The Effect of Psychological Intervention on the Visual Quality of Patients with a Diffractive Multifocal Intraocular Lens Implant.

OBJECTIVE: This study aimed to investigate the effect of psychological intervention on the visual quality of patients with a diffractive multifocal intraocular lens implant and its possible mechanism. METHODS: Eighty-nine patients undergoing age-related cataract surgery were enrolled in the study at the Affiliated Hospital of Southwest Medical University between December 2015 and July 2017. They were randomly divided into two groups: multiple focus M1 group (n = 45) and multiple focus M2 group (n = 40). The M1 group was only given routine preoperative health education, treatment, and evaluation, while the M2 group also received psychological intervention. RESULTS: After treatment, there was no statistical difference in the uncorrected distance and near visual acuity, corrected distance and near visual acuity, or the vision and near removal rate in either of the two groups (p > 0.05). However, postoperative glare was lower in the M2 group (p < 0.05), and patient satisfaction was higher in the M2 group (p < 0.05). The M2 group had a more obvious improvement in the Symptom Checklist-90 score (p < 0.05), the serum interleukin-6 (IL-6) was lower, and the serum brain-derived neurotrophic factor (BDNF) was higher in the M2 group (p < 0.05). In addition, serum IL-6 had a negative correlation with the depression score, and serum BDNF also showed a negative correlation with the anxiety score (p < 0.05). CONCLUSIONS: Psychological intervention improved the stress state of patients with age-related cataracts and diffractive multifocal intraocular lens implants, reduced the level of inflammatory factors in the body, improved the level of BDNF, reduced postoperative visual interference, and improved postoperative satisfaction.

Impacts of Urban Blue-Green Space on Residents' Health: A Bibliometric Review.

Urban blue-green space (UBGS), as an important component of the urban environment, is found to closely relate to human health. An extensive understanding of the effects of UBGS on human health is necessary for urban planning and intervention schemes towards healthy city development. However, a comprehensive review and discussion of relevant studies using bibliometric methods is still lacking. This paper adopted the bibliometric method and knowledge graph visualization technology to analyze the research on the impact of UBGS on residents' health, including the number of published papers, international influence, and network characteristics of keyword hotspots. The key findings include: (1) The number of articles published between 2001 and 2021 shows an increasing trend. Among the articles collected from WoS and CNKI, 38.74% and 32.65% of the articles focus on physical health, 38.32% and 30.61% on mental health, and 17.06% and 30.61% on public health, respectively. (2) From the analysis of international partnerships, countries with high levels of economic development and urbanization have closer cooperation than other countries. (3) UBGS has proven positive effects on residents' physical, mental, and public health. However, the mediating effects of UBGS on health and the differences in the health effects of UBGS on different ages and social classes are less studied. Therefore, this study proposes several future research directions. First, the mediating effect of UBGS on health impacts should be further examined. Furthermore, the interactive effects of residents' behaviors and the UBGS environment should be emphasized. Moreover, multidisciplinary integration should be strengthened. The coupling mechanism between human behavior and the environment should also be studied in depth with the help of social perception big data, wearable devices, and human-computer interactive simulation. Finally, this study calls for developing health risk monitoring and early warning systems, and integrating health impact assessment into urban planning, so as to improve residents' health and urban sustainability.

New insight into DAVF pathology-Clues from meningeal immunity.

In recent years, with the current access in techniques, studies have significantly advanced the knowledge on meningeal immunity, revealing that the central nervous system (CNS) border acts as an immune landscape. The latest concept of meningeal immune system is a tertiary structure, which is a comprehensive overview of the meningeal immune system from macro to micro. We comprehensively reviewed recent advances in meningeal immunity, particularly the new understanding of the dural sinus and meningeal lymphatics. Moreover, based on the clues from the meningeal immunity, new insights were proposed into the dural arteriovenous fistula (DAVF) pathology, aiming to provide novel ideas for DAVF understanding.

Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model.

Tremendous progress has been made in the field of nanomedicine for cancer treatment. However, most of the research to date has been focused on inhibiting primary tumor growth with comparatively less efforts directed towards managing tumor metastasis. Here, we introduce a polymeric conjugate P-DOX-iRGD that not only significantly suppressed primary tumor growth but also substantially inhibited pulmonary metastasis in an orthotopic mouse model of breast cancer. In addition, treatment with P-DOX-iRGD markedly reduced breast cancer-induced splenomegaly and liver hematopoiesis. Interestingly, contrasting results were seen for the free form and polymeric form of DOX in vitro and in vivo, which may be attributed to the enhanced permeability and retention (EPR) effect.

Cerebral Cavernous Malformation: Immune and Inflammatory Perspectives.

Cerebral cavernous malformation (CCM) is a type of vascular anomaly that arises due to the dyshomeostasis of brain capillary networks. In the past two decades, many advances have been made in this research field. Notably, as a more reasonable current view, the CCM lesions should be attributed to the results of a great number of additional events related to the homeostasis disorder of the endothelial cell. Indeed, one of the most fascinating concerns in the research field is the inflammatory perturbation in the immune microenvironment, which would affect the disease progression as well as the patients' outcomes. In this work, we focused on this topic, and underlined the immune-related factors' contribution to the CCM pathologic progression.

Correlation Analysis between Urban Elements and COVID-19 Transmission Using Social Media Data.

The outbreak of the COVID-19 has become a worldwide public health challenge for contemporary cities during the background of globalization and planetary urbanization. However, spatial factors affecting the transmission of the disease in urban spaces remain unclear. Based on geotagged COVID-19 cases from social media data in the early stage of the pandemic, this study explored the correlation between different infectious outcomes of COVID-19 transmission and various factors of the urban environment in the main urban area of Wuhan, utilizing the multiple regression model. The result shows that most spatial factors were strongly correlated to case aggregation areas of COVID-19 in terms of population density, human mobility and environmental quality, which provides urban planners and administrators valuable insights for building healthy and safe cities in an uncertain future.

Estimating Unreported COVID-19 Cases with a Time-Varying SIR Regression Model.

BACKGROUND: Potential unreported infection might impair and mislead policymaking for COVID-19, and the contemporary spread of COVID-19 varies in different counties of the United States. It is necessary to estimate the cases that might be underestimated based on county-level data, to take better countermeasures against COVID-19. We suggested taking time-varying Susceptible-Infected-Recovered (SIR) models with unreported infection rates (UIR) to estimate factual COVID-19 cases in the United States. METHODS: Both the SIR model integrated with unreported infection rates (SIRu) of fixed-time effect and SIRu with time-varying parameters (tvSIRu) were applied to estimate and compare the values of transmission rate (TR), UIR, and infection fatality rate (IFR) based on US county-level COVID-19 data. RESULTS: Based on the US county-level COVID-19 data from 22 January (T1) to 20 August (T212) in 2020, SIRu was first tested and verified by Ordinary Least Squares (OLS) regression. Further regression of SIRu at the county-level showed that the average values of TR, UIR, and IFR were 0.034%, 19.5%, and 0.51% respectively. The ranges of TR, UIR, and IFR for all states ranged from 0.007-0.157 (mean = 0.048), 7.31-185.6 (mean = 38.89), and 0.04-2.22% (mean = 0.22%). Among the time-varying TR equations, the power function showed better fitness, which indicated a decline in TR decreasing from 227.58 (T1) to 0.022 (T212). The general equation of tvSIRu showed that both the UIR and IFR were gradually increasing, wherein, the estimated value of UIR was 9.1 (95%CI 5.7-14.0) and IFR was 0.70% (95%CI 0.52-0.95%) at T212. INTERPRETATION: Despite the declining trend in TR and IFR, the UIR of COVID-19 in the United States is still on the rise, which, it was assumed would decrease with sufficient tests or improved countersues. The US medical system might be largely affected by severe cases amidst a rapid spread of COVID-19.

An enolase inhibitor for the targeted treatment of ENO1-deleted cancers.

Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We have previously identified a subset of cancers harbouring homozygous deletion of the glycolytic enzyme enolase (ENO1) that have exceptional sensitivity to inhibition of its redundant paralogue, ENO2, through a therapeutic strategy known as collateral lethality. Here, we show that a small-molecule enolase inhibitor, POMHEX, can selectively kill ENO1-deleted glioma cells at low-nanomolar concentrations and eradicate intracranial orthotopic ENO1-deleted tumours in mice at doses well-tolerated in non-human primates. Our data provide an in vivo proof of principle of the power of collateral lethality in precision oncology and demonstrate the utility of POMHEX for glycolysis inhibition with potential use across a range of therapeutic settings.

Antibody Detection and Dynamic Characteristics in Patients With Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, respectively, and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, respectively, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.

Maternal Health and Green Spaces in China: A Longitudinal Analysis of MMR Based on Spatial Panel Model.

The positive impact of green spaces on public health has attracted increasing attention, and maternal health has also been shown to be related to green spaces. However, there are different kinds of green space indicators that represent different mechanisms for mitigating maternal health, and few studies have investigated the different relevance amongst them with longitudinal data. This study explores the correlation between various green space indicators and maternal health using spatial panel models with provincial data from China from 2007 to 2016. The results indicate that all kinds of green spaces could decrease maternal mortality, wherein public green spaces may play a key role. In terms of spatial correlation, an increase in green space coverage in adjacent provinces may also result in a slight decline in maternal mortality. This paper provides valuable insight into the correlation between maternal health and green spaces.

Biodegradable bioadhesive nanoparticle incorporation of broad-spectrum organic sunscreen agents.

Conventional emulsion-based sunscreen formulations are limited by postapplication epicutaneous penetration that increases the risk of allergic dermatitis, cellular damage, and filter photodegradation upon ultraviolet radiation (UVR) exposure. Encapsulation of the UVB filter padimate O within bioadhesive biodegradable nanoparticles (BNPs) composed of poly(d,l-lactic acid)-hyperbranched polyglycerol was previously shown to enhance UVR protection while preventing skin absorption. Herein, we assess the capacity of BNP co-incorporation of avobenzone and octocrylene to provide broad-spectrum UVR protection. The ratio of UV filters within nanoparticles (NPs) was optimized for filter-filter stabilization upon UV irradiation and maximum drug loading. In vitro water-resistance test showed significant particle retention at 85% over 3 hr. In a pilot clinical study, protection against UVR-induced erythema of BNPs was found to be comparable to the FDA standard P2. Thus, sunscreen formulations utilizing BNP incorporation of a combination of organic filters may offer key safety and performance advantages.

Delimitating the Natural City with Points of Interests Based on Service Area and Maximum Entropy Method.

The natural city, which is essential to understand urban physical scale and identify urban sprawling in urban studies, represents the urban functional boundaries of the city defined by human activities rather than the administrative boundaries. Most studies tend to utilize physical environment data such as street networks and remote sensing data to delimitate the natural city, however, such data may not match the real distribution of human activity density in the new cities or even ghost cities in China. This paper suggests aggregating the natural city boundary from the service area polygons of points of interest based on Reilly's Law of Retail Gravitation and the maximum entropy method, since most points of interests provide services for surrounding communities, reflecting the vitality in a bottom-up way. The results indicate that the natural city defined by points of interests shows a high resolution and accuracy, providing a method to define the natural city with POIs.

Synthesis and Evaluation of Chloroquine-Containing DMAEMA Copolymers as Efficient Anti-miRNA Delivery Vectors with Improved Endosomal Escape and Antimigratory Activity in Cancer Cells.

Chloroquine-containing 2-(dimethylamino)ethyl methacrylate copolymers (PDCs) are synthesized by reversible addition-fragmentation chain-transfer polymerization. Systematic evaluation is performed to test the hypothesis that presence of chloroquine (CQ) in the PDC structure will improve miRNA delivery due to enhanced endosomal escape while simultaneously contribute to anticancer activity of PDC/miRNA polyplexes through inhibition of cancer cell migration. The results show that miRNA delivery efficiency is dependent both on the molecular weight and CQ. The best performing PDC/miRNA polyplexes show effective endosomal escape of miRNA. PDC polyplexes with therapeutic miR-210 show promising anticancer activity in human breast cancer cells. PDC/miRNA polyplexes show excellent ability to inhibit migration of cancer cells. Overall, this study supports the use of PDC as a promising polymeric drug platform for use in combination anti-metastatic and anticancer miRNA therapeutic strategies.

Tumor-Penetrating Nanoparticles for Enhanced Anticancer Activity of Combined Photodynamic and Hypoxia-Activated Therapy.

Poor tumor penetration is a major challenge for the use of nanoparticles in anticancer therapy. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in inadequate exposure to antitumor therapeutics and contributes to development of chemoresistance and increased metastasis. In the present study, we developed iRGD-modified nanoparticles for simultaneous tumor delivery of a photosensitizer indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine (TPZ). The iRGD-modified nanoparticles loaded with ICG and TPZ showed significantly improved penetration in both 3D tumor spheroids in vitro and orthotopic breast tumors in vivo. ICG-mediated photodynamic therapy upon irradiation with a near-IR laser induced hypoxia, which activated antitumor activity of the codelivered TPZ for synergistic cell-killing effect. In vivo studies demonstrated that the nanoparticles could efficiently deliver the drug combination in 4T1 orthotopic tumors. Primary tumor growth and metastasis were effectively inhibited by the iRGD-modified combination nanoparticles with minimal side effects. The results also showed the anticancer benefits of codelivering ICG and TPZ in a single nanoparticle formulation in contrast to a mixture of nanoparticles containing individual drugs. The study demonstrates the benefits of combining tumor-penetrating nanoparticles with hypoxia-activated drug treatment and establishes a delivery platform for PDT and hypoxia-activated chemotherapy.

Dual-Function Polymeric HPMA Prodrugs for the Delivery of miRNA.

An HPMA-based polymeric prodrug of a CXCR4 antagonist, AMD3465 (P-SS-AMD), was developed as a dual-function carrier of therapeutic miRNA. P-SS-AMD was synthesized by a copolymerization of HPMA with a methacrylamide monomer in which the AMD3465 was attached via a self-immolative disulfide linker. P-SS-AMD showed effective release of the parent AMD3465 drug following treatment with intracellular levels of glutathione (GSH). The AMD3465 was released in the cells and exhibited functional CXCR4 antagonism, demonstrated by inhibition of the CXCR4-mediated cancer cell invasion. Due to its cationic character, P-SS-AMD could form polyplexes with miRNA and mediate efficient transfection of miR-200c mimics to downregulate expression of a downstream target ZEB-1 in cancer cells. The combined P-SS-AMD/miR-200c polyplexes showed improved ability to inhibit cancer cell migration when compared with individual treatments. The reported findings validate P-SS-AMD as a dual-function delivery vector that can simultaneously deliver a therapeutic miRNA and function as a polymeric prodrug of CXCR4 antagonist.

Chloroquine-Containing HPMA Copolymers as Polymeric Inhibitors of Cancer Cell Migration Mediated by the CXCR4/SDF-1 Chemokine Axis.

Chloroquine-containing HPMA copolymers (pCQs) were synthesized for the first time by copolymerization of methacryloylated hydroxychloroquine and HPMA. The copolymers showed lower cytotoxicity when compared with hydroxychloroquine. Treatment of cancer cells with pCQ resulted in decreased surface expression of chemokine receptor CXCR4. The pCQ copolymers showed effective inhibition of CXCR4/SDF1-mediated cancer cell migration that was fully comparable with a commercial small-molecule CXCR4 antagonist AMD3100. The reported pCQ represent unique and simple polymeric drugs with potential use as part of a combination antimetastatic therapies.

SF2312 is a natural phosphonate inhibitor of enolase.

Despite being crucial for energy generation in most forms of life, few if any microbial antibiotics specifically inhibit glycolysis. To develop a specific inhibitor of the glycolytic enzyme enolase 2 (ENO2) for the treatment of cancers with deletion of ENO1 (encoding enolase 1), we modeled the synthetic tool compound inhibitor phosphonoacetohydroxamate (PhAH) into the active site of human ENO2. A ring-stabilized analog of PhAH, in which the hydroxamic nitrogen is linked to Cα by an ethylene bridge, was predicted to increase binding affinity by stabilizing the inhibitor in a bound conformation. Unexpectedly, a structure-based search revealed that our hypothesized backbone-stabilized PhAH bears strong similarity to SF2312, a phosphonate antibiotic of unknown mode of action produced by the actinomycete Micromonospora, which is active under anaerobic conditions. Here, we present multiple lines of evidence, including a novel X-ray structure, that SF2312 is a highly potent, low-nanomolar inhibitor of enolase.