A 14-amino acid cationic peptide Bolespleenin334-347 from the marine fish mudskipper Boleophthalmus pectinirostris exhibiting potent antimicrobial activity and therapeutic potential.

Antimicrobial peptides (AMPs) are an important component of innate immunity in both vertebrates and invertebrates, and some of the unique characteristics of AMPs are usually associated with their living environment. The marine fish, mudskipper Boleophthalmus pectinirostris, usually live amphibiously in intertidal environments that are quite different from other fish species, which would be an exceptional source of new AMPs. In the study, an AMP named Bolespleenin334-347 was identified, which was a truncated peptide derived from a new functional gene found in B. pectinirostris, that was up-regulated in response to bacterial challenge. Bolespleenin334-347 had only 14 amino acid residues, including five consecutive arginine residues. It was found that the peptide had broad-spectrum antibacterial activity, good thermal stability and sodium ion tolerance. Bolespleenin334-347 killed Acinetobacter baumannii and Staphylococcus aureus by disrupting the structural integrity of the bacterial membrane, leading to leakage of the cellular contents, and inducing accumulation of bacterial endogenous reactive oxygen species (ROS). In addition, Bolespleenin334-347 effectively inhibited biofilm formation of A. baumannii and S. aureus and long-term treatment did not lead to the development of resistance. Importantly, Bolespleenin334-347 maintained stable activity against clinically multi-drug resistant bacterial strains. In addition, it was noteworthy that Bolespleenin334-347 showed superior efficacy to LL-37 and vancomycin in a constructed mouse model of MRSA-induced superficial skin infections, as evidenced by a significant reduction in bacterial load and more favorable wound healing. This study provides an effective antimicrobial agent for topical skin infections with potential therapeutic efficacy for infections with drug-resistant bacteria, including MRSA.

How digital inclusive finance promotes social entrepreneurship: Evidence from 282 cities in China.

Social entrepreneurship (SE) plays a positive role in addressing a range of social issues, and thus it is essential to study how to promote SE. Using panel data from 282 Chinese cities from 2011 to 2021, this study explores the mechanism through which digital inclusive finance affects SE. The results indicate that digital inclusive finance has a positive impact on SE, which still holds after considering endogeneity and undergoing a series of robustness tests. In addition, mechanism analysis shows that digital inclusive finance affects SE by alleviating financing constraints and promoting common prosperity. Furthermore, the effect of digital inclusive finance is stronger in cities with a strong Buddhist culture and more judicially civilized. Policy recommendations are also proposed.

Complete genome sequence of a novel Prescottella sp. R16 isolate from deep-sea sediments in the western Pacific.

Prescottella, a distinct genus separate from Rhodococcus, has garnered attention for its adaptability and ecological versatility. In this study, a Gram-stain positive and ovoid-rod shaped the actinobacterium strain R16 was isolated from deep-sea sediment (with a depth of 6,310 m) in the Western Pacific. On the basis of 16S rRNA gene sequence analysis, average nucleotide identity and phylogenomic analysis, strain R16 clearly represents a novel species within the genus Prescottella. Genomic analyses indicate Prescottella sp. R16 contains a circular chromosome of 4,531,251 bp with an average GC content of 68.9%, 4,208 protein-coding genes, 51 tRNA genes, and 12 rRNA operons. Additionally, four CRISPRs and 24 genomic islands are also identified. The presence of rich categories related to catalytic activity, membrane part and metabolic process highlights their involvement in cellular component, biological process, and molecular function. The genome sequence of strain R16 also revealed the presence of 13 putative biosynthetic gene clusters for secondary metabolites, including those for ε-Poly-L-lysine, ectoine, heterobactin, isorenieratene and corynecin, suggesting its potential for antibiotic production and warranting further exploration.

A novel antimicrobial peptide Scyreptin1-30 from Scylla paramamosain exhibiting potential therapy of Pseudomonas aeruginosa early infection in a mouse burn wound model.

Antimicrobial resistance (AMR) constitutes a significant global threat to human health. In recent years, there has been a concerning surge in infections caused by multidrug-resistant bacteria, highlighting the pressing need to urgently explore novel and effective alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) have emerged as a focal point of research, capturing significant attention as promising antimicrobial agents. In this study, we have identified a novel cationic antimicrobial peptide (AMP) named Scyreptin1-30, derived from the marine invertebrate Scylla paramamosain. The results showed that Scyreptin1-30 exhibits a broad-spectrum antimicrobial activity, demonstrating significant potency against both bacteria and fungi, and even against the clinically isolated multidrug-resistant bacteria Pseudomonas aeruginosa. Moreover, Scyreptin1-30 exhibited rapid bactericidal kinetic. The results of antibacterial mechanism showed that Scyreptin1-30 destroyed the integrity of bacterial membranes, leading to bacterial death and exhibited potent anti-biofilm activity against P. aeruginosa. The activity of Scyreptin1-30 against bacteria had a favorable thermal stability, displayed a certain ion tolerance, and showed no discernible cytotoxicity when assessed against both the mammalian cell line HEK293T and the fish cell lines ZF4. In an In vivo study, Scyreptin1-30 exhibited a remarkably reduction in the bacterial load caused by multidrug-resistant P. aeruginosa at the site of infection, and promoted wound healing in a mouse model of burn infection. This study indicated that Scyreptin1-30 holds promise as an effective antibacterial agent, potentially serving as a topical skin treatment against multidrug-resistant bacterial infections, including those caused by P. aeruginosa.

Projections of mortality risk attributable to short-term exposure to landscape fire smoke in China, 2021-2100: a health impact assessment study.

BACKGROUND: Landscape fire smoke, including smoke from all vegetation burning in natural and cultural landscapes, remains a threat to the health of the population. However, the future health impacts of landscape fire smoke in China have not been sufficiently investigated. We aimed to estimate the mortality risk attributable to landscape fire-related PM2·5 under different scenarios. METHODS: In this health impact assessment study, we used the projected population and landscape fire-related PM2·5 concentration to calculate deaths attributable to short-term exposure to landscape fire smoke PM2·5 during 2021-2100. We did the analysis in three defined future periods: 2021-40 (near term), 2051-70 (medium term), and 2081-2100 (long term), with 1986-2005 as the historical period. We used fire-specific short-term epidemiological functions with the regional parameters specific to China. We assessed the mortality risks of landscape fire-related smoke and further identified their spatiotemporal distribution under two shared socioeconomic pathway (SSP) scenarios: SSP1-2·6, an optimistic scenario with strict control of carbon emissions, and SSP2-4·5, an intermediate scenario with weaker control of carbon emissions. FINDINGS: The national mortality rate attributable to short-term exposure (ie, a few days) to landscape fire-related PM2·5 is projected to increase compared with historical values. The national deaths attributable to landscape fire smoke PM2·5 could peak in 2021-40, with increases of 28·10% (95% CI 14·08-53·11) under the SSP1-2·6 scenario and 37·38% (14·08-53·11) under the SSP2-4·5 scenario. Deaths would then decrease slightly during 2051-70 and 2081-2100. The provinces with the highest projected number of deaths attributable to landscape fire-related PM2·5 are located in east and south-central China, and those with the largest percentage increase in projected deaths are located in northwest and southwest China. INTERPRETATION: Our results suggest that global warming could increase the contribution of landscape fire smoke to the total PM2·5 concentration, leading to an increase in the mortality rate in China. Our findings could help policy makers implement effective interventions in hotspot areas during different periods to reduce the impact of landscape fire smoke on human health. FUNDING: The National Natural Science Foundation of China, National Key Research and Development Program of China, and the Wellcome Trust.

Global age-structured spatial modeling for emerging infectious diseases like COVID-19.

Modeling the global dynamics of emerging infectious diseases (EIDs) like COVID-19 can provide important guidance in the preparation and mitigation of pandemic threats. While age-structured transmission models are widely used to simulate the evolution of EIDs, most of these studies focus on the analysis of specific countries and fail to characterize the spatial spread of EIDs across the world. Here, we developed a global pandemic simulator that integrates age-structured disease transmission models across 3,157 cities and explored its usage under several scenarios. We found that without mitigations, EIDs like COVID-19 are highly likely to cause profound global impacts. For pandemics seeded in most cities, the impacts are equally severe by the end of the first year. The result highlights the urgent need for strengthening global infectious disease monitoring capacity to provide early warnings of future outbreaks. Additionally, we found that the global mitigation efforts could be easily hampered if developed countries or countries near the seed origin take no control. The result indicates that successful pandemic mitigations require collective efforts across countries. The role of developed countries is vitally important as their passive responses may significantly impact other countries.

How to avoid a local epidemic becoming a global pandemic.

Here, we combine international air travel passenger data with a standard epidemiological model of the initial 3 mo of the COVID-19 pandemic (January through March 2020; toward the end of which the entire world locked down). Using the information available during this initial phase of the pandemic, our model accurately describes the main features of the actual global development of the pandemic demonstrated by the high degree of coherence between the model and global data. The validated model allows for an exploration of alternative policy efficacies (reducing air travel and/or introducing different degrees of compulsory immigration quarantine upon arrival to a country) in delaying the global spread of SARS-CoV-2 and thus is suggestive of similar efficacy in anticipating the spread of future global disease outbreaks. We show that a lesson from the recent pandemic is that reducing air travel globally is more effective in reducing the global spread than adopting immigration quarantine. Reducing air travel out of a source country has the most important effect regarding the spreading of the disease to the rest of the world. Based upon our results, we propose a digital twin as a further developed tool to inform future pandemic decision-making to inform measures intended to control the spread of disease agents of potential future pandemics. We discuss the design criteria for such a digital twin model as well as the feasibility of obtaining access to the necessary online data on international air travel.

Image-guided interstitial brachytherapy for recurrent cervical cancer after radiotherapy: A single institution experience.

Purpose: The aim of this study is to evaluate the efficacy and toxicity of image-guided high-dose rate (HDR) interstitial brachytherapy (ISBT) for the reirradiation of cervical cancer within a previously irradiated area. Methods and materials: Twenty-three consecutive patients with cervical cancer were reirradiated with curative intent using brachytherapy (BT) with or without external beam irradiation. The median biologically equivalent dose in 2-Gy fractions (EQD2) for reirradiation was 64.0 Gy (range: 31.3-95.1 Gy), and the median cumulative EQD2 (for primary treatment and reirradiation) was 152.4 Gy (range: 97.8-200.9 Gy). The average clinical target volume was 82.9 cm3 (range: 26.9-208.3 cm3), and the median treatment-free interval (TFI) was 13 months (range: 3-93 months). Results: The median follow-up time was 19 months (range: 2-59 months). The complete response rate after reirradiation was 56.5%. The 1-, 2- 3-, and 4-year post-relapse survival (PRS) rates were 65.2%, 43.5%, 33.8%, and 27.1%, respectively. The median reirradiation EQD2 D2cc of rectum and bladder was 39.5 Gy (range = 14.6-96.2 Gy) and 52.1 Gy (range = 29.1-114.2 Gy). The median cumulative EQD2 D2cc of rectum and bladder was 115.0 Gy (range = 84.4-189.3 Gy) and 130.5 Gy (range = 95.5-173.5 Gy). During follow-up, nine (39.1%) patients had experienced grade 3 or 4 late toxicities. Grade ≥3 rectal toxicity occurred in three patients (13.0%). Grade ≥3 urinary toxicity occurred in five patients (21.7%). One patient (4.3%) had both grade ≥3 urinary and rectal toxicity. Tumor volume, TFI, tumor invasion organ number, and local control were significant prognostic factors adversely affecting OS. Conclusions: For recurrent cervical cancer after radiotherapy, reirradiation of HDR-ISBT is feasible, even if the local tumor invasion is large, with a good chance of survival and acceptable side effects.

Healthy cities initiative in China: Progress, challenges, and the way forward.

China implemented the first phase of its National Healthy Cities pilot program from 2016-20. Along with related urban health governmental initiatives, the program has helped put health on the agenda of local governments while raising public awareness. Healthy City actions taken at the municipal scale also prepared cities to deal with the COVID-19 pandemic. However, after intermittent trials spanning the past two decades, the Healthy Cities initiative in China has reached a crucial juncture. It risks becoming inconsequential given its overlap with other health promotion efforts, changing public health priorities in response to the pandemic, and the partial adoption of the Healthy Cities approach advanced by the World Health Organization (WHO). We recommend aligning the Healthy Cities initiative in China with strategic national and global level agendas such as Healthy China 2030 and the Sustainable Development Goals (SDGs) by providing an integrative governance framework to facilitate a coherent intersectoral program to systemically improve population health. Achieving this alignment will require leveraging the full spectrum of best practices in Healthy Cities actions and expanding assessment efforts. Funding: Tsinghua-Toyota Joint Research Fund "Healthy city systems for smart cities" program.

Vulnerability and Resilience of Urban Traffic to Precipitation in China.

The concept of Healthy Cities, introduced by the World Health Organization, demonstrates the value of health for the whole urban system. As one of the most important components of urban systems, transportation plays an important role in Healthy Cities. Many transportation evaluation systems focus on factors such as road networks, parking spaces, transportation speed, accessibility, convenience, and commuting time, while the vulnerability and resilience of urban transportation are rarely evaluated. This study presents the preliminary progress in the evaluation of traffic vulnerability and resilience during precipitation events in 39 Chinese cities. Traffic congestion index data, derived from the Baidu Map Smart Transportation Platform, and rainfall data, derived from NASA's global precipitation measurement, are utilized. Traffic vulnerability index, traffic resilience index, and the corresponding quantitative methods are proposed, and the analysis results are presented. This study is of value in improving the understanding of urban traffic vulnerability and resilience, and in enabling the quantitative evaluation of them in urban health assessment and the Healthy Cities program.

Reduction of Human Mobility Matters during Early COVID-19 Outbreaks: Evidence from India, Japan and China.

Mobility restrictions have been a heated topic during the global pandemic of coronavirus disease 2019 (COVID-19). However, multiple recent findings have verified its importance in blocking virus spread. Evidence on the association between mobility, cases imported from abroad and local medical resource supplies is limited. To reveal the association, this study quantified the importance of inter- and intra-country mobility in containing virus spread and avoiding hospitalizations during early stages of COVID-19 outbreaks in India, Japan, and China. We calculated the time-varying reproductive number (Rt) and duration from illness onset to diagnosis confirmation (Doc), to represent conditions of virus spread and hospital bed shortages, respectively. Results showed that inter-country mobility fluctuation could explain 80%, 35%, and 12% of the variance in imported cases and could prevent 20 million, 5 million, and 40 million imported cases in India, Japan and China, respectively. The critical time for screening and monitoring of imported cases is 2 weeks at minimum and 4 weeks at maximum, according to the time when the Pearson's Rs between Rt and imported cases reaches a peak (>0.8). We also found that if local transmission is initiated, a 1% increase in intra-country mobility would result in 1430 (±501), 109 (±181), and 10 (±1) additional bed shortages, as estimated using the Doc in India, Japan, and China, respectively. Our findings provide vital reference for governments to tailor their pre-vaccination policies regarding mobility, especially during future epidemic waves of COVID-19 or similar severe epidemic outbreaks.

Using Internet Search Queries to Assess Public Awareness of the Healthy Cities Approach: A Case Study in Shenzhen, China.

Cities around the globe are embracing the Healthy Cities approach to address urban health challenges. Public awareness is vital for successfully deploying this approach but is rarely assessed. In this study, we used internet search queries to evaluate the public awareness of the Healthy Cities approach applied in Shenzhen, China. The overall situation at the city level and the intercity variations were both analyzed. Additionally, we explored the factors that might affect the internet search queries of the Healthy Cities approach. Our results showed that the public awareness of the approach in Shenzhen was low. There was a high intercity heterogeneity in terms of interest in the various components of the Healthy Cities approach. However, we did not find a significant effect of the selected demographic, environmental, and health factors on the search queries. Based on our findings, we recommend that the city raise public awareness of healthy cities and take actions tailored to health concerns in different city zones. Our study showed that internet search queries can be a valuable data source for assessing the public awareness of the Healthy Cities approach.

[Research advances in chemical constituents and hepatoprotective effect of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus].

Schisandrae has a long history of medicinal use in China. Domestic and foreign scholars have isolated a variety of chemical constituents from Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus, including lignans, volatile oils, polysaccharides, triterpenoids, organic acids, amino acids and so on. Pharmacological studies have shown that their alcohol extracts, water extracts, lignan monomers and polysaccharides could protect liver injury and reduce enzyme ability by a variety of hepatoprotective effects such as enzyme reducing, liver protecting, and antioxidant effect. In this paper, the researches on the chemical composition, hepatoprotective effect and pharmacokinetics of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus in the past forty years were systematically collated, in order to provide useful enlightenment for the clinical application and new drug development of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus in liver protection.

Fault detection and isolation using relative information for multi-agent systems.

We study fault detection and isolation of multi-agent systems existing fault signals. Based upon the designing idea of unknown input observer, we proposed an innovative fault detection and isolation strategy. When the existence conditions are satisfied, the observer can be constructed using only relative information. A threshold logic and the corresponding algorithm are presented to detect and isolate the agent suffering from fault. Furthermore, a distributed implementation of our method is provided which helps to reduce the observer dimensions and simplify the design procedure. Practical simulations are given to demonstrate the validity of the theoretic results.

Global aerosol vertical structure analysis by clustering gridded CALIOP aerosol profiles with fuzzy k-means.

Aerosol vertical structures are critical to understanding distribution and source-sink patterns of aerosol on a large scale. In this study, we carried out spatial clustering analysis for 10-years long CALIOP aerosol profiles with a fuzzy k-means (FKM) method. Raw and normalized data sets were both classified into three representative clusters. Raw aerosol profiles of original data described both aerosol density and structure patterns, which were classified into polluted cluster, medium cluster and clean cluster with visual inspection. The mean aerosol extinction coefficient values in near surface from large to small respectively belonged to polluted cluster, medium cluster and clean cluster. As altitude increased, mean aerosol extinction coefficients of polluted cluster were in rapid decline trend from surface to upper atmosphere. In comparison, there was a slower decrease speed for the aerosol extinction coefficient values of mean aerosol profiles of the other two clusters. Aerosol profiles clusters using normalized data could be used to describe aerosol vertical structure patterns. Normalized aerosol profiles were classified into boundary-layer concentrated cluster (boundary cluster), vertically even distributed cluster (v-even cluster) and surface-layer concentrated cluster (surface cluster). The boundary cluster was stable in the low atmosphere with a decline trend upwards, which was spatially corresponds to strong anthropogenic emission and dust regions. The mean normalized extinction coefficient values of v-even cluster were relatively stable in a large vertical range (about 4 km) at regions with relatively weak wind fields. The coefficients of surface cluster were mainly distributed in the near surface with mostly in coastlines and low aerosol optical depth (AOD) regions. The cluster analysis of CALIOP aerosol profiles provided general patterns for global distributions of aerosol profile density and structure.

The Role of Exosomes in the Female Reproductive System and Breast Cancers.

Exosomes are nanoscale extracellular vesicles released by nearly all cell types. Exosomes were originally considered as waste receptacles for discarding unwanted cellular products; however, these organelles are now considered to be important for cell communication by delivering biologically active molecules such as proteins, DNA, non-coding RNA and mRNA. Studies have revealed that exosomes are closely related to several diseases, especially cancers. Exosomes are indispensable for the emergence and progression of tumor. Here, we review the status of research on exosomes in the female reproductive system cancers and breast cancer, focusing on their biological roles in chemical resistance and immune responses, as well as their underlying applications in drug delivery and nanotherapy and as biological markers for tumor diagnosis.