Ability of dynamic gadoxetic acid-enhanced magnetic resonance imaging combined with water-specific T1 mapping to reflect inflammation in a rat model of early-stage nonalcoholic steatohepatitis.

Background: Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) has shown potential in reflecting the hepatic function alterations in nonalcoholic steatohepatitis (NASH). The purpose of this study was to evaluate whether Gd-EOB-DTPA combined with water-specific T1 (wT1) mapping can be used to detect liver inflammation in the early-stage of NASH in rats. Methods: In this study, 54 rats with methionine- and choline-deficient (MCD) diet-induced NASH and 10 normal control rats were examined. A multiecho variable flip angle gradient echo (VFA-GRE) sequence was performed and repeated 40 times after the injection of Gd-EOB-DTPA. The wT1 of the liver and the reduction rate of wT1 (rrT1) were calculated. All rats were histologically evaluated and grouped according to the NASH Clinical Research Network scoring system. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of Gd-EOB-DTPA transport genes. Analysis of variance and least significant difference tests were used for multiple comparisons of quantitative results between all groups. Multiple regression analysis was applied to identify variables associated with precontrast wT1 (wT1pre), and receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance. Results: The rats were grouped according to inflammatory stage (G0 =4, G1 =15, G2 =12, G3 =23) and fibrosis stage (F0 =26, F1 =19, F2 =9). After the infusion of Gd-EOB-DTPA, the rrT1 showed significant differences between the control and NASH groups (P<0.05) but no difference between the different inflammation and fibrosis groups at any time points. The areas under curve (AUCs) of rrT1 at 10, 20, and 30 minutes were only 0.53, 0.58, and 0.61, respectively, for differentiating between low inflammation grade (G0 + G1) and high inflammation grade (G2 + G3). The MRI findings were verified by qRT-PCR examination, in which the Gd-EOB-DTPA transporter expressions showed no significant differences between any inflammation groups. Conclusions: The wT1 mapping quantitative method combined with Gd-EOB-DTPA was not capable of discerning the inflammation grade in a rat model of early-stage NASH.

Biological characteristics of mechanosensitive channels MscS and MscL in Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is an important respiratory pathogen that can cause porcine contagious pleuropneumonia (PCP), resulting in significant economic losses in swine industry. Microorganisms are subjected to drastic changes in environmental osmolarity. In order to alleviate the drastic rise or fall of osmolarity, cells activate mechanosensitive channels MscL and MscS through tension changes. MscL not only regulates osmotic pressure but also has been reported to secrete protein and uptake aminoglycoside antibiotic. However, MscL and MscS, as the most common mechanosensitive channels, have not been characterized in A. pleuropneumoniae. In this study, the osmotic shock assay showed that MscL increased sodium adaptation by regulating cell length. The results of MIC showed that deletion of mscL decreased the sensitivity of A. pleuropneumoniae to multiple antibiotics, while deletion of mscS rendered A. pleuropneumoniae hypersensitive to penicillin. Biofilm assay demonstrated that MscL contributed the biofilm formation but MscS did not. The results of animal assay showed that MscL and MscS did not affect virulence in vivo. In conclusion, MscL is essential for sodium hyperosmotic tolerance, biofilm formation, and resistance to chloramphenicol, erythromycin, penicillin, and oxacillin. On the other hand, MscS is only involved in oxacillin resistance.IMPORTANCEBacterial resistance to the external environment is a critical function that ensures the normal growth of bacteria. MscL and MscS play crucial roles in responding to changes in both external and internal environments. However, the function of MscL and MscS in Actinobacillus pleuropneumoniae has not yet been reported. Our study shows that MscL plays a significant role in osmotic adaptation, antibiotic resistance, and biofilm formation of A. pleuropneumoniae, while MscS only plays a role in antibiotic resistance. Our findings provide new insights into the functional characteristics of MscL and MscS in A. pleuropneumoniae. MscL and MscS play a role in antibiotic resistance and contribute to the development of antibiotics for A. pleuropneumoniae.

Recent progress in biosensor regeneration techniques.

Biosensors are widely used in various applications, from medical diagnostics to environmental monitoring. Their widespread and continuous use necessitates regeneration methods to ensure cost-effectiveness and sustainability. In the realm of advancing human-centric bioelectronics for continuous monitoring, employing these sensors for real-time, in situ detection of biomarkers presents a considerable challenge. This mini-review examines diverse strategies utilized for the regeneration of biosensors, categorizing them based on their underlying mechanisms and discussing representative works. We explore methods ranging from surface engineering/re-functionalization, chemical treatments, allosteric regulation of bioreceptors, to manipulations of electric/magnetic fields, highlighting their working principles and exemplary studies. The advantages of each method, such as simplicity, high regeneration efficiency, and versatility, are discussed alongside their challenges, including degradation over cycles, limited applicability, and potential damage to sensors. As the demand for continuous and real-time biosensing escalates, the development of efficient and reliable regeneration strategies becomes essential. This mini-review offers an overview of the current landscape of biosensor regeneration, aiming to guide future research and innovations in this area.

The change of healthcare service in Chinese patients with inflammatory bowel disease during the pandemic: a national multicenter cross-sectional study.

The pandemic of COVID-19 was a major public health events and had a deeply impact on the healthcare acquired by patients with inflammatory bowel disease (IBD). The purpose of this study was to evaluate the long-term impacts on healthcare service in Chinese IBD patients under the dynamic zero-COVID strategy. The study was performed in the Inflammatory Bowel Disease Quality of Care Centers in mainland China in 2021. The data about the healthcare was collected by a 44-item questionnaire. Totally 463 were from ulcerative colitis (UC) patients and 538 from Crohn's disease (CD) patients were included in the study. The pandemic impacted 37.5% patients on their treatment, and the biggest problem was unable to follow up timely (77.9%). There was a significant increase in healthcare costs in CD (P < 0.001) and no significant change in UC (P = 0.14) after the outbreak. Both UC and CD had an increase in the frequency of outpatient visits (UC 5.07 vs. 4.54, P = 0.001; CD 6.30 vs. 5.76, P = 0.002), and hospitalizations (UC 1.30 vs. 1.02, P < 0.001; CD 3.55 vs. 2.78, P < 0.001). The hospitalization rate in UC reduced slightly (40.2% vs. 42.8%, P = 0.423) after the outbreak, but it significantly increased in CD (75.8% vs. 67.8%, P = 0.004). The rate of biologics had significant increased (UC 11.2% vs. 17.7%, P = 0.005; CD 53.2% vs. 71.0%, P < 0.001). Besides, the proportion of people using telemedicine also increased from 41.6% to 55.1% (P < 0.001). However, 82.8% patients still preferred face-to-face visits. Recurrent outbreaks and the regular pandemic prevention and control policy had a long-term impact on medical care service for IBD patients. The preferred mode of healthcare was still face-to-face visit. It will be a long way to go in the construction of telemedicine in China.

The two-component system CpxAR is required for the high potassium stress survival of Actinobacillus pleuropneumoniae.

Introduction: Actinobacillus pleuropneumoniae is an important respiratory pathogen, which can cause porcine contagious pleuropneumonia and lead to great economic losses to worldwide swine industry. High potassium is an adverse environment for bacteria, which is not conducive to providing turgor pressure for cell growth and division. Two-component system CpxAR is an important regulatory system of bacteria in response to environmental changes, which is involved in a variety of biological activities, such as antibiotic resistance, periplasmic protein folding, peptidoglycan metabolism and so on. Methods: However, little is known about the role of CpxAR in high potassium stress in A. pleuropneumoniae. Here, we showed that CpxAR is critical for cell division of A. pleuropneumoniae under high potassium (K+) stress. Results: qRT-PCR analysis found that CpxAR positively regulated the cell division genes ftsEX. In addition, we also demonstrated that CpxR-P could directly bind the promoter region of the cell division gene ftsE by EMSA. Discussion: In conclusion, our results described a mechanism where CpxAR adjusts A. pleuropneumoniae survival under high-K+ stress by upregulating the expression of the cell division proteins FtsE and FtsX. These findings are the first to directly demonstrate CpxAR-mediated high-K+ tolerance, and to investigate the detailed molecular mechanism.

Flexible, Miniaturized Sensing Probes Inspired by Biofuel Cells for Monitoring Synaptically Released Glutamate in the Mouse Brain.

Chemical biomarkers in the central nervous system can provide valuable quantitative measures to gain insight into the etiology and pathogenesis of neurological diseases. Glutamate, one of the most important excitatory neurotransmitters in the brain, has been found to be upregulated in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, stroke, epilepsy, chronic pain, and migraines. However, quantitatively monitoring glutamate release in situ has been challenging. This work presents a novel class of flexible, miniaturized probes inspired by biofuel cells for monitoring synaptically released glutamate in the nervous system. The resulting sensors, with dimensions as low as 50 by 50 µm, can detect real-time changes in glutamate within the biologically relevant concentration range. Experiments exploiting the hippocampal circuit in mice models demonstrate the capability of the sensors in monitoring glutamate release via electrical stimulation using acute brain slices. These advances could aid in basic neuroscience studies and translational engineering, as the sensors provide a diagnostic tool for neurological disorders. Additionally, adapting the biofuel cell design to other neurotransmitters can potentially enable the detailed study of the effect of neurotransmitter dysregulation on neuronal cell signaling pathways and revolutionize neuroscience.

Hypoxia induces the production of epithelial-derived cytokines in eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Hypoxia plays a significant role in the pathogenesis of chronic rhinosinusitis (CRS). However, the role and mechanism of hypoxia in the type 2 immune response in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remain unclear. METHODS: The expression of hypoxia-inducible factor-1α (HIF-1α) and epithelial-derived cytokines (EDCs), including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), was detected in nasal polyps via immunohistochemical analysis. The relationship between HIF-1α and EDCs was also elucidated using Pearson's correlation. Moreover, primary human nasal epithelial cells (HNECs) and a mouse model of ECRSwNP were employed to elucidate the role and mechanism of hypoxia in type 2 immune responses. RESULTS: HIF-1α, IL-25, IL-33, and TSLP expression levels were upregulated in the non-ECRSwNP and ECRSwNP groups compared with the control group, with the ECRSwNP group having the highest HIF-1α and EDC expression levels. Additionally, HIF-1α was positively correlated with IL-25 and IL-33 in the ECRSwNP group. Meanwhile, treatment with a HIF-1α inhibitor, PX-478, inhibited the hypoxia-induced increase in the mRNA and protein expression of EDCs and type 2 cytokines in HNECs. Similarly, in vivo, PX-478 inhibited EDC expression in the sinonasal mucosa of mice with ECRSwNP. CONCLUSIONS: Hypoxia induces EDC expression by upregulating HIF-1α levels, thereby promoting type 2 immune responses and the development of ECRSwNP. Hence, targeting HIF-1α may represent an effective therapeutic strategy for ECRSwNP.

Effective Treatment of Haemophilus influenzae-Induced Bacterial Conjunctivitis by a Bioadhesive Nanoparticle Reticulate Structure.

Ocular formulations should provide an effective antibiotic concentration at the site of infection to treat bacterial eye infections. However, tears and frequent blinking accelerate the drug clearance rate and limit drug residence time on the ocular surface. This study describes a biological adhesion reticulate structure (BNP/CA-PEG) consisting of antibiotic-loaded bioadhesion nanoparticles (BNP/CA), with an average 500-600 nm diameter, and eight-arm NH2-PEG-NH2 for local and extended ocular drug delivery. This retention-prolonging effect is a function of the Schiff base reaction between groups on the surface of BNP and amidogen on PEG. BNP/CA-PEG showed significantly higher adhesion properties and better treatment efficacy in an ocular rat model with conjunctivitis in comparison to non-adhesive nanoparticles, BNP, or free antibiotics. Both in vivo safety experiment and in vitro cytotoxicity test verified the biocompatibility and biosafety of the biological adhesion reticulate structure, indicating a promising translational prospect for further clinical use.

Visualization of porosity and pore size gradients in electrospun scaffolds using laser metrology.

We applied a recently developed method, laser metrology, to characterize the influence of collector rotation on porosity gradients of electrospun polycaprolactone (PCL) widely investigated for use in tissue engineering. The prior- and post-sintering dimensions of PCL scaffolds were compared to derive quantitative, spatially-resolved porosity 'maps' from net shrinkage. Deposited on a rotating mandrel (200 RPM), the central region of deposition reaches the highest porosity, ~92%, surrounded by approximately symmetrical decreases to ~89% at the edges. At 1100 RPM, a uniform porosity of ~88-89% is observed. At 2000 RPM, the lowest porosity, ~87%, is found in the middle of the deposition, rebounding to ~89% at the edges. Using a statistical model of random fiber network, we demonstrated that these relatively small changes in porosity values produce disproportionately large variations in pore size. The model predicts an exponential dependence of pore size on porosity when the scaffold is highly porous (e.g., >80%) and, accordingly, the observed porosity variation is associated with dramatic changes in pore size and ability to accommodate cell infiltration. Within the thickest regions most likely to 'bottleneck' cell infiltration, pore size decreases from ~37 to 23 µm (38%) when rotational speeds increased from 200 to 2000 RPM. This trend is corroborated by electron microscopy. While faster rotational speeds ultimately overcome axial alignment induced by cylindrical electric fields associated with the collector geometry, it does so at the cost of eliminating larger pores favoring cell infiltration. This puts the bio-mechanical advantages associated with collector rotation-induced alignment at odds with biological goals. A more significant decrease in pore size from ~54 to ~19 µm (65%), well below the minimum associated with cellular infiltration, is observed from enhanced collector biases. Finally, similar predictions show that sacrificial fiber approaches are inefficient in achieving cell-permissive pore sizes.

Study on Water Resource Carrying Capacity of Zhengzhou City Based on DPSIR Model.

Based on the driving force-pressure-state-impact-response (DPSIR) model, a comprehensive evaluation index system is constructed. The index weight is determined by the combination weighting method in combination with the data of 2010-2019. The TOPSIS model is used to comprehensively analyze the water resource carrying capacity of Zhengzhou as the central city in China with a developed economy and relatively short water resources. The study results are as follows. (1) During the sample period, the comprehensive evaluation value of water resources carrying capacity of Zhengzhou increases from 0.4183 in 2010 to 0.5560 in 2019, with an overall fluctuating rise. Simultaneously, the water resource carrying capacity grade improves from Grade III (normal carrying capacity) to Grade II (good carrying capacity). (2) The contribution of each subsystem to the comprehensive evaluation value increases year by year. Among them, S subsystem and I subsystem make the largest contribution to the comprehensive carrying capacity. R subsystem makes a relatively stable contribution to the overall carrying capacity. Affected by GDP growth rate and uneven temporal-spatial distribution of water resources in Zhengzhou, the D subsystem and P subsystem of water resource carrying capacities show the fluctuating change. Finally, based on the above conclusions, this paper puts forward the countermeasures and suggestions to improve the level of water resource carrying capacity of Zhengzhou.

Characterization of glucose metabolism in breast cancer to guide clinical therapy.

Background: Breast cancer (BRCA) ranks as a leading cause of cancer death in women worldwide. Glucose metabolism is a noticeable characteristic of the occurrence of malignant tumors. In this study, we aimed to construct a novel glycometabolism-related gene (GRG) signature to predict overall survival (OS), immune infiltration and therapeutic response in BRCA patients. Materials and methods: The mRNA sequencing and corresponding clinical data of BRCA patients were obtained from public cohorts. Lasso regression was applied to establish a GRG signature. The immune infiltration was evaluated with the ESTIMATE and CIBERSORT algorithms. The drug sensitivity was estimated using the value of IC50, and further forecasted the therapeutic response of each patient. The candidate target was selected in Cytoscape. A nomogram was constructed via the R package of "rms". Results: We constructed a six-GRG signature based on CACNA1H, CHPF, IRS2, NT5E, SDC1 and ATP6AP1, and the high-risk patients were correlated with poorer OS (P = 2.515 × 10-7). M2 macrophage infiltration was considerably superior in high-risk patients, and CD8+ T cell infiltration was significantly higher in low-risk patients. Additionally, the high-risk group was more sensitive to Lapatinib. Fortunately, SDC1 was recognized as candidate target and patients had a better OS in the low-SDC1 group. A nomogram integrating the GRG signature was developed, and calibration curves were consistent between the actual and predicted OS. Conclusions: We identified a novel GRG signature complementing the present understanding of the targeted therapy and immune biomarker in breast cancer. The GRGs may provide fresh insights for individualized management of BRCA patients.

Monosynaptic targets of utricular afferents in the larval zebrafish.

The larval zebrafish acquires a repertoire of vestibular-driven behaviors that aid survival early in development. These behaviors rely mostly on the utricular otolith, which senses inertial (tilt and translational) head movements. We previously characterized the known central brainstem targets of utricular afferents using serial-section electron microscopy of a larval zebrafish brain. Here we describe the rest of the central targets of utricular afferents, focusing on the neurons whose identities are less certain in our dataset. We find that central neurons with commissural projections have a wide range of predicted directional tuning, just as in other vertebrates. In addition, somata of central neurons with inferred responses to contralateral tilt are located more laterally than those with inferred responses to ipsilateral tilt. Many dorsally located central utricular neurons are unipolar, with an ipsilateral dendritic ramification and commissurally projecting axon emerging from a shared process. Ventrally located central utricular neurons tended to receive otolith afferent synaptic input at a shorter distance from the soma than in dorsally located neurons. Finally, we observe an unexpected synaptic target of utricular afferents: afferents from the medial (horizontal) semicircular canal. Collectively, these data provide a better picture of the gravity-sensing circuit. Furthermore, we suggest that vestibular circuits important for survival behaviors develop first, followed by the circuits that refine these behaviors.

Rhythmic auditory stimulation promotes gait recovery in Parkinson's patients: A systematic review and meta-analysis.

Objective: Using rhythmic auditory stimulation (RAS) to improve gait disturbance in Parkinson's disease (PD) is an available treatment option, yet a consensus on its effectiveness remains controversial. We summarized the effects of RAS on gait, functional activity and quality of life in PD patients through a systematic review and meta-analysis. Methods: PubMed, Embase, Web of Science, Medline, and Cochrane Library databases were initially searched to identify relevant literature up to August 2021. Next, the methodological quality of eligible comparative studies was assessed by the Physiotherapy Evidence Database Scale. The treatment effects to clinical outcome in relation to gait, motor activities, and quality of life were analyzed. Results: A total of 18 studies consisted of 774 subjects were included in this meta-analysis. Comparing with the control group, RAS had significantly increased stride length (p < 0.001), accelerated gait speed (p < 0.001), reduced the occurrence of freezing events during walking (P = 0.009), achieved an improvement in Unified Parkinson's Disease Rating Scale (UPDRS) II (P = 0.030), UPDRS-III (P < 0.001) and Parkinson's Disease Quality of Life Questionnaire (PDQL) (p = 0.009) scores over an interval of 1-26 months. Conclusion: In this meta-analysis of 18 randomized controlled trials, we have demonstrated that RAS improves the general motor functions (UPDRS-III), particularly in gait, mobility and quality of life, in patients with Parkinson's disease.

Organization of the gravity-sensing system in zebrafish.

Motor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion is linked to both developmental sequence and neuronal temporal dynamics. Early-born pathways carrying phasic information preferentially excite fast escape circuits, whereas later-born pathways carrying tonic signals excite slower postural and oculomotor circuits. These results demonstrate that vestibular circuits are organized by tuning direction and dynamics, aligning them with downstream motor circuits and behaviors.

Efficacy and safety of tension band wire versus plate for Mayo II olecranon fractures: a systematic review and meta-analysis.

PURPOSE: For olecranon fractures, the choice of tension band wire (TBW) or plate fixation has long been controversial. Therefore, this study aimed to evaluate the efficacy and safety of TBW and plate in the treatment of patients with Mayo II olecranon fractures by Meta-analysis. METHODS: PubMed, Embase, Cochrane, the Web of Science, China National Knowledge Infrastructure, Wanfang, and China Biomedical Database were searched for randomized controlled trials (RCTs) and cohort studies (CSs) where TBW was compared with plate for Mayo II olecranon fractures (OF). Subsequently, the data were extracted by two reviewers independently and were analysed via RevMan5.4.1. Besides, mean difference (MD), risk ratio (RR), and 95% confidence intervals (CIs) were calculated. Furthermore, Cochrane Risk of Bias Tool 2.0 and Newcastle-Ottawa Scale were adopted for assessing the risk of bias. RESULTS: A total of 1RCT and 10 CSs were included, when 449 cases were treated with TBW and 378 with plate. The plate has favourable postoperative long-term (≥ 1 year) functional score in MEPS (MD: - 3.06; 95% CI - 5.50 to 0.62; P = 0.01; I2 = 41%) and Dash score (MD: 2.32; 95% CI 1.91, 2.73; P < 0.00001; I2 = 0%), also carrying fewer complications (RR: 2.13; 95% CI 1.48, 3.08; P < 0.0001; I2 = 58%). Besides, there exists no significant difference in postoperative long-term (≥ 1 year) elbow flexion (MD: - 1.82°; 95% CI - 8.54, 4.90; P = 0.60; I2 = 71%) and extension deficits (MD: 1.52°; 95% CI - 0.38, 3.42; P = 0.12; I2 = 92%). Moreover, TBW is featured with a shorter operation time (MD = - 5.87 min; 95% CI - 7.93, - 3.82; P < 0.00001; I2 = 0) and less intraoperative bleeding (MD: - 5.33 ml; 95% CI - 8.15, - 2.52; P = 0.0002; I2 = 0). In terms of fracture healing time, it is still controversial. Furthermore, the subgroup analysis has revealed that for Mayo IIA OF, the plate has a better outcome in the long-term (≥ 1 year) postoperative MEPS, the Dash score, and the incidence of postoperative complications than TBW, while there is no significant difference in the long-term (≥ 1 year) postoperative elbow motion between two groups. CONCLUSIONS: Plate has better efficacy and safety for Mayo II OF. Considering that few studies are included in the meta-analysis, more high-quality RCTs are still required to confirm these findings. PROSPERO registration number: CRD42022313855.

Topical formulation based on disease-specific nanoparticles for single-dose cure of psoriasis.

First-line treatments for mild to moderate psoriasis are typically topical formulations containing corticosteroids, however, the therapeutic efficacy of these formulations is compromised by limited penetration and skin retention. Even more challenging, off-target corticosteroids are known to adversely affect healthy skin, including induction of epidermal and dermal atrophy. Here, we report a nanoparticle-based topical formulation that cures psoriasis in a single dose, but leaves healthy skin intact. Specifically, we developed tris(hydroxymethyl)aminomethane-modified bioadhesive nanoparticles (Tris-BNPs) that exploit the high permeability characteristic of psoriasis to penetrate only psoriatic skin but not the healthy skin. Furthermore, as Tris-BNPs diffuse and penetrate into the epidermis, the Tris molecules slowly diffuse away, exposing the aldehyde groups of BNPs, which can bind to amine groups present within lesional skin, leading to long local retention of BNPs in lesions of psoriatic skin. The accumulated BNPs within lesions release corticosteroids over a ~ 3 day period to maintain local drug concentration above the therapeutic level. In addition to deeper penetration and longer retention compared with commercial psoriasis treatments, the topical applied Tris-BNPs were not affected by sweating, humidity, or active wiping due to their preferential accumulation between the stratum corneum and the basal cells of the epidermis. Overall, Tris-BNP as a topical formulation hold promise to overcome the limitations of current psoriasis treatment.

Specific Tumor Cell Detection by a Metabolically Targeted Aggregation-Induced Emission-Based Gold Nanoprobe.

Detection of circulating tumor cells (CTCs) could be widely used for early diagnosis and real-time monitoring of tumor progression in liquid biopsy samples. Compared with normal cells, tumor cells exhibit relatively strong negative surface charges due to the high rate of glycolysis. In this study, a cationic fluorescence "turn-on" aggregation-induced emission (AIE) nanoprobe based on gold nanorods (GNRs) was designed and tested to detect tumor cells specifically. In brief, tetraphenylethene (TPE), an AIE dye, was conjugated to the cationic polymer polyethylenimine (PEI) yielding TPEI. TPEI-PEG-SH was obtained by further functionalizing TPEI with a thiol group. TPEI-PEG-SH was grafted to the surface of GNRs, yielding the cationic AIE nanoprobe, named as GNRs-PEG-TPEI. The nanoprobe was characterized to have a uniform particle size of 172 nm, a strong positive surface charge (+54.87 mV), and a surface modification load of ∼40%. The in vitro stability of GNRs-PEG-TPEI was verified. The cellular imaging results demonstrated that the nanoprobe could efficiently recognize several types of tumor cells including MCF-7, HepG2, and Caco-2 while exhibiting specific fluorescence signals only after interacting with tumor cells and minimal background interference. In addition, the study investigated the toxicity of the nanoprobe to the captured cells and proved the safety of the nanoprobe. In conclusion, a specific and efficient nanoprobe was developed for capture and detection of different types of tumor cells based on their unique metabolic characteristics. It holds great promise for achieving early diagnosis and monitoring the tumor progression by detecting the CTCs in clinical liquid biopsy samples.

Poly(lactic acid)-hyperbranched polyglycerol nanoparticles enhance bioadhesive treatment of esophageal disease and reduce systemic drug exposure.

The effective treatment of esophageal disease represents a significant unmet clinical need, as existing treatments often lead to unnecessary systemic drug exposure and suboptimal concentrations at the disease site. Here, surface-modified bioadhesive poly(lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs), with an average 100-200 nm diameter, were developed for local and sustained esophageal drug delivery. BNPs showed significantly higher adhesion and permeation into ex vivo human and rat esophageal tissue than non-adhesive nanoparticles (NNPs) and had longer residence times within the rat esophagus in vivo. Incubation with human esophagus (Het-1A) cells confirmed BNPs' biocompatibility at clinically relevant concentrations. In a rat model of achalasia, nifedipine-loaded BNPs significantly enhanced esophageal drug exposure, increased therapeutic efficacy, and reduced systemic drug exposure compared to NNPs and free drug. The safety of BNPs was demonstrated by an absence of intestinal, hepatic, and splenic toxicity following administration. This study is the first to demonstrate the efficacy of BNPs for esophageal drug delivery and highlight their potential for improving the lives of patients suffering with esophageal conditions.

Novel drug delivery systems and disease models for pulmonary fibrosis.

Pulmonary fibrosis (PF) is a serious and progressive lung disease which is possibly life-threatening. It causes lung scarring and affects lung functions including epithelial cell injury, massive recruitment of immune cells and abnormal accumulation of extracellular matrix (ECM). There is currently no cure for PF. Treatment for PF is aimed at slowing the course of the disease and relieving symptoms. Pirfenidone (PFD) and nintedanib (NDNB) are currently the only two FDA-approved oral medicines to slow down the progress of idiopathic pulmonary fibrosis, a specific type of PF. Novel drug delivery systems and therapies have been developed to improve the prognosis of the disease, as well as reduce or minimize the toxicities during drug treatment. The drug delivery routes for these therapies are various including oral, intravenous, nasal, inhalant, intratracheal and transdermal; although this is dependent on specific treatment mechanisms. In addition, researchers have also expanded current animal models that could not fully restore the clinicopathology, and developed a series of in vitro models such as organoids to study the pathogenesis and treatment of PF. This review describes recent advances on pathogenesis exploration, classifies and specifies the progress of drug delivery systems by their delivery routes, as well as an overview on the in vitro and in vivo models for PF research.

Quantitative evaluation of ecological compensation policies for the watershed in China: based on the improved Policy Modeling Consistency Index.

Ecological compensation policies for the watershed (ECPW) have played a guiding role in establishing a sound watershed ecological compensation system with Chinese characteristics, and the quantitative evaluation of current policies can provide a reference for policy optimization. Firstly, taking 77 ECPW promulgated in China from 2006 to 2020 as the research objects, this paper extracted keyword frequencies using a text mining method, and then selected the policy indicators by combining the policy characteristics and existing results of watershed ecological compensation. Secondly, the Fuzzy analytic hierarchy process was used to determine the weights of the variables and improve the Policy Modeling Consistency Index (PMC-Index). Finally, the empirical analysis was conducted on six typical policies and the differences among P1, P3, and P5 at the three levels of the national, provincial, and municipal levels were further explored and compared. It was found that (1) the consistency evaluation of P1, P2, P3, and P4 were excellent levels, and that of P5 and P6 were acceptable levels. (2) The mean value of an improved PMC-Index of the six strategies was 0.6287, which indicated that the overall performance of the quality of ECPW was good, but still room for improvement. (3) The quality of China's ECPW showed a trend that the higher the level of government, the better the overall performance of the policy. The more targeted the ECPW, the lower the PMC index score, which is manifested in indicators such as incentive measures, policy mechanisms, policy areas, and policy functions. This study helps to fully understand the strengths and weaknesses of China's single ECPW.