyma transection [ALPPS]) group (90% PVL with 80 to 90% liver parenchyma transection), PVL + partial liver partition (PLP) group (90% PVL with 30 to 50% liver parenchyma transection), PVL + partition in the ligated lobe (PLL) group (90% PVL with 40 to 60% liver parenchyma transection in the portal vein ligated lobe), PVL + partition in the remnant lobe (PRL) group (90% PVL with 40 to 60% liver parenchyma transection in the remnant lobe), PVL + radiofrequency ablation (RFA) group (90% PVL with splenic ablation) and sham operation (sham) group. The animals were killed at 4 time points of postoperative days 1, 3, 5, and 7. Six rats were killed at each time point, with 24 rats in each group. The weights of the future liver remnant and whole liver were measured. Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were analyzed by using an automatic biochemical analyzer. Serum tumor necrosis factor-α, interleukin-6, and hepatocyte growth factor were measured by enzyme-linked immunosorbent assay. The expression of cell proliferating nuclear antigen (Ki67) and phosphorylated histone H3 was detected by immunohistochemistry, and the positive rate was calculated. RESULTS: The ALPPS group displayed the highest FLR weight to body weight ratio compared with that of the other groups (P < .05), and the partial liver split (PVL + PLP) group also displayed higher remnant weight to body weight ratio than the ectopic liver split (PVL + PLL and PVL + PRL) groups (P < .05). During the first 7 days after surgery the cytokine levels of the ALPPS, PVL + PLP, PVL + PLL and PVL + PRL groups were comparable (P > .05). The PVL + PLP, PVL + PLL, PVL + PRL and PVL + RFA groups showed similar necrotic areas in the portal vein ligated lobe (P > .05). A hemodynamic study revealed that a liver split along the demarcation line could further increase the portal pressure of the FLR and both the split site and completeness were associated with portal hemodynamic alternations and liver hypertrophy. Extrahepatic organ injury (eg, spleen ablation) also has a significant impact on portal hemodynamics and liver regeneration. CONCLUSION: Complete liver splitting along the demarcation line induced higher portal vein pressure and more rapid FLR hypertrophy than partial or ectopic liver splitting after PVL. The portal hemodynamic alterations after liver split rather than inflammatory cytokine release may be the major cause of ALPPS-induced rapid liver hypertrophy.

Hyaluronic acid-decorated curcumin-based coordination nanomedicine for enhancing the infected diabetic wound healing.

Persistent over-oxidation, inflammation and bacterial infection are the primary reasons for impaired wound repairing in diabetic patients. Therefore, crucial strategies to promote diabetic wound repairing involve suppressing the inflammatory response, inhibiting bacterial growth and decreasing reactive oxygen species (ROS) within the wound. In this work, we develop a multifunctional nanomedicine (HA@Cur/Cu) designed to facilitate the repairing process of diabetic wound. The findings demonstrated that the synthesized infinite coordination polymers (ICPs) was effective in enhancing the bioavailability of curcumin and improving the controlled drug release at the site of inflammation. Furthermore, in vitro and in vivo evaluation validate the capacity of HA@Cur/Cu to inhibit bacterial growth and remove excess ROS and inflammatory mediators, thereby significantly promoting the healing of diabetic wound in mice. These compelling findings strongly demonstrate the enormous promise of this multifunctional nanomedicine for the treatment of diabetic wound.

Current-Controlled Electrochemical Approach Toward Mono- and Trifluorinated Isoindolin-1-one Derivatives.

An electrochemical intramolecular 5-exo-dig aza-cyclization of 2-alkynylbenzamides and subsequent nucleophilic fluorination have been developed to afford the highly selective synthesis of mono- and trifluorinated isoindolin-1-one derivatives. This work demonstrates the unique capability of synthetic electrochemistry in controlling reaction selectivity through the applied electrolytic parameters. In addition, the obtained monofluorinated 3-methyleneisoindolin-1-one (19) displays interesting photophysical properties that are not observed in its nonfluorinated analog.

pH/chitinase dual stimuli-responsive essential oil-delivery system based on mesoporous silica nanoparticles for control of rice blast.

BACKGROUND: Owing to their surface modifiability, smart mesoporous silica nanoparticles (MSNs) can be designed to respond to plant disease-microenvironmental stimuli, thereby achieving on-demand release of active ingredients to control disease by effectively improving citral (CT) stability. RESULTS: A pH/chitinase dual stimuli-responsive essential oil-delivery system (CT@HMS@CH/TA) was successfully fabricated by encapsulating CT in hollow mesoporous silica (HMS), and coating with tannic acid (TA) and chitosan (CH) within HMS by using the layer-by-layer assembly technique (LbL). CT@HMS@CH/TA with an average particle size of 125.12 ± 0.12 nm and a hollow mesoporous nanostructure showed high CT-loading efficiency (16.58% ± 0.17%). The photodegradation rate of CT@HMS@CH/TA under UV irradiation (48 h) was only 15.31%, indicating a 3.34-fold UV stability improvement. CT@HMS@CH/TA exhibited a higher CT release rate in response to acidic pH and the presence of chitinase, simulating the prevailing conditions as Magnaporthe oryzae infection. Furthermore, CT@HMS@CH/TA exhibited better adhesion without affecting normal rice growth, significantly upregulating chitinase gene expression and enhancing chitinase activity on M. oryzae, thus enhancing CT antifungal activity. CONCLUSION: CT@HMS@CH/TA improved CT stability and showed intelligent, controlled release-performance and higher antifungal efficacy, thus providing a new strategy for efficient application of essential oils for green control of rice blast disease. © 2024 Society of Chemical Industry.

Multiplex Assay of Cytokines with Tunable Detection Ranges for the Precise Diagnosis of Breast Cancer.

Precise profiling of the cytokine panel consisting of different levels of cytokines can provide personalized information about several diseases at certain stages. In this study, we have designed and fabricated an "all-in-one" diagnostic tool kit to bioassay multiple inflammatory cytokines ranging from picograms per milliliter to µg/mL in a small cytokine panel. Taking advantage of the kit fabricated by the DNA-encoded assembly of nanocatalysts in dynamic regulation and signal amplification, we have demonstrated the multiplex, visual, and quantitative detection of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) with limits of detection of 1.6 ng/mL (61.54 pM), 20 pg/mL (1.57 pM), and 4 pg/mL (0.19 pM), respectively. This diagnostic tool kit can work well with commercial kits for detecting serum cytokines from breast cancer patients treated with immunotherapies. Furthermore, a small cytokine panel composed of CRP, PCT, and IL-6 is revealed to be significantly heterogeneous in each patient and highly dynamic for different treatment courses, showing promise as a panel of quantitative biomarker candidates for individual treatments. So, our work may provide a versatile diagnostic tool kit for the visual detection of clinical biomarkers with an adjustable broad detection range.

Design principles for inflammasome inhibition by pyrin-only-proteins.

Inflammasomes are filamentous signaling platforms essential for host defense against various intracellular calamities such as pathogen invasion and genotoxic stresses. However, dysregulated inflammasomes cause an array of human diseases including autoinflammatory disorders and cancer. It was recently identified that endogenous pyrin-only-proteins (POPs) regulate inflammasomes by directly inhibiting their filament assembly. Here, by combining Rosetta in silico, in vitro, and in cellulo methods, we investigate the target specificity and inhibition mechanisms of POPs. We find here that POP1 is ineffective in directly inhibiting the central inflammasome adaptor ASC. Instead, POP1 acts as a decoy and targets the assembly of upstream receptor pyrin-domain (PYD) filaments such as those of AIM2, IFI16, NLRP3, and NLRP6. Moreover, not only does POP2 directly suppress the nucleation of ASC, but it can also inhibit the elongation of receptor filaments. In addition to inhibiting the elongation of AIM2 and NLRP6 filaments, POP3 potently suppresses the nucleation of ASC. Our Rosetta analyses and biochemical experiments consistently suggest that a combination of favorable and unfavorable interactions between POPs and PYDs is necessary for effective recognition and inhibition. Together, we reveal the intrinsic target redundancy of POPs and their inhibitory mechanisms.

Synthesis, Characterization, and Properties of Sila-Annulated Phenanthrene Imides.

A series of sila-annulated phenanthrene imides were synthesized through a three-step synthetic route, which represent a hybrid class of biphenyl-based π-conjugated molecules incorporating an imide unit and silole. A comprehensive investigation of their structural, photophysical, and electronic properties was studied by experiment and theoretical calculations. Notably, sila-annulated phenanthrene imides with significant aggregation-induced emission (AIE) properties were observed.

Effect of high-field iMRI guided resection in cerebral glioma surgery: A randomized clinical trial.

BACKGROUND: Extent of resection (EOR) in glioma contributes to longer survival. The purpose of NCT01479686 was to prove whether intraoperative magnetic resonance imaging (iMRI) increases EOR in glioma surgery and benefit survival. METHODS: Patients were randomized (1:1) to receive the iMRI (n = 161) or the conventional neuronavigation (n = 160). The primary endpoint was gross total resection (GTR); secondary outcomes reported were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 188 high-grade gliomas (HGGs) and 133 low-grade gliomas (LGGs) were enrolled. GTR was 83.85% in the iMRI group vs. 50.00% in the control group (P < 0.0001). In 321 patients, the median PFS (mPFS) was 65.12 months in the iMRI group and 61.01 months in the control group (P = 0.0202). For HGGs, mPFS was improved in the iMRI group (19.32 vs. 13.34 months, P = 0.0015), and a trend of superior OS compared with control was observed (29.73 vs. 25.33 months, P = 0.1233). In the predefined eloquent area HGG subgroup, mPFS, and mOS were 20.47 months and 33.58 months in the iMRI vs. 12.21 months and 21.16 months in the control group (P = 0.0098; P = 0.0375, respectively). From the exploratory analyses of HGGs, residual tumor volume (TV) < 1.0 cm3 decreased the risk of survival (mPFS: 18.99 vs. 9.43 months, P = 0.0055; mOS: 29.77 vs. 18.10 months, P = 0.0042). LGGs with preoperative (pre-OP) TV > 43.1 cm3 and postoperative (post-OP) TV > 4.6 cm3 showed worse OS (P= 0.0117) CONCLUSIONS: It showed that iMRI significantly increased EOR and indicated survival benefits for HGGs, particularly eloquent HGGs. Residual TV in either HGGs or LGGs is a prognostic factor for survival.

Adverse Impact of Sodium Bicarbonate Administration on Multiple Outcomes in Acute Pancreatitis Patients With Hyperlactatemia.

OBJECTIVE: Hyperlactatemia is likely to occur among patients with acute pancreatitis (AP). Sodium bicarbonate (SB) therapy could be applied to correct potential detrimental acidic disturbances, but the exact impact of SB treatment is unknown. This study aims to investigate the impact of SB on AP patients complicated with hyperlactatemia. METHODS: The study was conducted based on the database named Medical Information Mart for Intensive Care-IV (MIMIC-IV). Propensity matching (PSM) and inverse probability weighting (IPTW) were used to balance the baseline differences. Multivariate regression and marginal structural Cox models were performed to investigate the association between SB and multiple outcomes. RESULTS: Three hundred fifty-three AP patients with hyperlactatemia (initial serum lactate, >2.0 mmol/L) were extracted from the MIMIC-IV database. We found that SB treatment was significantly associated with worse multi-outcomes of AP patients with hyperlactatemia (in-hospital mortality: hazard ratio, 2.46; 95% confidence interval, 1.38-4.39; P < 0.01). Further analysis through marginal structural Cox models showed that SB had adverse impact on in-hospital prognosis of patients with severe lactic acidosis (pH < 7.15,lactate > 2.0 mmol/L). CONCLUSION: Sodium bicarbonate might not be an appropriate treatment for AP patients with hyperlactatemia (lactate > 2.0 mmol/L) or with severe lactic acidosis (pH < 7.15, lactate > 2.0 mmol/L).

[Analysis on Driving Factors, Reduction Potential, and Environmental Effect of Inorganic Fertilizer Input in Chongqing].

In this study, we sought to quantify the effect of planting structure change on fertilizer input and environmental cost in Chongqing and develop scientific and rational strategies for chemical fertilizer reduction. Based on the crop fertilizer quota standard and large sample farmer survey data under the medium productivity level in Chongqing, we evaluated and analyzed the application reduction potential and environmental benefits of fertilizer with the difference method and life cycle assessment. The results showed that:① since Chongqing became a municipality directly under the central government (1997), Chongqing crop planting structure had greatly changed, and the proportion of food crop (rice, corn, wheat, bean, and potato) decreased by 21%. The area of fruits and vegetables increased from 3.36×105 hm2 to 1.05×106 hm2, and their proportion increased by 20%. ② Nearly 55% of fertilizers had been consumed by vegetable (37%) and citrus production systems, and 11%, 12%, and 12% of fertilizers were consumed by rice, corn, and potato, respectively. ③ The total fertilizer reduction of the Chongqing planting industry could reach up to 1.69×105 tons during the period of "the 14th Five-Year Plan," with a fertilizer reduction potential of 18.6%. The fertilizer reduction potential (reduction amount) of rice, corn, citrus, and vegetables would reach 0.3% (2.9×102 tons), 12% (1.45×104 tons), 21% (3.65×104 tons), and 30% (1.18×105 tons), respectively. On the other hand, the rape system was insufficient in phosphorus potassium fertilizers, and the corn tended to be insufficient in potash fertilizer. ④ The current production level was low, and the nitrogen loss, greenhouse gas emissions, and eutrophication potential in the planting industry of Chongqing reached 1.81×105 tons (N), 1.43×107 tons (CO2-eq), and 1.74×105 tons (PO4-eq). With the increase in the realization degree of the crop quota standard (60%-100%), the reactive nitrogen loss, greenhouse gas emissions, and eutrophication potential decreased by 14.9%-24.9%, 10.1%-16.7%, and 13.8%-23%, respectively. The structure of the planting industry in Chongqing significantly changed, the total fertilizer consumption in Chongqing tended to decline gradually, and the fertilization intensity of commercial crops stayed at a high level. The agricultural fertilizer reduction potential and the reactive nitrogen and greenhouse gas emission reduction potential were large, especially for citrus and vegetable production systems. However, it is also necessary to pay attention to insufficient corn potash fertilizer and rape phosphorus potassium fertilizer investment and carry out collaborative promotion of fertilizer reduction.

Active Materials for Functional Origami.

In recent decades, origami has been explored to aid in the design of engineering structures. These structures span multiple scales and have been demonstrated to be used toward various areas such as aerospace, metamaterial, biomedical, robotics, and architectural applications. Conventionally, origami or deployable structures have been actuated by hands, motors, or pneumatic actuators, which can result in heavy or bulky structures. On the other hand, active materials, which reconfigure in response to external stimulus, eliminate the need for external mechanical loads and bulky actuation systems. Thus, in recent years, active materials incorporated with deployable structures have shown promise for remote actuation of light weight, programmable origami. In this review, active materials such as shape memory polymers (SMPs) and alloys (SMAs), hydrogels, liquid crystal elastomers (LCEs), magnetic soft materials (MSMs), and covalent adaptable network (CAN) polymers, their actuation mechanisms, as well as how they have been utilized for active origami and where these structures are applicable is discussed. Additionally, the state-of-the-art fabrication methods to construct active origami are highlighted. The existing structural modeling strategies for origami, the constitutive models used to describe active materials, and the largest challenges and future directions for active origami research are summarized.

Di-aldehyde tunicate cellulose nanocrystal (D-tCNC) aerogels for drug delivery: Effect of D-tCNC composition on aerogel structure and release properties.

Aerogels as drug carriers have the characteristics of a large specific surface area, high porosity and an elastic skeleton structure. Compared with traditional drug carriers, the use of aerogels as drug carriers can avoid the complexity of drug delivery and improve the efficiency of drug loading. In this work, the oxidation of tunicate cellulose nanocrystals (tCNCs) with NaIO4 was used to prepare di-aldehyde tunicate cellulose nanocrystals (D-tCNCs). Tetracycline (TC) was used as a drug model and pH-responsive drug-loaded aerogels were prepared by the Schiff base reaction between TC and the aldehyde group on D-tCNCs. The chemical structure, crystallinity, morphology, compression properties, porosity, swelling rate and drug loading properties were investigated by FT-IR, XRD, SEM and universal testing machines. The results showed that the porosity and equilibrium swelling ratio of the D-tCNC-TC aerogels were 95.87 % and 17.52 g/g, respectively. The stress of the D-tCNC-TC aerogel at 15 % compression was 0.07 MPa. Moreover, the analysis of drug-loaded aerogels indicated that the drug loading and encapsulation rates of D-tCNC-TC aerogels were 16.86 % and 78.75 %, respectively. In in vitro release experiments, the cumulative release rate of drug-loaded aerogel at pH = 1.2 and pH = 7.4 was 87.5 % and 79.3 %, respectively. These results indicated that D-tCNC-TC aerogels have good drug loading capacity and are pH-responsive in the pH range of 1.2 to 7.4. The prepared D-tCNC-TC aerogels are expected to be applied in drug delivery systems.

Fully Active Delivery of Nanodrugs In Vivo via Remote Optical Manipulation.

The active delivery of nanodrugs has been a bottleneck problem in nanomedicine. While modification of nanodrugs with targeting agents can enhance their retention at the lesion location, the transportation of nanodrugs in the circulation system is still a passive process. The navigation of nanodrugs with external forces such as magnetic field has been shown to be effective for active delivery, but the existing techniques are limited to specific materials like magnetic nanoparticles. In this study, an alternative actuation method is proposed based on optical manipulation for remote navigation of nanodrugs in vivo, which is compatible with most of the common drug carriers and exhibits significantly higher manipulation precision. By the programmable scanning of the laser beam, the motion trajectory and velocity of the nanodrugs can be precisely controlled in real time, making it possible for intelligent drug delivery, such as inverse-flow transportation, selective entry into specific vascular branch, and dynamic circumvention across obstacles. In addition, the controlled mass delivery of nanodrugs can be realized through indirect actuation by the microflow field. The developed optical manipulation method provides a new solution for the active delivery of nanodrugs, with promising potential for the treatment of blood diseases such as leukemia and thrombosis.

Enhanced performance of enzymes confined in biocatalytic hydrogen-bonded organic frameworks for sensing of glutamate in the central nervous system.

Glutamate (Glu) is a key excitatory neurotransmitter associated with various neurological disorders in the central nervous system, so its measurement is vital to both basic research and biomedical application. In this work, we propose the first example of using biocatalytic hydrogen-bonded organic frameworks (HOFs) as the hosting matrix to encapsulate glutamate oxidase (GLOD) via a de novo approach, fabricating a cascaded-enzyme nanoreactor for Glu biosensing. In this design, the ferriporphyrin ligands can assemble to form Fe-HOFs with high catalase-like activity, while offering a scaffold for the in-situ immobilization of GLOD. Moreover, the formed GLOD@Fe-HOFs are favorable for the efficient diffusion of Glu into the active sites of GLOD via the porous channels, accelerating the cascade reaction with neighboring Fe-HOFs. Consequently, the constructed nanoreactor can offer superior activity and operational stability in the catalytic cascade for Glu biosensing. More importantly, rapid and selective detection can be achieved in the cerebrospinal fluid (CSF) collected from mice in a low sample consumption. Therefore, the successful fabrication of enzyme@HOFs may offer promise to develop high-performance biosensor for further biomedical applications.