Current status and influencing factors of policy identification in health impact assessment: a case study of Zhejiang Province.

BACKGROUND: Health impact assessment (HIA) is a procedure, method and tool for evaluating the potential health impacts of policies, plans and construction projects, as well as the distribution of these impacts on population. Majority of international studies on health impact assessment have focussed on conceptual papers or case evaluations, neglecting participants' views on policies. METHODS: A semi-structured interview with 30 health impact assessment experts was employed in this study, and the Nvivo software was utilized to analyse factors that influence policy identification. Subsequently, a multi-stage stratified random sampling method was adopted to survey 655 pilot staff members involved in health impact assessment in Zhejiang Province. Descriptive statistics were used to describe the current status and identify the factors influencing policy identification. In addition, hierarchical linear regression analysis and structural equation modelling were employed to determine the relationship between policy identification and influencing factors. RESULTS: Statistically significant differences were found among participants in the level of identification of policies across three dimensions. The policy sentiment dimension had the highest score (4.137 ± 0.664), followed by policy cognition (4.075 ± 0.632) and policy evaluation (3.631 ± 0.797) dimensions. Subject trust had a positive impact on policy cognition (ß = 0.503, P < 0.001), policy sentiment (ß = 0.504, P < 0.001) and policy evaluation (ß = 0.465, P < 0.001). Procedural justice had a positive impact on policy sentiment (ß = 0.085, P < 0.01) and policy evaluation (ß = 0.084, P < 0.05), but not policy cognition (ß = 0.056, P > 0.05). Policy identification is influenced by age and average monthly salary among other factors. CONCLUSION: These results highlight the importance of subjective trust and procedural justice in policy identification of health impact assessment. They provide valuable insights to developing interventions to overcome barriers to the implementation and enhancement of global identification of policies. Going forward, cross-sectoral synergies, enhanced international communication and training to increase participants' trust in the policy should be optimized to improve health impact assessment. Additional measures should be taken, such as ensuring seamless communication channels, embedding health impact assessment in administrative mechanisms, and establishing strong oversight and grievance mechanisms to improve fairness and transparency in the implementation and results of health impact assessment.

Guanxinning tablets improve myocardial hypertrophy by inhibiting the activation of MEK-ERK1/2 signaling pathway.

Myocardial hypertrophy may lead to heart failure and sudden death. As traditional Chinese medicine, Guanxinning tablets (GXN) have significant pharmacological effects in the prevention and treatment of cardiovascular diseases. However, the anti-cardiac hypertrophy efficacy of GXN and its mechanism of action are still unclear. Therefore, we established a heart failure rat model and isolated primary cardiomyocytes of neonatal rat to observe the protective effect of GXN on heart failure rat model and the intervention effect on myocardial cell hypertrophy, and to explore the possible mechanism of GXN preventing and treating myocardial hypertrophy. The results of in vivo experiments showed that GXN could significantly reduce the degree of cardiac hypertrophy, reduce the size of cardiomyocytes, inhibit the degree of myocardial remodeling and fibrosis, and improve cardiac function in rats with early heart failure. The results of in vitro experiments showed that GXN was safe for primary cardiomyocytes and could improve cardiomyocyte hypertrophy and reduce the apoptosis of cardiomyocytes in pathological state, which may be related to the inhibition of the over-activation of MEK-ERK1/2 signaling pathway. In conclusion, GXN may inhibit cardiac hypertrophy and improve early heart failure by inhibiting the over-activation of MEK-ERK1/2 signaling pathway.

Case Series: Application of Topography-guided Contoura Refractive Surgery in Highly Irregular Cornea.

SIGNIFICANCE: Highly irregular cornea leads to poor vision, glare, and starbursts. Although treatment is still at the exploration stage, topography-guided Contoura surgery has excellent potential for the treatment of highly irregular corneas. PURPOSE: This case series reviews three patients (one with abnormal back elevation, one with corneal scar after fungal keratitis, and one with post-laser-assisted in situ keratomileusis central islands) treated with topography-guided Contoura surgery. CASE REPORTS: In case 1, a 19-year-old man underwent topography-guided Contoura refractive surgery in the left eye and wavefront-optimized ablation in the right eye. Post-operative topography of the right eye showed marked inferior steepening and central irregular astigmatism compared with the contralateral eye. In case 2, a 53-year-old man presented with corneal scarring on the right eye after recovering from fungal keratitis. The patient first underwent phototherapeutic keratectomy and photorefractive keratectomy to remove the scarring primarily. He then underwent Contoura to correct hyperopia, which flattened the cornea and improved his vision significantly. In case 3, a 25-year-old man presented with central steepening on topography maps after undergoing laser-assisted in situ keratomileusis. He underwent topography-guided ablation, which improved his visual acuity and normalized the cornea. CONCLUSIONS: Therapy for highly irregular corneas includes wavefront-guided surgery, conservative treatment, corneal transplantation, rigid gas-permeable lenses, and so on. In this case series, topography-guided Contoura refractive surgery provided an excellent option for reducing topographic abnormalities and improving vision.

Rod-Shaped Micelles Based on PHF- g-(PCL-PEG) with pH-Triggered Doxorubicin Release and Enhanced Cellular Uptake.

A biodegradable brush-type copolymer PHF- g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.

Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and Photorefractive Keratectomy for Corneal Ectasia after Laser in situ Keratomileusis.

PURPOSE: The aim of this study was to analyze the effects of corneal crosslinking (CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) in halting the progression and improving the visual function of corneal ectasia after laser in situ keratomileusis (LASIK). METHODS: PTK-PRK-CXL was performed on 14 eyes of 14 patients who developed corneal ectasia after LASIK. The visual acuity, spherical refraction and cylinder, corneal topography indices, thinnest corneal thickness (TCT), and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: The mean uncorrected visual acuity improved significantly from 0.64 ± 0.36 logMAR preoperatively to 0.19 ± 0.12 logMAR at 12 months of follow-up (p < 0.001), while the mean best corrected visual acuity improved from 0.21 ± 0.14 logMAR at baseline to 0.04 ± 0.10 logMAR at 12 months postoperatively (p < 0.001). A significant decrease was observed in Kmax and Kmean values from 52.51 ± 6.74 and 43.55 ± 3.37 D at baseline to 45.72 ± 5.18 (p < 0.001) and 40.60 ± 3.05 D (p < 0.001) at the 1-year follow-up. The mean TCT decreased significantly from 419.07 ± 36.56 µm before treatment to 320.93 ± 39.78 µm at 12 months of follow-up (p < 0.001), and there was no significant endothelial cell loss (p > 0.05) beyond 6 months after treatment. CONCLUSION: PTK-PRK-CXL is a promising procedure to halt the progression of post-LASIK keratectasia with significant visual quality improvement.

Clinical Study of Mitomycin C in Reducing Haze Formation After Ultraviolet A/Riboflavin Crosslinking for Keratoconus.

OBJECTIVES: To evaluate the safety and efficacy of mitomycin C (MMC) in haze formation after ultraviolet A/riboflavin corneal crosslinking (CXL) for progressive keratoconus. METHODS: A total of 60 keratoconic eyes of 48 patients were enrolled in this prospective comparative study after obtaining informed consent. In the CXL group, standard corneal CXL was performed, whereas in the CXL+MMC group, 0.02% MMC was used for 30 s soon after CXL. Comprehensive ophthalmologic examinations were performed on all patients before surgery and at 1, 3, 6, and 12 months after surgery. RESULTS: The epithelium recovered within 3 to 4 days after CXL, and the healing time was comparable in the two groups. There was no significant endothelial cell density loss after CXL in both groups. Eyes in both groups showed improvement of uncorrected distance visual acuity (Snellen) and best-corrected visual acuity (Snellen; P<0.05), and there was a decrease in K-max, cylinder degree, and central corneal thickness (CCT) (P<0.05). There was no significant statistical difference between the groups regarding postoperative K-max reduction, refraction, and CCT (P>0.05). Corneal haze scores were significantly higher in the CXL group at 1 and 3 months after CXL (P=0.012 and P=0.028, respectively), but were similar to the MMC group at 6 and 12 months after surgery (P=0.329 and P=0.543, respectively). CONCLUSIONS: Prophylactic intraoperative use of 0.02% MMC can significantly reduce CXL-associated haze formation, especially in the early postoperative period, and no signs of weakening CXL efficacy were observed.

The Evaluation of Corneal Fragility After UVA/Riboflavin Crosslinking.

PURPOSE: To evaluate the fragility of cornea after UVA/riboflavin crosslinking (CXL). METHODS: Sixty New Zealand rabbits received UVA/riboflavin crosslinking treatment (wavelength 365 nm, irradiance 3.0 mW/cm, and total dose 5.4 J/cm) on right eyes. Animals were sacrificed before and immediately after treatment (day 0), day 1, 3, 7, and 28 after treatment. A 4×10 mm corneal strip for biomechanical evaluation was harvested after sacrifice. The corneal fragility was evaluated by measurement of elongation rate, whereby the elongation rate equals elongation length/baseline length. RESULTS: The Youngs modulus and maximal stress were 1.41±0.51 MPa and 5.56±1.84 MPa before CXL, and increased to 2.31±0.68 MPa (P=0.008) and 9.25±2.74 MPa (P=0.04), respectively, on day 0, then maintained a stable level within a 28 days follow-up. The elongation rate was 62.04±9.34% before CXL and decreased to 48.95%±8.24% (P=0.02) on day 0, then maintained a stable level within a 28 days follow-up. CONCLUSIONS: This study showed an increase in the corneal fragility after UVA/riboflavin crosslinking along with an increase in the corneal stiffness. A long-term follow-up should be taken to evaluate the potential deleterious effect of the increasing corneal fragility after UVA/riboflavin crosslinking.

Preparation of intravenous injection nanoformulation via co-assemble between cholesterylated gemcitabine and cholesterylated mPEG: enhanced cellular uptake and intracellular drug controlled release.

The objective of this study was to prepare the CHS-mPEG/CHS-dFdC nanoformulation could be administrated through intravenous injection in nude mice. Particularly, CHS-mPEG was selected to co-assemble with CHS-dFdC to improve the prodrug concentration and enhance the stability of nanoformulation. The nanoformulation could be prepared by codissolution-coprecipitation. All of the nanoformulations kept stable in PBS at 4 °C or simulative human plasma at 37 °C. As molar ratios of CHS-mPEG1900/CHS-dFdC increased from 0.1/1 to 2/1, the weight concentration of CHS-dFdC increased from 2.5 to 15 mg/mL. It was found the optimal CHS-mPEG1900/CHS-dFdC nanoformulation displayed controlled drug release in simulative lysosome condition. The amount of released dFdC reached up to 90% within 10 h. It also exhibited enhanced cellular uptake ability, 7-folds higher than that of dFdC during 2.5 h incubation. And it showed superior cytotoxicity resulted from the enhanced cellular uptake ability on BxPC-3 cells.

Comparative Study on the Satisfaction of Healthcare Service Providers with the Synergistic Development of Rural Healthcare Systems in China: Medical Alliance Counties vs. Non-Medical Alliance Counties.

Introduction: This study aimed to explore whether the establishment of county medical alliances can improve satisfaction with the vertical integration of healthcare systems among rural medical and healthcare service provider managers and service providers. Our study also sought to provide recommendations for the sustainable development of vertical integration in healthcare systems. Methods: A semi-structured interview with 30 healthcare service providers was employed in this research, and Nvivo software was utilized to analyze factors that influence vertical integration. From April to July 2021, a multi-stage random sampling method was used to select participants. The sample included two leading hospitals in medical consortia, 15 member units (healthcare service providers and medical staff), two county-level hospitals, and 15 township health centers/community healthcare service centers from non-medical consortia. Questionnaire surveys were conducted with these groups. Factor analysis was used to calculate satisfaction scores for healthcare service providers with the cross-institutional synergistic development of healthcare systems in both medical and non-medical consortia (denoted as M(IQR)). Propensity score matching was employed to reduce confounding factors between groups. The Mann-Whitney U test was used to compare satisfaction differences between groups. Results: The overall satisfaction scores for lead-county hospital managers, member institution managers, medical staff at the lead-county hospital, and medical staff at member institutions were 4.80 (1.00), 4.17 (1.17), 4.00 (1.38), and 4.00 (1.12), respectively. Lead-county hospital managers' satisfaction with cross-institutional collaboration, development capacity enhancement, and structure and resource integration in the Medical Alliance group showed higher satisfaction than the Non-Medical Alliance. Similarly, lead-county hospital medical staff in the Medical Alliance group reported greater satisfaction with collaboration efforts, supportive environment, and development capacity enhancement. Notably, while the Medical Alliance group's satisfaction scores were higher, the differences between the two groups were not statistically significant for lead-county hospital managers and medical staff. The Medical Alliance group did show statistically significant differences in member institution managers' satisfaction with collaboration, development capacity enhancement, and structure and resource integration. Additionally, medical staff of member institutions in the Medical Alliance group reported statistically significant higher satisfaction with collaboration, supportive environment, development capacity enhancement, healthcare service integration, and human resource development. Conclusion: To facilitate the establishment of county medical alliances, managers of leading county-level hospitals should adopt a healthcare system integration strategy. This strategy involves evolution from being a member of a single institution to a coordinator of cross-institutional vertical integration of medical and healthcare services. Additionally, revamping remuneration and appraisal systems for members of county medical alliances is necessary. This will encourage cooperation among healthcare institutions within the three-tiered system and their medical staff, ultimately facilitating the provision of integrated services.

Effects of Social Networks on Job Performance of Individuals among the Hypertension Management Teams in Rural China.

BACKGROUND: Limited studies have explored the relationship among cross-organizational and multidisciplinary medical staff. AIM: The present study conducted an in-depth examination and validation of the influence of complex cross-organization and multidisciplinary social networks on the job performance of team members. METHOD: Multi-level hierarchical regression analysis was used to assess the impact of the centrality and the characteristics of structural holes in social networks (i.e., advice network, information network, friendship network, and trust network) on job performance. RESULTS: The in-closeness centrality of the advice network (ß = 0.176, p < 0.05) and the betweenness centrality of the trust network (ß = 0.126, p < 0.05) had positive effects on task performance. The in-closeness centrality of the advice network (ß = 0.226, p < 0.05; ß = 0.213, p < 0.05) and the CI (1 - constraint index) of the friendship network (ß = 0.130, p < 0.05; ß = 0.132, p < 0.05) had positive effects on contextual performance and overall job performance. Meanwhile, the out-closeness centrality of the information network (ß = -0.368, p < 0.01; ß = -0.334, p < 0.05) had a negative effect on contextual performance and overall job performance. CONCLUSIONS: This study investigates the relationship between healthcare professionals' job performance and their social networks, taking into account the perspectives of cross-organizational and multidisciplinary teams. The study contributes to the effort of breaking down barriers between different disciplines and organizations, and ultimately, improving the quality of healthcare delivery.

Effects of the Two-Dimensional Structure of Trust on Patient Adherence to Medication and Non-pharmaceutical Treatment: A Cross-Sectional Study of Rural Patients With Essential Hypertension in China.

In rural China, treatment adherence of patients with hypertension remains a challenge. Although early research on patient adherence has confirmed the importance of trust in doctors, the relative contribution and influence of the two-dimensional structure of trust on adherence has not been explored. Thus, this study examined the effects of patient trust in primary care physicians' (PCPs) benevolence and ability on medication adherence, dietary management, and physical activity. The data were derived from 2,533 patients at 54 primary health institutions in China (village level) from February 2017 to May 2018. Participants were assessed using the Chinese version of the Wake Forest Physician Trust Scale and the Therapeutic Adherence Subscale for Hypertensive Patients. Other information included region, gender, age, and self-rated health status. The results of multiple linear regression and structural equation modeling confirmed that patient trust in PCPs' benevolence was positively correlated with patient adherence to medication, diet management, and physical activity. Patient trust in PCPs' ability was negatively correlated with adherence to dietary management and physical activity. We concluded that interventions aimed at increasing PCP benevolence have the greatest potential to improve patient adherence to hypertension treatment. Under the country's policy of advocating to improve PCPs' diagnoses and treatment technology, it may be important to cultivate doctors' communication skills, medical ethics, and other benevolent qualities to improve patients' adherence with drug and Non-drug treatments.

The complete chloroplast genome of Calohypnum plumiforme (Wilson) (hypanceae, bryophyta).

Calohypnum plumiforme is a widely distributed moss in East Asia. In this study, Illumina sequencing data was used to assemble the complete chloroplast genome of C. plumiforme. The length of the circular genome is 124,037 bp. It contains a total of 121 genes, including 81 protein-coding, 36 tRNA, and 4 rRNA genes. The GC content of the chloroplast genome of C. plumiforme is 29.07%. The phylogenetic analysis suggested that C. plumiforme is sister to Calliergonella cuspidata. This study provides important sequence information for species identification and its phylogenetic relationship in the Bryopsida.

Guanxinning Tablet Attenuates Coronary Atherosclerosis via Regulating the Gut Microbiota and Their Metabolites in Tibetan Minipigs Induced by a High-Fat Diet.

Coronary atherosclerosis (CA) is a chronic and evolving inflammatory disease characterized by the build-up of atherosclerotic plaque in the wall of coronary arteries. Guanxinning tablet (GXNT) is a novel Chinese medicine formula, which has been clinically used to treat coronary heart disease for many years. However, the potential mechanism for treating CA remains unclear. Thus, the study was aimed at investigating the therapeutic effect of GXNT on CA and further explore the underlying mechanisms from the perspective of gut microbiota. Following the establishment of a CA model in Tibetan minipigs, GXNT was orally administrated. We simultaneously detected blood lipid levels, observed ventricular function using ultrasound examination, measured platelet aggregation, and checked changes in inflammatory factors, oxidative stress factors, and vascular endothelial injury-related indexes applying ELISA assays. Histopathological changes of coronary artery tissue were subsequently evaluated using Sudan IV staining, HE staining, Oil red "O" staining, and immunohistochemistry assays. Finally, alterations of the gut microbiota and microbial metabolites were detected using metagenomic sequencing and targeted metabolomics, respectively. The results have suggested that GXNT could regulate dyslipidemia, improve heart function, and inhibit the levels of ox-LDL, CRP, TNF-α, IL-1ß, SOD, MDA, vWF, and ET-1, as well as platelet aggregation. Additionally, histopathological findings revealed that GXNT could reduce lipid deposition, alleviate AS lesions, and restrain the expressions of NF-κB, TNF-α, and MMP-9. Furthermore, the composition of the gut microbiota was altered. Specifically, GXNT could upregulate the relative abundance of Prevotellaceae and Prevotella and downregulate the abundance of Proteobacteria, Enterobacteriaceae, and Escherichia. As for microbial metabolites, GXNT could increase fecal propionic acid, butyric acid, and LCA-3S and decrease fecal TMA-related metabolites, CDCA, and serum TMAO. In sum, the results showed that GXNT had a satisfactory anti-CA effect, and the mechanism was closely associated with modulating gut microbiota and related metabolites.

Guanxinning tablet inhibits the interaction between leukocyte integrin Mac-1 and platelet GPIbα for antithrombosis without increased bleeding risk.

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.

Redox sensitive nano-capsules self-assembled from hyaluronic acid-hydroxychloroquine conjugates for CD44-targeted delivery of hydroxychloroquine to combat breast cancer metastasis in vitro and in vivo.

Identifying an efficient tumor-targeted drug delivery system is an urgent task for the treatment of metastatic breast cancer. Herein, we report for the first time that a pH and redox dual-responsive polymer prodrug displays prominent inhibition of breast cancer metastasis to the lung. The polymer molecule was synthesized from hyaluronic acid (HA) and hydroxychloroquine (HCQ) through disulfide bonds as redox-sensitive linkers that self-assemble into nanocapsules (HA-ss-HCQ nanocapsules) at pH 7.4. Due to the pKa value of HCQ and built-in disulfide bonds, the nanocapsules were endowed with pH and redox dual-responsive properties. The in vitro drug release curve revealed that HA-ss-HCQ nanocapsules release drugs more quickly under low pH and high redox conditions. Moreover, the nanocapsules displayed active targeting and selectivity to metastatic breast cancer cells. Cellular uptake of Nile red-loaded nanocapsules observed by fluorescence microscopy showed that the nanocapsules exerted significantly enhanced cellular internalization capacity, which was greatly diminished by free HA. The IC50 of HA-ss-HCQ nanocapsules in 4T1 cells was 2.23-fold lower than that of free HCQ. Importantly, wound healing assays and Transwell experiments demonstrated that HA-ss-HCQ nanocapsules greatly inhibited the migration and invasion of 4T1 cells. In particular, the metastasis of 4T1 cells to the lung was also remarkably suppressed by HA-ss-HCQ nanocapsules with minimal toxicity in an in vitro lung metastasis model, which was verified by the detection of macroscopic metastatic nodules and histological examination. In summary, this study provides a promising strategy for active-targeting therapy in metastatic breast cancer.

The influence of the choroid on the onset and development of myopia: from perspectives of choroidal thickness and blood flow.

Myopia is the most common type of refractive errors characterized by excessive elongation of the ocular globe. With the increasing prevalence of myopia, improved knowledge of factors involved in myopia development is of particular importance. There are growing evidence suggesting that the choroid plays an important role in the regulation of eye growth and the development of myopia. Studies have demonstrated that thinning choroid is a structural feature of myopia, with a negative correlation between choroidal thickness and axial length, suggesting that the change in choroidal thickness may be a predictive biomarker for long-term changes in ocular elongation. Given the fact that the choroid is primarily a vascular structure capable of rapidly changing blood flow, variations of choroidal thickness might be primarily caused by changes in choroidal blood flow. Considering that hypoxia is associated with myopia and choroidal blood flow is the main source of oxygen and nourishment supply, apart from the effect on myopia possibly by changing choroidal thickness, decreasing choroidal blood flow may contribute to scleral ischaemia and hypoxia, resulting in alterations in the scleral structure and thus leading to myopia. This review aims to provide an overview of recent work exploring the influence of the choroid on myopia from perspectives of choroidal thickness and blood flow, which may present new predictive indicators for the onset of myopia and new targets for the development of novel therapeutic approaches for myopia.

Seed germination ecology of Conyza sumatrensis populations stemming from different habitats and implications for management.

Conyza sumatrensis (Retz.) E. H. Walker is an obnoxious weed, emerging as an invasive species globally. Seed germination biology of four populations of the species stemming from arid, semi-arid, temperate, and humid regions was determined in this study. Seed germination was recorded under six different environmental cues (i.e., light/dark periods, constant and alternating day and night temperatures, pH, salinity, and osmotic potential levels) in separate experiment for each cue. Populations were main factor, whereas levels of each environmental cue were considered as sub-factor. The impact of seed burial depths on seedling emergence was inferred in a greenhouse pot experiment. Seed germination was recorded daily and four germination indices, i.e., seed germination percentage, mean germination time, time to reach 50% germination, and mean daily germination were computed. Tested populations and levels of different environmental cues had significant impact on various seed germination indices. Overall, seeds stemming from arid and semi-arid regions had higher seed germination potential under stressful and benign environmental conditions compared to temperate and humid populations. Seed of all populations required a definite light period for germination and 12 hours alternating light and dark period resulted in the highest seed germination. Seed germination of all populations occurred under 5-30°C constant and all tested alternate day and night temperatures. However, the highest seed germination was recorded under 20°C. Seeds of arid and semi-arid populations exhibited higher germination under increased temperature, salinity and osmotic potential levels indicating that maternal environment strongly affected germination traits of the tested populations. The highest seed germination of the tested populations was noted under neutral pH, while higher and lower pH than neutral had negative impact on seed germination. Arid and semi-arid populations exhibited higher seed germination under increased pH compared to temperate and humid populations. Seed burial depth had a significant effect on the seedling emergence of all tested populations. An initial increase was noted in seedling emergence percentage with increasing soil depth. However, a steep decline was recorded after 2 cm seed burial depth. These results indicate that maternal environment strongly mediates germination traits of different populations. Lower emergence from >4 cm seed burial depth warrants that deep burial of seeds and subsequent zero or minimum soil disturbance could aid the management of the species in agricultural habitats. However, management strategies should be developed for other habitats to halt the spread of the species.

GuanXinNing Tablet Attenuates Alzheimer's Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits.

Based on accumulating evidence, Alzheimer's disease (AD) is related to hypercholesterolemia, gut microbiota, and host metabolites. GuanXinNing Tablet (GXN) is an oral compound preparation composed of two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., both of which exert neuroprotective effects. Nevertheless, the effect of GXN on AD is unknown. In the present study, we investigated whether GXN alters cholesterol, amyloid-beta (Aß), gut microbiota, serum metabolites, oxidative stress, neuronal metabolism activities, and apoptosis in an AD model rabbit fed a 2% cholesterol diet. Our results suggested that the GXN treatment significantly reduced cholesterol levels and Aß deposition and improved memory and behaviors in AD rabbits. The 16S rRNA analysis showed that GXN ameliorated the changes in the gut microbiota, decreased the Firmicutes/Bacteroidetes ratio, and improved the abundances of Akkermansia and dgA-11_gut_group. 1H-NMR metabolomics found that GXN regulated 12 different serum metabolites, such as low-density lipoprotein (LDL), trimethylamine N-oxide (TMAO), and glutamate (Glu). In addition, the 1H-MRS examination showed that GXN remarkably increased N-acetyl aspartate (NAA) and Glu levels while reducing myo-inositol (mI) and choline (Cho) levels in AD rabbits, consequently enhancing neuronal metabolism activities. Furthermore, GXN significantly inhibited oxidative stress and neuronal apoptosis. Taken together, these results indicate that GXN attenuates AD via improving gut microbiota, host metabolites, and neuronal apoptosis.

Poly(ethylene glycol) shell-sheddable TAT-modified core cross-linked nano-micelles: TAT-enhanced cellular uptake and lysosomal pH-triggered doxorubicin release.

This study aimed to develop sheddable polyethylene glycol (PEG) shells with TAT-modified core cross-linked nanomicelles as drug-delivery carriers of doxorubicin (DOX) to establish a programmed response against the tumor microenvironment, enhanced endocytosis, and lysosomal pH-triggered DOX release. First, poly(L-succinimide) (PSI) underwent a ring-opening reaction with ethylenediamine to generate poly(N-(2-aminoethyl)-l-aspartamide) (P(ae-Asp)). Next, the thiolytic cleavable PEG, 3,4-dihydroxyphenylacetic acid, and TAT were grafted onto P(ae-Asp) to synthesize the amphiphilic graft copolymer of mPEG-SS-g-P(ae-Asp)-MCA-DA-TAT. In aqueous solution, the amphiphilic polymer self-assembled into nanomicelles, encapsulating DOX into the hydrophobic core of micelles. TAT was shielded by the PEG corona during circulation to avoid non-specific transmembrane interaction with normal cells, while the tumor redox environment-responsive shedding of PEG could expose TAT to promote internalization of tumor cells. In order to improve the stability of nanomicelles and achieve pH-triggered drug release, a core cross-linking strategy based on the coordination of catechol and Fe3+ was adopted. In vitro studies demonstrated that core cross-linked nanomicelles maintained the nanostructure in 100 times dilution in pH 7.4 phosphate-buffered saline (PBS). Moreover, DOX release from DOX-loaded core cross-linked nanomicelles (DOX-TAT-CCLMs) was favored at simulated lysosomal conditions over simulated plasma conditions, indicating that these nanomicelles demonstrate characteristics of pH-triggered DOX release. The TAT modification considerably enhanced the mean fluorescence intensity of the nanomicelles endocytosed by MCF-7/ADR cells by 8 times, compared with DOX·HCl after 8 h of incubation. Notably, the IC50 value of nanomicelles (11.61 ±â€¯0.95 µg/mL) was nearly 4 times lower than that of DOX·HCl against MCF-7/ADR cells, implying that the nanomicelles could overcome drug resistance observed in MCF-7/ADR cells. Furthermore, the DOX-TAT-CCLMs reported superior tumor growth suppression in a 4T1 tumor-bearing mouse model. Thus, the redox- and pH- stimuli stepwise-responsive novel nanomicelles fabricated from the mPEG-SS-g-P(ae-Asp)-MCA-DA-TAT graft copolymer exhibited multifunctionality and displayed great potential for drug delivery.

Dynamic core crosslinked camptothecin prodrug micelles with reduction sensitivity and boronic acid-mediated enhanced endocytosis: An intelligent tumor-targeted delivery nanoplatform.

The physicochemical properties of camptothecin (CPT) limit its clinical application. To maximize drug efficacy, a novel intelligent prodrug delivery nanoplatform with a tumor microenvironment-cleavable core crosslinking strategy was proposed based on a phenylboronic acid (PBA) modified polyethylene glycol (PEG)-polyglutamic acid (PGlu) polymer with disulfide-bonded CPT, called PBA-PEG-P(Glu-co-GlussCPT). The fabricated nanoplatform was a spherical micelle that could withstand dilution and carry a large number of therapeutic molecules to the tumor tissues, thereby minimizing premature drug release. Moreover, the nanoplatform release 6.2 ± 0.62, 12.4 ± 1.8, 46.7 ± 0.33, and 79.2 ± 1.58% of CPT after incubation in 0.02, 1, 5, and 10 mM dithiothreitol for 24 h, respectively, exhibiting good reduction-sensitivity. Moreover, the nanoplatform exhibited significant antiproliferative activity against tumor cells. In addition, with PBA modification, the nanoplatform demonstrated enhanced endocytosis efficiency. This prodrug nanoplatform also exhibited significant in vivo antitumor efficacy on both murine and human hepatoma xenograft models, without showing significant systemic toxicity but demonstrating good biocompatibility. In other words, this novel intelligent prodrug delivery nanoplatform with tumor microenvironment-cleavable core crosslinking strategy and active targeting strategy based on prodrug polymer PBA-PEG-P(Glu-co-GlussCPT) demonstrated multiple functions and significant potential for antitumor drug delivery.