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The selective anti-tumor activity and less toxic nature of hypoxia-activated prodrugs including tirapazamine (TPZ) are harbored by hypoxia levels in tumors, the inadequacy of which leads to failure in clinical trials.

Active transcytosis has recently sparked great interest in drug delivery as a novel route for tumor extravasation and infiltration. However, the rational design of transcytosis-inducing nanomedicines remains challenging. We recently demonstrated that the γ-glutamyl transpeptidase (GGT)-responsive polymer cationization induced efficient adsorption-mediated transcytosis (AMT). However, it remains unclear how the nanomedicines' physicochemical properties influence the GGT-responsive cationization and induced transcytosis behaviors. Herein, through a combination of experimental techniques and molecular dynamics (MD) simulations, we find that the random copolymers with high hydrophobic monomers tend to form compact structures accessible to the catalytic site of GGT, leading to a fast cationization and thus high transcytosis efficiency, while the homopolymers of the hydrophilic GGT-sensitive monomers have elongated structures unable to enter the active site and thus exhibit poor GGT sensitivity. As a result, the more hydrophobic polymer-drug conjugates with high camptothecin contents exhibit higher GGT-responsive activity, which in turn leads to faster cationization and cellular internalization, enhanced tumor infiltration, and more potent antitumor activity. These findings indicate the hydrophobicity is a main parameter determining the GGT catalytic activity and transcytosis efficiency of the GGT-activatable co(homo)polymers, providing guidelines for the rational design of GGT-induced charge reversal carriers for transcytotic nanomedicines.

Urban cooling becomes a priority in urban planning and design practices. Limited by the slow running speed and prescriptive nature, existing computational tools such as simulation and optimization are yet to be fully integrated in the design decision-making process. This paper describes the Machine Learning-Enhanced Design Optimizer (MLEDO), a novel workflow in search of optimal design option for urban cooling. A physics-based simulation model was developed to assess the cooling performances of a large database of urban design variations. The database was used to train an Artificial Neural Network model, which was then linked with a Genetic Algorithm to rapidly identify optimal design options. The MLEDO workflow was evaluated using a new development urban site against a traditional Simulation-based Genetic Algorithm Design Optimizer (SGADO) as well as human designers. MLEDO outperformed the latter two in terms of efficiency and the performance of the optimal design options. It can also quantify the importance of design parameters in their contribution to cooling performances, which can be used to enhance the understanding of human designers and inform design revisions. MLEDO has the potential to be further developed into a software tool in support of early-stage urban design.

Subcutaneous injection of insulin is the current standard medication for many diabetic patients. Convenient and painless noninvasive transdermal insulin delivery has long been pursued but yet succeeded due to no such technologies for large biomacromolecules. We find a tertiary amine oxide-based polyzwitterion, OPDMA, that can efficiently penetrate both the stratum corneum (SC) and viable epidermis into circulation. So its conjugate with insulin, OPDMA-I, applied on the skin can exhibit hypoglycemic effects as efficiently as subcutaneously injected insulin in type-1 diabetic mice and minipigs. The unique pH-dependent cationic-to-zwitterionic transition of OPDMA in the characteristic acidic-to-neutral pH gradient from the skin surface to deep SC enables fast transdermal delivery of OPDMA and its conjugate. On the skin, OPDMA binds to carboxylic acids in the acidic sebum layer, enriching OPDMA-I on the SC. As pH increases in deeper SC layers, binding between OPDMA-I and the skin weakens gradually, allowing for diffusion through inter-corneocyte gaps and penetration into viable epidermis and finally entering the systemic circulation via dermal lymphatic vessels. This process does not alter SC microstructures or cause any physiological changes in the skin. This study represents a groundbreaking example of noninvasive transdermal protein delivery.

Jane Jacobs (1961) theorized that four urban form conditions, namely, mixed use, short block, aged buildings and density, are indispensable for the ‘exuberant diversity’ and conducive to, or perhaps even determinant of, the success of a city district. Jacobs’ theory has been used widely as a reference point in case study research and policy and design prescriptions. We found five studies that attempted to test it more formally, using various performance indicators such as mobile phone activities, walking, crime and mortality. Their findings were inconsistent and unable to settle theoretical controversies. Questions remained as what performance indicators are most strongly associated with her urban form conditions? Are these conditions independently associated with desired outcomes or in combination and what are the interaction effects? Our study aimed to test Jacobs’ theory that urban form conditions contribute to the vitality and success of city districts. Jacobs’ urban form conditions were measured using GIS data for each of Hong Kong’s Tertiary Planning Unit. Performance outcomes were gauged using a combination of ‘new urban data’, comprising Twitter activities, sentiment tones and Point-Of-Interest (POI), and ‘traditional data’, comprising walking commute, employment and mortality. Urban context, income and demographic indicators were used as controls in fitting spatial regression models to predict measures of performances based on urban conditions. Results showed that Jacobs’ urban form conditions contribute positively to ‘vitality’ indicators such as the density of tweets, walking trips and POI, but not with ‘failure and success’ indicators such as expressed sentiment on Twitter, employment, or mortality. Out findings suggest that her theory largely hold for Hong Kong, except that dwelling density should be substituted by building density, whilst tall buildings associated positively with desirable outcomes, contrary to Jacobs’ observation in the American context. More generally, we demonstrate how new urban data can be used to evaluate classic planning theories at scale.

Urban rail development can increase land value, reduce commute time, and increase accessibility, as reported in the literature. However, little is known about the impact of opening urban rail transit stations on people's sentiment, particularly in the context of large metropolises where population density is significantly high. This paper investigates such impact by studying six new transit stations opened in Hong Kong. People's sentiment and activity in station nearby areas are estimated by tweet sentiment and tweet activity. We use the difference-in-difference model to study the impact of opening new transit stations. Tweet sentiment, tweet activity, tweet content, and footprints of people who visit the station-influenced area ‘before and after’ the opening of transit stations are analyzed. The results suggest that, in general, the introduction of transit stations causes a positive change in tweet activity, and the change is statistically significant after six months. Regarding tweet sentiment, new transit stations tend to pose a mixed effect in a short-term, a positive influence on areas with high-density residential places, yet a negative influence on areas with a large proportion of nature reserve areas. These short-term effects, positive or negative, become not significant in the long term (after twelve months). Our analysis also confirmed that the introduction of new transit stations increased accessibility from (to) other parts of the city to(from) the station's nearby area, which was shown by the expanded locations sustaining users visited. These findings indicate that the urban rail transit system in Hong Kong promotes more active neighborhoods yet does not always promotes positive influence on people's sentiment. Further studies are needed to make future urban rail transit systems promoting active and happy neighborhoods. The study is relevant to the Belt and Road Initiative (BRI) in methodologies, data, and findings. The social media analysis method used in this study, including text mining and sentiment analysis, can be easily extended to multiple language analysis for Singapore, Malaysia, as well as other regions in the belt and road plan. The developed tools could contribute to analyzing the influence of cross-country projects on local neighborhoods in the belt and road plan.

Lipopolyplexes have received extensive attention lately in gene therapy delivery. However, the interactions between the polyplex and the liposome and their underlying molecular mechanisms remain to be elucidated. Here, we adopted a simple model, mainly to illustrate the impact of polyplex charge density on the self-assembly of liposomes (containing DOPE and CHEMS lipids) using coarse-grained molecular dynamics simulations. Our simulation results show that when the charge density increases in the polyplex, more lipids, especially CHEMS (a negatively charged helper lipid) lipids, are attracted to the polyplex (positively charged) surface, and meanwhile nearby water molecules are driven away from the polyplex, resulting in a less spherical liposome. Energy decomposition analyses further reveal that, at higher charge densities, the polyplex exhibits much stronger interactions with CHEMS lipids than with water molecules, with the majority contribution from electrostatic interactions. In addition, the mobility of lipids, especially CHEMS, is reduced as the polyplex charge density increases, indicating a more rigid liposome. Overall, our molecular dynamics simulations elucidate the influence of polyplex charge density on the liposome self-assembly process at the atomic level, which provides a complementary approach to experiments for a better understanding of this promising gene therapy delivery system.

Background Cowpea (Vigna unguiculata L. Walp.) is an economically important crop. It is nutritious and popular with consumers. However, it has been listed as one of the agricultural products of critical concern about safety in China and cyromazine is the major risk factor. Objectives This study analyzed the dissipation and permeation kinetics of cyromazine residue in cowpea, to offer a scientific basis for the rational use of pesticide and ensure the safety of agricultural products. Materials and methods The dissipation and residue level of the systemic insecticide cyromazine on cowpea under field and stored conditions were investigated. Subsequently, the spatial distribution of cyromazine was studied using mass spectrometry imaging to visualize the dynamic processes of permeation and migration in the tissues post pesticide application. Results The dissipation processing of cyromazine in cowpea was shown to follow the first-order kinetics and half-life was 7.76 d in the field. In cowpea, the permeation and migration rate of cyromazine was faster than that in kidney beans and accumulation was mainly in the pulp. It is not safe to apply cyromazine to cowpeas with reference to the application method on kidney beans. Conclusions These findings present vital data for the determination of risks linked with cowpea consumption and pesticide intake.

The selective anti-tumor activity and less toxic nature of hypoxia-activated prodrugs including tirapazamine (TPZ) are harbored by hypoxia levels in tumors, the inadequacy of which leads to failure in clinical trials. Thus, the development of effective clinical applications of TPZ requires advanced strategies to intensify hypoxia levels in tumors effectively and safely. In this study, we designed and fabricated a paclitaxel (PTX)-loaded dual-response delivery system with a low dose (

Trees provide cooling benefits through shading and evapotranspiration; they are regarded as an important measure in heat-resilient urban planning and policies. Knowing where to plant trees for maximum cooling benefits, given practical and resource constraints, remains a challenge in both practice and research. Literature in the field of tree modelling and location optimization is limited, either by the incompleteness in accounting for tree shading, evapotranspiration, and the modifying effect of wind, or by the slow-running speed of the Computational Fluid Dynamics model, making them less applicable in practice. This paper describes a novel method to search for the optimal locations for trees to maximize their cooling benefits in an urban environment. A non-CFD simulation model was applied to assess on-site heat stress under the influences of trees, which was evaluated using field measurements conducted under hot, temperate, and cool weather conditions in an urban park in Hong Kong. It was then linked to a genetic algorithm in search of a near-optimal tree layout. The proposed method was tested in the same park, and it can automatically identify locations to plant new trees to minimize heat stress, subject to practical constraints such as avoiding existing buildings and utilities. It can also identify the optimal layout to rearrange the existing 55 trees, hypothetically, which is expected to cool the park (around 30,000 m2) by up to 0.3 ℃ in the site average UTCI equivalent temperature compared with the worse scenario. Trees can cool the most if they are concentrated on the leeward side of the park relative to the prevailing wind, rather than spread evenly. The new method runs significantly faster than existing approaches, and it can inform research and landscape design practices concerning park cooling as a goal.

A green building is believed to promote green behaviors from energy-saving to waste recycling. Green building certifications have attracted wide interest, and some were made mandatory for publicly funded developments in cities such as Hong Kong. Policymakers debate whether the city’s expanding public housing stock should be exempted from the green certification mandate for reasons of cost, while evidence of behavioral benefits in green residential buildings is thin, or non-existent for public housing estates. This paper describes a post-occupancy evaluation study on self-reported green behaviors in Hong Kong’s public housing estates. The study subjects are 400 occupants from two pairs of public rental housing estates with or without green certifications. A natural experiment was conducted, in which surveyed occupants were allocated to certified and uncertified estates via a random lottery, without significant differences in socioeconomic characteristics and propensity to green behaviors a priori. The results show that green-certified housing estates partially induced energy-saving behaviors, but not water saving or waste recycling, nor does it enhance satisfaction or green awareness. A certification alone is insufficient to induce behavioral changes, rather, efforts should be invested in conveying the green message, public education, and appropriate fiscal incentives.

Kidney transplant recipients with cancer are at higher risk of kidney transplant rejection (KTR), and the safety of immune checkpoint inhibitors (ICIs) is unclear. The present study investigates the relationship between ICIs and KTR using data from the Food and Drug Administration Adverse Event Reporting System (FAERS).Case reports of KTR inducted by ICIs in FAERS from 1 January 2011, to 30 June 2021, were collected, and a disproportionate analysis was performed to assess the correlation between ICIs and KTR.A total of 99 cases of ICI-related KTR were reported in the FAERS database. Most of them were male patients (n = 63, 84.0%), and more than half of patients suffered from malignant melanoma (n = 46, 52.9%). The median onset time after the medication was 22 days, the withdrawal rates of ICIs were 78.0%, and the overall death rate was 29.3%. In general, there was a significant relevance between ICIs and KTR (ROR = 3.92[3.21-4.79] IC025 = 1.56), of which PD-1 was the most prominent (n = 81 ROR = 5.26[4.22-6.57] IC025 = 1.86).ICIs may increase the risk of KTR in organ transplant recipients with cancer.

The Delta variant of SARS-CoV-2 has inflicted heavy burdens on healthcare systems globally, although direct evidence on the quantity of exhaled viral shedding from Delta cases is lacking. Literature remains inconclusive on whether existing public health guidance, formulated based on earlier evidence of COVID-19, should respond differently to more infectious viral strains. This paper describes a study on an outbreak of the Delta variant of COVID-19 in an auditorium, where one person contracted the virus from three asymptomatic index cases sitting in a different row. Field inspections were conducted on the configuration of seating, building and ventilation systems. Numerical simulation was conducted to retrospectively assess the exhaled viral emission, decay, airborne dispersion, with a modified Wells-Riley equation used to calculate the inhalation exposure and disease infection risks at the seat level. Results support the airborne disease transmission. The viral emission rate for Delta cases was estimated at 31 quanta per hour, 30 times higher than those of the original variant. The high quantity of viral plume exhaled by delta cases can create a risky zone nearby, which, for a mixing ventilation system, cannot be easily mitigated by raising mixing rates or introducing fresh air supply. Such risks can be reduced by wearing an N95 respirator, less so for social distancing. A displacement ventilation system, through which the air is supplied at the floor and returned from the ceiling, can reduce risks compared with a mixing system. The study has implications for ventilation guidelines and hygiene practices in light of more infectious viral strains of COVID-19.

Urban heat disrupts the use of parks, although the extent of such disruptions remains disputed. Literature relies on “small data” methods, i.e., questionnaires, field observations, or human-subject experiments, to capture the behavioural response to heat. Their findings are often in contradiction with each other, possibly due to the small sample sizes, the short study period, or the few sites available in a single study. The rise of “big data” such as social media offers new opportunities, yet its reliability and usefulness remain unknown. This paper describes the first study using Twitter data (tweets) to study park attendance under the influence of hot weather. Some 700,000 tweets with GPS coordinates inside major parks were obtained in Hong Kong over a period of three years. Field measurements were conducted in parallel in a large park covering the hot and cool seasons. Both the “small” and “big data” were analyzed and compared to each other. Findings suggest that a 1 ℃ increase in temperature was associated with some 4% drop in park attendance and some 1% drop in park tweets. The differences between the two data sources be explained by the ‘leakage’ of indoor tweets to parks caused by GPS drift near buildings. The Universal Thermal Climate Index can better predict self-reported thermal sensations, compared with other biometeorological indicators. This study has contributed to methodologies and new evidence to the study of behaviors and thermal adaptations in an outdoor space, and geo-coded tweets can serve as a powerful data source.

High-fidelity DNA sequencing using solid-state nanopores remains a big challenge, partly due to difficulties related to efficient molecular capture and subsequent control of the dwell time. To help address these issues, here we propose a sequencing platform consisting of stacked two-dimensional materials with tailored structures containing a funnel-shaped step defect and a nanopore drilled inside the nanochannel. Our all-atom molecular dynamics (MD) simulations showed that, assisted by the step defect, single-stranded DNA (ssDNA) can be transported to the nanopore in a deterministic way by pulsed transversal electric fields. Furthermore, different types of DNA bases can reside in the pore for a sufficiently long time which can be successfully differentiated by longitudinal ionic currents. By using the decoupled driving forces for ssDNA transport and ionic current measurements, this approach holds potential for high-fidelity DNA sequencing.

In this study, we established a feasible strategy to construct a new type of metallo-polymer with helicoidal structure through the combination of covalent polymerization and intramolecular coordination-driven self-assembly. In the design, a tetratopic monomer (M) was prepared with two terminal alkynes in the outer rim for polymerization, and two terpyridines (TPYs) in the inner rim for subsequent folding by selective intramolecular coordination. Then, the linear covalent polymer (P) was synthesized by polymerization of M via Glaser-Hay homocoupling reaction. Finally, intramolecular coordination interactions between TPYs and Zn(II) folded the backbone of P into a right- or left-handed metallo-helicoid (H) with double rims. Owing to multiple positive charges on the inner rim of helicoid, double-stranded DNA molecules (dsDNA) could interact with H through electrostatic interactions. Remarkably, dsDNA allowed exclusive formation of H with right handedness by means of chiral induction.

Aims We estimated the association between outdoor light at night at the residence and risk of coronary heart disease (CHD) within a prospective cohort of older adults in Hong Kong. Methods and results Over a median of 11 years of follow-up, we identified 3772 incident CHD hospitalizations and 1695 CHD deaths. Annual levels of outdoor light at night at participants’ residential addresses were estimated using time-varying satellite data for a composite of persistent night-time illumination at ∼1 km2 scale. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between outdoor light at night at the residence and risk of CHD. The association between light at night and incident CHD hospitalization and mortality exhibited a monotonic exposure-response function. An interquartile range (IQR) (60.0 nW/cm2/sr) increase in outdoor light at night was associated with an HR of 1.11 (95% CI: 1.03, 1.18) for CHD hospitalizations and 1.10 (95% CI: 1.00, 1.22) for CHD deaths after adjusting for both individual and area-level risk factors. The association did not vary across strata of hypothesized risk factors. Conclusion Among older adults, outdoor light at night at the residence was associated with a higher risk of CHD hospitalizations and deaths. We caution against causal interpretation of these novel findings. Future studies with more detailed information on exposure, individual adaptive behaviours, and potential mediators are warranted to further examine the relationship between light at night and CHD risk.

Open spaces in Hong Kong are in short supply and they are often underused due to the adverse climate, especially in hot and humid summer. This is a missed opportunity that can be otherwise realized to promote health and social interactions for local communities. The high density urban environment makes the condition worse by raising the urban heat island effect and leaving planners with fewer mitigation options. This study aims to test the hypotheses that an unfavourable thermal environment disrupts the use of outdoor open spaces; if yes, whether such disruptions differ by age groups. On-site measurement and computer simulations were conducted in three open spaces in public housing estates in Ngau Tau Kok, Hong Kong. Thermal conditions were assessed using the Universal Thermal Climate Index. Occupant activities were recorded, together with a questionnaire survey. Results showed that an open space purposefully designed for breeze and shading was 2.0°C cooler in Universal Thermal Climate Index compared with the other two. It attracted more optional/social activities, higher frequency of visits, and longer duration of stay. The elderly activities were more susceptible to disruptions from heat stress compared with younger groups. Elderly activities largely diminish when ambient thermal environment exceed 39°C in Universal Thermal Climate Index. Findings have implications to design and retrofitting of open spaces in order to maximize their use.

Poor housing conditions are known to be associated with infectious diseases such as high Coronavirus disease 2019 (COVID-19) incidences. Transmission causes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in poor housing conditions can be complex. An understanding of the exact mechanism of transmission can help to pinpoint contributing environmental issues. Here, we investigated a Hong Kong COVID-19 outbreak in early 2021 in four traditional Tong Lau houses with subdivided units. There are more than 80 subdivided units of less than 20 m2floor area each on average. With a total of 34 confirmed COVID-19 cases, the outbreak had an attack rate of 25.4%, being one of the highest attack rates observed in Hong Kong, and ranked among the highest attack rates in reported outbreaks internationally. Tracer gas leakage and decay measurements were performed in the drainage system and in the subdivided units to determine the transport of infectious aerosols by the owner-modified sophisticated wastewater drainage pipe networks and the poor ventilation conditions in some subdivided units. The results show that the outbreak was probably due to multiple transmission routes, i.e. by the drainage pipe spread of stack aerosols, which is enhanced by poor ventilation in the subdivided units.

Traffic congestion and accidents take a toll on commuters' daily experiences and society. Locating the venues prone to congestion and accidents and capturing their perception by public members is invaluable for transport policy-makers. However, few previous methods consider user perception toward the accidents and congestion in finding and profiling the accident- and congestion-prone areas, leaving decision-makers unaware of the subsequent behavior responses and priorities of retrofitting measures. This study develops a framework to identify and characterize the accident- and congestion-prone areas heatedly discussed on social media. First, we use natural language processing and deep learning to detect the accident- and congestion-relevant Chinese microblogs posted on Sina Weibo, a Chinese social media platform. Then a modified Kernel Density Estimation method considering the sentiment of microblogs is employed to find the accident- and congestion-prone regions. The results show that the 'congestion-prone areas' discussed on social media are mainly distributed throughout the historical urban core and the Northwest of Pudong New Area, in reasonably good agreements with actual congestion records. In contrast, the 'accident-prone areas' are primarily found in locations with severe accidents. Finally, the above venues are characterized in spatio-temporal and semantic aspects to understand the nature of the incidents and assess the priority level for mitigation measures. The outcomes can provide a reference for traffic authorities to inform resource allocation and prioritize mitigation measures in future traffic management.