Directed evolution of the fluorescent protein CGP with in situ biosynthesized noncanonical amino acids.

The incorporation of noncanonical amino acids (ncAAs) into proteins can enhance their function beyond the abilities of canonical amino acids and even generate new functions. However, the ncAAs used for such research are usually chemically synthesized, which is expensive and hinders their application on large industrial scales. We believe that the biosynthesis of ncAAs using metabolic engineering and their employment in situ in target protein engineering with genetic code expansion could overcome these limitations. As a proof of principle, we biosynthesized four ncAAs, O-L-methyltyrosine, 3,4-dihydroxy-L-phenylalanine, 5-hydroxytryptophan, and 5-chloro-L-tryptophan using metabolic engineering and directly evolved the fluorescent consensus green protein (CGP) by combination with nine other exogenous ncAAs in Escherichia coli. After screening a TAG scanning library expressing 13 ncAAs, several variants with enhanced fluorescence and stability were identified. The variants CGPV3pMeoF/K190pMeoF and CGPG20pMeoF/K190pMeoF expressed with biosynthetic O-L-methyltyrosine showed an approximately 1.4-fold improvement in fluorescence compared to the original level, and a 2.5-fold improvement in residual fluorescence after heat treatment. Our results demonstrated the feasibility of integrating metabolic engineering, genetic code expansion, and directed evolution in engineered cells to employ biosynthetic ncAAs in protein engineering. These results could further promote the application of ncAAs in protein engineering and enzyme evolution. IMPORTANCE: Noncanonical amino acids (ncAAs) have shown great potential in protein engineering and enzyme evolution through genetic code expansion. However, in most cases, ncAAs must be provided exogenously during protein expression, which hinders their application, especially when they are expensive or have poor cell membrane penetration. Engineering cells with artificial metabolic pathways to biosynthesize ncAAs and employing them in situ for protein engineering and enzyme evolution could facilitate their application and reduce costs. Here, we attempted to evolve the fluorescent consensus green protein (CGP) with biosynthesized ncAAs. Our results demonstrated the feasibility of using biosynthesized ncAAs in protein engineering, which could further stimulate the application of ncAAs in bioengineering and biomedicine.

Genomic and functional diversity of cultivated Bifidobacterium from human gut microbiota.

The genus Bifidobacterium widely exists in human gut and has been increasingly used as the adjuvant probiotics for the prevention and treatment of diseases. However, the functional differences of Bifidobacterium genomes from different regions of the world remain unclear. We here describe an extensive study on the genomic characteristics and function annotations of 1512 genomes (clustered to 849 non-redundant genomes) of Bifidobacterium cultured from human gut. The distribution of some carbohydrate-active enzymes varied among different Bifidobacterium species and continents. More than 36% of the genomes of B. pseudocatenulatum harbored biosynthetic gene clusters of lanthipeptide-class-iv. 99.76% of the cultivated genomes of Bifidobacterium harbored genes of bile salt hydrolase. Most genomes of B. adolescentis, and all genomes of B. dentium harbored genes involved in gamma-aminobutyric acid synthesis. B. longum subsp. infantis were characterized harboring most genes related to human milk oligosaccharide utilization. Significant differences between the distribution of antibiotic resistance genes among different species and continents revealed the importance to use antibiotics precisely in the clinical treatment. Phages infecting Bifidobacterium and horizontal gene transfers occurring in genomes of Bifidobacterium were dependent on species and region sources, and might help Bifidobacterium adapt to the environment. In addition, the distribution of Bifidobacterium in human gut was found varied from different regions of the world. This study represents a comprehensive view of characteristics and functions of genomes of cultivated Bifidobacterium from human gut, and enables clinical advances in the future.

Development and application of an indirect ELISA for detection of antibodies against emerging atypical porcine pestivirus.

BACKGROUND: Atypical porcine pestivirus (APPV) is a newly discovered swine pestivirus, which can cause congenital tremor and high mortality in newborn piglets and subclinical infection in adult pigs, leading to significant impacts on the pig industry. Currently, there is no approved serological method to assess APPV infection status in pig farms. METHODS: In this study, the envelope glycoprotein E2 of APPV was highly expressed in suspension HEK293 cells, and further an indirect enzyme-linked immunosorbent assay based on the recombinant E2 protein (E2-iELISA) was developed and evaluated. RESULTS: The reaction parameters of the E2-iELISA were optimized, and the cutoff value was determined to be 0.2 by analyzing S/P values of 165 negative sera against APPV that were confirmed by virus neutralization test (VNT). Specificity test showed that the method had no cross-reaction with other common swine viruses. The E2-iELISA was evaluated using a panel of swine sera, and showed high sensitivity (113/120, 94.2%) and specificity (65/70, 92.9%), and the agreement rate with VNT was 93.7% (178/190). Subsequently, the E2-iELISA was utilized to investigate the seroprevalence of APPV in pig herds of China. When detecting 1368 pig serum samples collected from nine provinces in China, the overall seroprevalence of APPV was 73.9% (1011/1368). CONCLUSION: Our findings suggest that the E2-iELISA is specific and sensitive, and could be a valuable tool for serological surveillance of APPV infection in pigs.

Effects of Feather Hydrolysates Generated by Probiotic Bacillus licheniformis WHU on Gut Microbiota of Broiler and Common carp.

Due to the ever-increasing demand for meat, it has become necessary to identify cheap and sustainable sources of protein for animal feed. Feathers are the major byproduct of poultry industry, which are rich in hard-to-degrade keratin protein. Previously we found that intact feathers can be digested into free amino acids, short peptides, and nano-/micro-keratin particles by the strain Bacillus licheniformis WHU in water, and the resulting feather hydrolysates exhibit prebiotic effects on mice. To explore the potential utilization of feather hydrolysate in the feed industry, we investigated its effects on the gut microbiota of broilers and fish. Our results suggest that feather hydrolysates significantly decrease and increase the diversity of gut microbial communities in broilers and fish, respectively. The composition of the gut microbiota was markedly altered in both of the animals. The abundance of bacteria with potentially pathogenic phenotypes in the gut microbial community of the fish significantly decreased. Staphylococcus spp., Pseudomonas spp., Neisseria spp., Achromobacter spp. were significantly inhibited by the feather hydrolysates. In addition, feather hydrolysates significantly improved proteolytic activity in the guts of broilers and fish. In fish, the expression levels of ZO-1 and TGF-α significantly improved after administration of feather hydrolysates. The results presented here suggest that feather hydrolysates generated by B. licheniformis WHU could be an alternative protein source in aquaculture and could exert beneficial effects on fish.

PLEIOTROPIC REGULATORY LOCUS1 maintains actin microfilament integrity to regulate pavement cell morphogenesis.

Actin dynamics are critical for plant cell morphogenesis, but the underlying signaling mechanisms regulating these dynamics are not well understood. Here, we established that PLEIOTROPIC REGULATORY LOCUS1 (PRL1) modulates leaf pavement cell (PC) morphogenesis in Arabidopsis (Arabidopsis thaliana) by maintaining the dynamic homeostasis of actin microfilaments (MF). Our previous studies indicated that PC shape was determined by antagonistic RHO-RELATED GTPase FROM PLANTS 2 (ROP2) and RHO-RELATED GTPase FROM PLANTS 6 (ROP6) signaling pathways that promote cortical MF and microtubule organization, respectively. Our genetic screen for additional components in ROP6-mediated signaling identified prl1 alleles. Genetic analysis confirmed that PRL1 plays a key role in PC morphogenesis. Mutations in PRL1 caused cortical MF depolymerization, resulting in defective PC morphogenesis. Further genetic analysis revealed that PRL1 is epistatic to ROP2 and ROP6 in PC morphogenesis. Mutations in PRL1 enhanced the effects of ROP2 and ROP6 in PC morphogenesis, leading to a synergistic phenotype in the PCs of ROP2 prl1 and ROP6 prl1. Furthermore, the activities of ROP2 and ROP6 were differentially altered in prl1 mutants, suggesting that ROP2 and ROP6 function downstream of PRL1. Additionally, cortical MF depolymerization in prl1 mutants occurred independently of ROP2 and ROP6, implying that these proteins impact PC morphogenesis in the prl1 mutant through other cellular processes. Our research indicates that PRL1 preserves the structural integrity of actin and facilitates pavement cell morphogenesis in Arabidopsis.

Identification and characterization of a versatile keratinase, KerZJ, from Stenotrophomonas sp. LMY.

Keratinases have drawn increasing attention in recent decades owing to their catalytic versatility and broad applications from agriculture to medicine. In the present study, we isolated a highly keratinolytic and fibrinolytic bacterium from the campus soil and named it Stenotrophomonas sp. LMY based on genetic information. To identify the potential keratinase genes, the genome sequence of the strain was obtained and analyzed. Sequence alignment and comparison revealed that the protein 1_737 (KerZJ) had the highest sequence homology to a reported keratinase KerBL. We recombinantly expressed KerZJ in Escherichia coli Origami™ (DE) pLysS and purified it to homogeneity. KerZJ showed the highest activity at 40 °C and pH 9.0, and metal ions exhibited no significant effects on its activity. Although reducing agents would break the disulfide bonds in KerZJ and reduce its activity, KerZJ still exhibited the ability to hydrolyze feather keratin in the presence of ß-ME. KerZJ could efficiently digest human prion proteins. In addition, KerZJ showed fibrinolytic activity on fibrin plates and effectively eliminated blood clots in a thrombosis mouse model without side effects. Our results suggest that KerZJ is a versatile keratinase with significant potential for keratin treatment, decontamination of prions, and fibrinolytic therapy.

Isolation and Molecular Characterization of Atypical Porcine Pestivirus Emerging in China.

Atypical porcine pestivirus (APPV) is a recently discovered and very divergent species of the genus Pestivirus within the family Flaviviridae, which causes congenital tremor (CT) in newborn piglets. In this study, an APPV epidemiological investigation was conducted by studying 975 swine samples (562 tissue and 413 serum samples) collected from different parts of China from 2017 to 2021. The results revealed that the overall positive rate of the APPV genome was 7.08% (69/975), among which 50.7% (35/69) of the samples tested positive for one or more other common swine viruses, especially porcine circovirus type 2 (PCV2) with a coinfection rate of 36.2% (25/69). Subsequently, a novel APPV strain, named China/HLJ491/2017, was isolated in porcine kidney (PK)-15 cells for the first time from a weaned piglet that was infected with both APPV and PCV2. The new APPV isolate was confirmed by RT-PCR, sequencing, immunofluorescence assay, and transmission electron microscopy. After clearing PCV2, a pure APPV strain was obtained and further stably propagated in PK-15 cells for more than 30 passages. Full genome sequencing and phylogenetic analysis showed that the China/HLJ491/2017 strain was classified as genotype 2, sharing 80.8 to 97.6% of its nucleotide identity with previously published APPV strains. In conclusion, this study enhanced our knowledge of this new pestivirus and the successful isolation of the APPV strain provides critical material for the investigation of the biological and pathogenic properties of this emerging virus, as well as the development of vaccines and diagnostic reagents.

Use of non-canonical amino acids in genetic code expansion-based therapeutics: Effects on mouse gut microbiota.

Vaccines and cell therapeutics based on genetic code expansion are emerging. A crucial step in these therapeutic technologies is the oral administration of non-canonical amino acids (ncAAs) to control pathogen growth and therapeutic protein levels in vivo. Investigating the toxicity effects of ncAAs can help identify more suitable candidates for developing genetic code expansion-based vaccines and cell therapeutics. In this study, we determined the effects of three ncAAs, namely, 4-acetyl-phenylalanine (pAcF), 4-iodo-phenylalanine (pIoF), and 4-methoxy-phenylalanine (pMeoF), commonly used in genetic code expansion-based vaccines and cell therapeutics, on the main organs, serum biochemical parameters, and gut microbiota in mice. We observed that pIoF and pMeoF significantly altered serum biochemical parameters to some extent. Moreover, the alterations in the mouse gut microbial composition were considerably greater after the oral administration of pIoF and pMeoF than after that of pAcF, compared with that in the control mice. These findings suggest that pAcF is more suitable than pIoF and pMeoF for application in genetic code expansion-based vaccines and cell therapeutics as it disturbs the physiological and gut microecological balance in mice to a lesser extent.

Bioconversion of feather waste into bioactive nutrients in water by Bacillus licheniformis WHU.

Feathers become hazardous pollutants when deposited directly into the environment. The rapid expansion of the poultry industry has significantly increased feather waste, necessitating the development of new ways to degrade and utilize feathers. This study investigated the ability of Bacillus licheniformis WHU to digest intact chicken feathers in water. The results indicated that yields of free amino acids, bioactive peptides, and keratin-derived nano-/micro-particles were improved in bacteria- versus purified keratinase-derived feather hydrolysate. Bacteria-derived feather hydrolysate supplementation induced health benefits in mice, including significantly increased intestinal villus height and zonula occludens-1 protein expression, as well as increased secretory immunoglobulin A levels in the intestinal mucosa and superoxide dismutase activity in serum. Additionally, feather hydrolysate supplementation modulated the mouse gut microbiota, reflected by increased relative abundance of probiotics such as Lactobacillus spp., decreased relative abundance of Proteobacteria at the phylum level and pathogens such as Staphylococcus spp., and increased Bacteroidota/Firmicutes ratio. This study developed a simple, cost-effective method to degrade feathers by B. licheniformis WHU digestion, yielding a hydrolysate that can be directly used as a bioactive nutrient resource. The study findings have applications in the livestock, poultry, and aquaculture industries, which have high demands for cheap protein. KEY POINTS: • Bacillus licheniformis could degrade intact feather in water. • The resulting feather hydrolysate shows prebiotic effects on mouse.

Characteristics of brittle cornea syndrome by multimodal imaging modalities: a case report.

BACKGROUND: A report of a Brittle cornea syndrome (BCS) case with bluish scleral discoloration, keratoglobus, and myopia based on multimodal imaging modalities including in vivo confocal microscopy (IVCM), high-definition optical coherence tomography (HD-OCT) and scheimpflug corneal densitometry analysis. CASE PRESENTATION: A 36-year-old Chinese female patient presented with significant bluish discoloration of the sclera in both eyes, extreme corneal thinning with increased corneal curvature, increased central corneal densitometry, and nystagmus. She also had scoliosis, severe osteoporosis, and thyroid disease. CONCLUSIONS: Timely diagnosis, early detection, and detailed follow-up are essential for BCS. There has been no report of a BCS evaluation performed by IVCM and corneal densitometry methods thus far in the literature. Furthermore, multimodal imaging can offer a more comprehensive view of BCS and contribute to a deeper understanding of the disease. Interestingly, this is a rare case of BCS in an adult with good vision, an intact cornea, and nystagmus.

Multi-View Clustering for Integration of Gene Expression and Methylation Data With Tensor Decomposition and Self-Representation Learning.

The accumulated DNA methylation and gene expression provide a great opportunity to exploit the epigenetic patterns of genes, which is the foundation for revealing the underlying mechanisms of biological systems. Current integrative algorithms are criticized for undesirable performance because they fail to address the heterogeneity of expression and methylation data, and the intrinsic relations among them. To solve this issue, a novel multi-view clustering with self-representation learning and low-rank tensor constraint (MCSL-LTC) is proposed for the integration of gene expression and DNA methylation data, which are treated as complementary views. Specifically, MCSL-LTC first learns the low-dimensional features for each view with the linear projection, and then these features are fused in a unified tensor space with low-rank constraints. In this case, the complementary information of various views is precisely captured, where the heterogeneity of omic data is avoided, thereby enhancing the consistency of different views. Finally, MCSL-LTC obtains a consensus cluster of genes reflecting the structure and features of various views. Experimental results demonstrate that the proposed approach outperforms state-of-the-art baselines in terms of accuracy on both the social and cancer data, which provides an effective and efficient method for the integration of heterogeneous genomic data.

Sensing dynamic human activity zones using geo-tagged big data in Greater London, UK during the COVID-19 pandemic.

Exploration of dynamic human activity gives significant insights into understanding the urban environment and can help to reinforce scientific urban management strategies. Lots of studies are arising regarding the significant human activity changes in global metropolises and regions affected by COVID-19 containment policies. However, the variations of human activity dynamics amid different phases divided by the non-pharmaceutical intervention policies (e.g., stay-at-home, lockdown) have not been investigated across urban areas in space and time and discussed with the urban characteristic determinants. In this study, we aim to explore the influence of different restriction phases on dynamic human activity through sensing human activity zones (HAZs) and their dominated urban characteristics. Herein, we proposed an explainable analysis framework to explore the HAZ variations consisting of three parts, i.e., footfall detection, HAZs delineation and the identification of relationships between urban characteristics and HAZs. In our study area of Greater London, United Kingdom, we first utilised the footfall detection method to extract human activity metrics (footfalls) counted by visits/stays at space and time from the anonymous mobile phone GPS trajectories. Then, we characterised HAZs based on the homogeneity of daily human footfalls at census output areas (OAs) during the predefined restriction phases in the UK. Lastly, we examined the feature importance of explanatory variables as the metric of the relationship between human activity and urban characteristics using machine learning classifiers. The results show that dynamic human activity exhibits statistically significant differences in terms of the HAZ distributions across restriction phases and is strongly associated with urban characteristics (e.g., specific land use types) during the COVID-19 pandemic. These findings can improve the understanding of the variation of human activity patterns during the pandemic and offer insights into city management resource allocation in urban areas concerning dynamic human activity.

Novel n-i CeO2/a-Al2O3 Heterostructure Electrolyte Derived from the Insulator a-Al2O3 for Fuel Cells.

Heterostructure technologies have been regarded as promising methods in the development of electrolytes with high ionic conductivity for low-temperature solid oxide fuel cells (LT-SOFCs). Here, a novel semiconductor/insulator (n-i) heterostructure strategy has been proposed to develop composite electrolytes for LT-SOFCs based on CeO2 and the insulator amorphous alumina (a-Al2O3). The constructed CeO2/a-Al2O3 electrolyte exhibits an ionic conductivity of up to 0.127 S cm-1, and its fuel cell achieves a maximum power density (MPD) of 1017 mW cm-2 with an open-circuit voltage (OCV) of 1.14 V at 550 °C without the short-circuiting problem, suggesting that the introduction of a-Al2O3 can effectively suppress the electron conduction of CeO2. It is found that the potential energy barrier at the heterointerfaces caused by the ultrawide band gap of the insulator a-Al2O3 plays an important role in restraining electron conduction. Simultaneously, the thermoelectric effect of the insulator induces more oxygen vacancies because of interface charge compensation, which further promotes ionic transport and results in high ionic conductivity and fuel cell performance. This study presents a practical n-i heterostructure electrolyte design, and further research confirmed the advanced functionality of the CeO2/a-Al2O3 electrolyte. Our study may open frontiers in the field of developing high-efficiency electrolytes of LT-SOFCs using insulating materials such as amorphous alumina.

Spatial-temporal characteristics and influencing factors of county-level carbon emissions in Zhejiang Province, China.

Zhejiang Province is a "demonstration area for high-quality development and construction of common prosperity" in China. Moreover, the county is the basic unit and power source for the economic development of Zhejiang Province. Therefore, the research on the spatial-temporal characteristics and influencing factors of county-level carbon emissions is of great significance for Zhejiang Province to achieve the strategic goal of carbon peak and carbon neutrality. Based on the carbon emissions and socio-economic data of 62 counties in Zhejiang Province from 2014 to 2020, the spatial dependence and agglomeration of county-level carbon emissions are analyzed through the spatial autocorrelation test and local spatial autocorrelation test respectively. According to the spatial-temporal characteristics of county-level carbon emissions revealed by the index of Moran's I and local Moran's I, the spatial error STIRPAT model is used to study the influencing factors of county-level carbon emissions in Zhejiang Province, China. The main results are as follows: (1) The total amount of county-level carbon emissions of 62 counties fluctuates from 259.69 to 326.28 million tons and shows a growth trend. (2) Moran's I index is between 0.369 and 0.399. The county-level carbon emissions have a significant spatial correlation, and the spatial agglomeration trend is relatively stable, which is consistent with the hypothesis of the geographical polarization effect. (3) High-high agglomeration counties are concentrated in the northeast of Zhejiang Province, while low-low agglomeration counties are mainly in the southwest. (4) The relationship between county per capita GDP and carbon emissions has not been "decoupled," because when other variables remain unchanged, the county's total carbon emissions will increase by 2.866% for every 1% increase in the county's per capita GDP; the increase of the proportion of secondary industry contributes to the decline of carbon emissions, and the low-carbon effect brought by large-scale industrial development as well as scientific and technological innovation has not yet appeared. (5) The estimate of the spatial coefficient λ was 0.324, which illustrates that the carbon emission of a single county is positively affected by the carbon emission of the neighboring counties, and other socio-economic factors affecting carbon emission among counties also have a spatial correlation. Therefore, the policy of realizing regional coordinated development as well as the carbon peaking and carbon neutrality goals should not only focus on industrial layout, but also take a dynamic and comprehensive consideration from a spatial perspective.

Nattokinase enhances the preventive effects of Escherichia coli Nissle 1917 on dextran sulfate sodium-induced colitis in mice.

Nattokinase with excellent anti-thrombotic, anti-inflammatory, anti-tumor, and anti-hypertension properties has been used in the development of several healthcare products in many countries. The probiotic Escherichia coli Nissle 1917 (EcN) with anti-inflammatory effect is commonly used to treat inflammatory bowel disease. To determine whether nattokinase could enhance the therapeutic efficacy of EcN in colitis, a recombinant E. coli Nissle 1917 strain (EcNnatto) with nattokinase-expressing ability was successfully constructed, and the protective effect of the engineered strain on mice with experimental chronic colitis was investigated. Although both EcN and EcNnatto strains substantially alleviated the clinical symptoms and pathological abnormalities in colitis mice by regulating gut flora and maintaining intestinal barrier function, the EcNnatto strain was found to perform better than the control strain, based on a further increase in colon length and a downregulation in pro-inflammatory cytokines (IL-6 and TNF-α). Nattokinase expressed in EcN attenuated DSS-induced epithelial damage and restored the mucosal integrity by upregulating the levels of tight junction proteins, including ZO-1 and occludin. The expression level of Lgr5, a marker of intestinal stem cells, was also increased. Moreover, constitutively expressed nattokinase in EcN reversed the gut microbial richness and diversity in colitis mice. Based on our findings, nattokinase could strengthen the capacity of EcN to treat intestinal inflammation.

Time-Resolved Proteomics of Germinating Spores of Bacillus cereus.

Bacillus cereus is a spore-forming human pathogen that is a burden to the food chain. Dormant spores are highly resistant to harsh environmental conditions, but lose resistance after germination. In this study, we investigate the B. cereus spore proteome upon spore germination and outgrowth so as to obtain new insights into the molecular mechanisms involved. We used mass spectrometry combined with co-expression network analysis and obtained a unique global proteome view of the germination and outgrowth processes of B. cereus spores by monitoring 2211 protein changeovers. We are the first to examine germination and outgrowth models of B. cereus spores experimentally by studying the dynamics of germinant receptors, other proteins involved in spore germination and resistance, and coat and exosporium proteins. Furthermore, through the co-expression analysis of 1175 proteins identified with high quality data, germination proteome data were clustered into eight modules (termed black, blue, brown, green, red, turquoise, grey, and yellow), whose associated functions and expression profiles were investigated. Germination related proteins were clustered into blue and brown modules, the abundances of which decreased after finishing germination. In the brown and blue we identified 124 proteins that could be vital during germination. These proteins will be very interesting to study in future genetic studies regarding their function in spore revival in B. cereus.

Changes in the Spore Proteome of Bacillus cereus in Response to Introduction of Plasmids.

Fluorescent fusion proteins were expressed in Bacillus cereus to visualize the germinosome by introducing a plasmid that carries fluorescent fusion proteins of germinant receptor GerR subunits or germinosome scaffold protein GerD. The effects of plasmid insertion and recombinant protein expression on the spore proteome were investigated. Proteomic analysis showed that overexpression of the target proteins had negligible effects on the spore proteome. However, plasmid-bearing spores displayed dramatic abundance changes in spore proteins involved in signaling and metabolism. Our findings indicate that the introduction of a plasmid alone alters the spore protein composition dramatically, with 993 proteins significantly down-regulated and 415 proteins significantly up-regulated among 3323 identified proteins. This shows that empty vector controls are more appropriate to compare proteome changes due to plasmid-encoded genes than is the wild-type strain, when using plasmid-based genetic tools. Therefore, researchers should keep in mind that molecular cloning techniques can alter more than their intended targets in a biological system, and interpret results with this in mind.

Spatio-temporal stratified associations between urban human activities and crime patterns: a case study in San Francisco around the COVID-19 stay-at-home mandate.

Crime changes have been reported as a result of human routine activity shifting due to containment policies, such as stay-at-home (SAH) mandates during the COVID-19 pandemic. However, the way in which the manifestation of crime in both space and time is affected by dynamic human activities has not been explored in depth in empirical studies. Here, we aim to quantitatively measure the spatio-temporal stratified associations between crime patterns and human activities in the context of an unstable period of the ever-changing socio-demographic backcloth. We propose an analytical framework to detect the stratified associations between dynamic human activities and crimes in urban areas. In a case study of San Francisco, United States, we first identify human activity zones (HAZs) based on the similarity of daily footfall signatures on census block groups (CBGs). Then, we examine the spatial associations between crime spatial distributions at the CBG-level and the HAZs using spatial stratified heterogeneity statistical measurements. Thirdly, we use different temporal observation scales around the effective date of the SAH mandate during the COVID-19 pandemic to investigate the dynamic nature of the associations. The results reveal that the spatial patterns of most crime types are statistically significantly associated with that of human activities zones. Property crime exhibits a higher stratified association than violent crime across all temporal scales. Further, the strongest association is obtained with the eight-week time span centred around the SAH order. These findings not only enhance our understanding of the relationships between urban crime and human activities, but also offer insights into that tailored crime intervention strategies need to consider human activity variables.

Oral Administration of 5-Hydroxytryptophan Restores Gut Microbiota Dysbiosis in a Mouse Model of Depression.

5-Hydroxytryptophan (5-HTP) has positive clinical effects on various neuropsychiatric and metabiotic disorders, especially depression. Although it increases serotonin levels in the brain and gastrointestinal tract, its pharmacology remains largely unknown. Our goal was to determine the effects of 5-HTP on the mouse gut microbiome, which has a close relationship with depression through the "microbiota-gut-brain axis." We confirmed that depressive disorder restructures the gut microbial community, and 5-HTP efficiently improves depressive symptoms in mice. Oral administration of 5-HTP significantly restored gut microbiota dysbiosis in mice with depression-like behaviors. The diversity and richness of gut microbial communities and relative abundance of specific microbial taxa at both phylum and genus levels were partially recovered. 5-HTP exhibited some positive effects on restoring the alterations in the concentrations of short-chain fatty acids and brain-derived neurotrophic factors caused by depression in mice. Our results may provide new insights into the pharmacology of 5-HTP in treating depression and other disorders.

Measures to prevent nosocomial transmissions of COVID-19 based on interpersonal contact data.

BACKGROUND: With the global spreading of Coronavirus disease (COVID-19), many primary care medical workers have been infected, particularly in the early stages of this pandemic. Although extensive studies have explored the COVID-19 transmission patterns and (non-) pharmaceutical intervention to protect the general public, limited research has analysed the measures to prevent nosocomial transmission based upon detailed interpersonal contacts between medical staff and patients. AIM: This paper aims to develop and evaluate proactive prevention measures to contain the nosocomial transmission of COVID-19. The specific objectives are (1) to understand the virus transmission via interpersonal contacts among medical staff and patients; (2) to define proactive measures to reduce the risk of infection of medical staff and (3) evaluate the effectiveness of these measures to control the COVID-19 epidemic in hospitals. METHODS: We observed the operation of a typical primary hospital in China to understand the interpersonal contacts among medical staff and patients. We defined effective distance as the indicator for risk of transmission. Then three proactive measures were proposed based upon the observations, including a medical staff rotation system, the establishment of a separate fever clinic and medical staff working alone. Finally, the impacts of these measures are evaluated with a modified Susceptible-Exposure-Infected-Removed model accommodating the situation of hospitals and asymptomatic and latent infection of COVID-19. The case study was conducted with the hospital observed in December 2019 and February 2020. FINDINGS: The implementation of the medical staff rotation system has the most significant impact on containing the epidemic. The establishment of a separate fever clinic and medical staff working alone also benefits from inhibiting the epidemic outbreak. The simulation finds that if effective prevention and control measures are not taken in time, it will lead to a surge of infection cases in all asymptomatic probabilities and incubation periods.