Search

Currently, almost all known regulators involved in bacterial phosphorus metabolism are proteins. In this study, we identified a conserved new small regulatory RNA (sRNA), named PhoS, encoded in the 3' untranslated region (UTR) of the phoPR genes in Bacillus velezensis and B. subtilis. Expression of phoS is strongly induced upon phosphorus scarcity and stimulated by the transcription factor PhoP. Conversely, PhoS positively regulates PhoP translation by binding to the ribosome binding site (RBS) of phoP mRNA. PhoS can promote Bacillus biofilm formation through, at least in part, enhancing the expression of the matrix-related genes, such as the eps genes and the tapA-sipW-tasA operon. The positive regulation of phoP expression by PhoS contributes to the promoting effect of PhoS on biofilm formation. sRNAs regulating biofilm formation have rarely been reported in gram-positive Bacillus species. Here we highlight the significance of sRNAs involved in two important biological processes: phosphate metabolism and biofilm formation., (© 2024. The Author(s).)

Radiographic landmark annotation determines patients' anatomical parameters and influences diagnoses. However, challenges arise from ambiguous region-based definitions, human error, and image quality variations, potentially compromising patient care. Additionally, AI landmark localization often presents its predictions in a probability-based heatmap format, which lacks a corresponding clinical standard for accuracy validation. This Data Descriptor presents a clinical benchmark dataset for pelvic tilt landmarks, gathered through a probabilistic approach to measure annotation accuracy within clinical environments. A retrospective analysis of 115 pelvic sagittal radiographs was conducted for annotating pelvic tilt parameters by five annotators, revealing landmark cloud sizes of 6.04 mm-17.90 mm at a 95% dataset threshold, corresponding to 9.51°-16.55° maximum angular disagreement in clinical settings. The outcome provides a quantified point cloud dataset for each landmark corresponding to different probabilities, which enables assessment of directional annotation distribution and parameter-wise impact, providing clinical benchmarks. The data is readily reusable for AI studies analyzing the same landmarks, and the method can be easily replicated for establishing clinical accuracy benchmarks of other landmarks., (© 2024. The Author(s).)

How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derived Slamf9 + macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9 + macrophages contain SARS-CoV-2, recruit and interact with Isg12 + Cst7 + neutrophils to clear the viruses. After viral clearance, Slamf9 + macrophages differentiate into Trem2 + and Fbp1 + macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role of Slamf9 + macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution., (© 2024. The Author(s).)

How immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell-T cell immunity hubs, where Ccr7 + Ido1 + dendritic cells, Cd160 + Cd8 + T cells, and Tnfrsf4 + Cd4 + T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9 + macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity., (© 2024. The Author(s).)

The neighborhood effect has become an important framework with which to study the mechanisms that maintain the coexistence of tree species. Phylogenetic relatedness among neighboring plants directly affects species coexistence and the maintenance of tree diversity. And some studies have reported that seedling performance is negatively correlated with phylogenetic relatedness, which termed phylogenetic negative density dependence. Soil-borne fungal pathogens affected seedling performance of phylogenetically related host species, i.e., phylogenetic Janzen-Connell effect. Seedlings may be particularly vulnerable to habitat and neighbor characteristics. Although previous studies have demonstrated the influence of neighborhood effects, phylogenetic relatedness, and habitat filtering on seedling survival, growth, and mortality, the effect of variation in these factors on seedling abundance remains unclear. To address this question, we used a 4-ha (200 m × 200 m) and monitored four-year (2020-2023) seedling dataset from a mid-montane humid evergreen broad-leaved subtropical forest in the Gaoligong Mountains, Yunnan, Southwestern China, and which consisted of 916 seedlings belonging to 56 species. The results of generalized linear mixed models showed no significant effect of conspecific adult neighbors on seedling abundance at any of the intervals evaluated. In contrast, we found evidence of phylogenetic distance density dependence in the forests of the Gaoligong Mountains. Specifically, there was a significant positive effect of the relative average phylogenetic distance between heterospecific adult neighbors and focal seedlings on focal seedling abundance in 2020; however, the relative average phylogenetic distance between heterospecific seedling neighbors and focal seedlings had a significant negative effect on seedling abundance over the four-year period (2020-2023). Among the habitat factors, only light (canopy opening) had a negative effect on seedling abundance in all four years. Light resources may be a limiting factor for seedlings, and determine seedling dynamics in subtropical forests. Overall, our results demonstrated that phylogenetic density dependence and habitat filtering affected subtropical seedling abundance. Our findings provide new evidence of the impact of phylogenetic density dependence on seedling abundance in a subtropical mid-montane humid evergreen broad-leaved forest and highlight the need to incorporate the neighborhood effect, phylogenetic relatedness, and habitat factors in models assessing seedling abundance., (© 2024. The Author(s).)

Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, the mechanisms governing metastasis are not fully elucidated. Contemporary findings in the domain of cancer biology have shed light on the molecular aspects of this intricate process. Tumor cells undergoing invasion engage with other cellular entities and proteins en route to their destination. Insights into these engagements have enhanced our comprehension of the principles directing the movement and adaptability of metastatic cells. The tumor microenvironment plays a pivotal role in facilitating the invasion and proliferation of cancer cells by enabling tumor cells to navigate through stromal barriers. Such attributes are influenced by genetic and epigenetic changes occurring in the tumor cells and their surrounding milieu. A profound understanding of the metastatic process's biological mechanisms is indispensable for devising efficacious therapeutic strategies. This review delves into recent developments concerning metastasis-associated genes, important signaling pathways, tumor microenvironment, metabolic processes, peripheral immunity, and mechanical forces and cancer metastasis. In addition, we combine recent advances with a particular emphasis on the prospect of developing effective interventions including the most popular cancer immunotherapies and nanotechnology to combat metastasis. We have also identified the limitations of current research on tumor metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers and early detection methods, as well as heterogeneity among others. It is anticipated that this comprehensive review will significantly contribute to the advancement of cancer metastasis research., (© 2024. The Author(s).)

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1 + T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans., (© 2024. The Author(s).)

Metallurgical dust and sludge are solid waste resources with recycling value. In recent years, rotary hearth furnace has become the most important means to treat metallurgical dust and sludge because of its wide range of raw materials and strong treatment capacity. In this study blast furnace ash and converter sludge were selected as the research objects, and high-quality metallized pellets were prepared based on the rotary hearth furnace process. The strength changed of pellets, the reduction process of iron oxides and the removal process of zinc during the roasting of pellets in rotary hearth furnace were studied. To explore the reasonable roasting condition for preparing metallized pellets in rotary hearth furnace. The optimum roasting temperature of the pellets was 1250℃ and the roasting time was 25 min. The compressive strength, metallization rate and dezincification rate of metallized pellets reached 1361N, 97.44% and 95.67%, respectively. The efficient resource utilization of various metallurgical dust and sludge is realized., (© 2024. The Author(s).)

A Josephson radiation threshold detector (JRTD) that is based on the threshold behaviour of a current bias Josephson junction (CBJJ) is designed and fabricated for infrared radiation (IR@1550nm) detection at low temperatures. To achieve the optimal performance, we develop a binary hypothesis detection method to calibrate Josephson threshold behaviours (i.e. the switching current distributions of the CBJJ with the Al/AlO x /Al junction) in the absence and presence of radiation. In the absence of IR radiation, the junction transitioned with a measurable voltage drop across the junction, and this signal was treated as the events of hypothesis H 0 . The events of junction transition observed in the presence of the IR radiation served as hypothesis H 1 . Considering the usual Gaussian noise and based on statistical decision theory, the accumulated data of the measured switching current distributions are processed, and the threshold sensitivity of the demonstrated JRTD device is estimated. The minimum detectable IR radiation power of the proposed detector is approximately 0.74 pW, which corresponds to the photon rate of 5.692 × 10 6 photons/second. Further optimisation of JRTDs to implement the desired binary detection of a single photon is still a subject of argument, at least theoretically., (© 2024. The Author(s).)

Lung adenocarcinoma (LUAD) remains an incurable disease with a poor prognosis. This study aimed to explore neutrophil‑related genes (NRGs) and develop a prognostic signature for predicting the prognosis of LUAD. NRGs were obtained by intersecting modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data and the marker genes of neutrophils identified from single-cell RNA-sequencing(scRNA-seq) data. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were run to construct a prognostic signature, follow by delineation of risk groups, and external validation. Analyses of ESTIMAT, immune function, Tumor Immune Dysfunction and Exclusion (TIDE) scores, Immune cell Proportion Score (IPS), and immune checkpoint genes between high- and low-risk groups were performed, and then analyses of drug sensitivity to screen for sensitive anticancer drugs in high-risk groups. A total of 45 candidate NRGs were identified, of which PLTP, EREG, CD68, CD69, PLAUR, and CYP27A1 were considered to be significantly associated with prognosis in LUAD and were used to construct a prognostic signature. Correlation analysis showed significant differences in the immune landscape between high- and low-risk groups. In addition, our prognostic signature was important for predicting drug sensitivity in the high-risk group. Our study screened for NRGs in LUAD and constructed a novel and effective signature, revealing the immune landscape and providing more appropriate guidance protocols in LUAD treatment., (© 2023. Springer Nature Limited.)

Promoting well-being is one of the key targets of the Sustainable Development Goals at the United Nations. Many national and city governments worldwide are incorporating Subjective Well-Being (SWB) indicators into their agenda, to complement traditional objective development and economic metrics. In this study, we introduce the Twitter Sentiment Geographical Index (TSGI), a location-specific expressed sentiment database with SWB implications, derived through deep-learning-based natural language processing techniques applied to 4.3 billion geotagged tweets worldwide since 2019. Our open-source TSGI database represents the most extensive Twitter sentiment resource to date, encompassing multilingual sentiment measurements across 164 countries at the admin-2 (county/city) level and daily frequency. Based on the TSGI database, we have created a web platform allowing researchers to access the sentiment indices of selected regions in the given time period., (© 2023. Springer Nature Limited.)

Salidroside is a natural product of phenols, which has a wide scape of pharmacological effects, but its pharmacological effects and molecular mechanism on endometrial cancer are not clear. To systematically explore the pharmacological effects and molecular mechanisms of salidroside on endometrial cancer through the method of network pharmacology. The possible target genes of salidroside were obtained through different pharmacological databases and analysis platforms, and then the relevant target genes of endometrial cancer were obtained through the GeneCards website, and the target genes were uniformly converted into standardized gene names with Uniprot. The collected data were then processed to obtain common target genes and further analyzed through the String website to construct a protein-protein interaction (PPI) network, followed by gene ontology (GO) functional annotation and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analysis. We further interpreted the molecular mechanism of salidroside for the treatment of endometrial cancer by constructing a "drug component-target gene-disease" network. Finally, we performed molecular docking to validate the binding conformation between salidroside and the candidate target genes. There were 175 target genes of salidroside after normalization, among which 113 target genes interacted with endometrial cancer. GO analysis indicated that the anti-endometrial cancer effect of salidroside may be strongly related to biological processes such as apoptosis and response to drug. KEGG analysis indicated that its mechanism may be related to pathway in cancer and PI3K-AKT signaling pathway. Molecular docking showed that salidroside had high affinity with five key genes. Based on the novel network pharmacology and molecular docking validation research methods, we have revealed for the first time the potential mechanism of salidroside in the therapy of endometrial cancer., (© 2023. Springer Nature Limited.)

Vaccination with different vaccines has been implemented globally to counter the continuous COVID-19 pandemic. However, the vaccine-elicited antibodies have reduced efficiency against the highly mutated Omicron sub-variants. Previously, we developed a protein subunit COVID-19 vaccine called ZF2001, based on the dimeric receptor-binding domain (RBD). This vaccine has been administered using different dosing intervals in real-world setting. Some individuals received three doses of ZF2001, with a one-month interval between each dose, due to urgent clinical requirements. Others had an extended dosing interval of up to five months between the second and third dose, a standard vaccination regimen for the protein subunit vaccine against hepatitis B. In this study, we profile B cell responses in individuals who received three doses of ZF2001, and compared those with long or short dosing intervals. We observed that the long-interval group exhibited higher and broader serologic antibody responses. These responses were associated with the increased size and evolution of vaccine-elicited B-cell receptor repertoires, characterized by the elevation of expanded clonotypes and somatic hypermutations. Both groups of individuals generated substantial amounts of broadly neutralizing antibodies (bnAbs) against various SARS-CoV-2 variants, including Omicron sub-variants such as XBB. These bnAbs target four antigenic sites within the RBD. To determine the vulnerable site of SARS-CoV-2, we employed cryo-electron microscopy to identify the epitopes of highly potent bnAbs that targeted two major sites. Our findings provide immunological insights into the B cell responses elicited by RBD-based vaccine, and suggest that a vaccination regimen of prolonging time interval should be used in practice., (© 2023. The Author(s).)

Pulcherrimin is an iron-binding reddish pigment produced by various bacterial and yeast species. In the soil bacterium Bacillus subtilis, this pigment is synthesized intracellularly as the colorless pulcherriminic acid by using two molecules of tRNA-charged leucine as the substrate; pulcherriminic acid molecules are then secreted and bind to ferric iron extracellularly to form the red-colored pigment pulcherrimin. The biological importance of pulcherrimin is not well understood. A previous study showed that secretion of pulcherrimin caused iron depletion in the surroundings and growth arrest on cells located at the edge of a B. subtilis colony biofilm. In this study, we identified that pulcherrimin is primarily produced under biofilm conditions and provides protection to cells in the biofilm against oxidative stress. We presented molecular evidence on how pulcherrimin lowers the level of reactive oxygen species (ROS) and alleviates oxidative stress and DNA damage caused by ROS accumulation in a mature biofilm. We also performed global transcriptome profiling to identify differentially expressed genes in the pulcherrimin-deficient mutant compared with the wild type, and further characterized the regulation of genes by pulcherrimin that are related to iron homeostasis, DNA damage response (DDR), and oxidative stress response. Based on our findings, we propose pulcherrimin as an important antioxidant that modulates B. subtilis biofilm development., (© 2023. The Author(s).)

Physical interactions between proteins are essential for most biological processes governing life 1 . However, the molecular determinants of such interactions have been challenging to understand, even as genomic, proteomic and structural data increase. This knowledge gap has been a major obstacle for the comprehensive understanding of cellular protein-protein interaction networks and for the de novo design of protein binders that are crucial for synthetic biology and translational applications 2-9 . Here we use a geometric deep-learning framework operating on protein surfaces that generates fingerprints to describe geometric and chemical features that are critical to drive protein-protein interactions 10 . We hypothesized that these fingerprints capture the key aspects of molecular recognition that represent a new paradigm in the computational design of novel protein interactions. As a proof of principle, we computationally designed several de novo protein binders to engage four protein targets: SARS-CoV-2 spike, PD-1, PD-L1 and CTLA-4. Several designs were experimentally optimized, whereas others were generated purely in silico, reaching nanomolar affinity with structural and mutational characterization showing highly accurate predictions. Overall, our surface-centric approach captures the physical and chemical determinants of molecular recognition, enabling an approach for the de novo design of protein interactions and, more broadly, of artificial proteins with function., (© 2023. The Author(s).)

SARS-CoV-2 Omicron variant infection generally gives rise to asymptomatic to moderate COVID-19 in vaccinated people. The immune cells can be reprogrammed or "imprinted" by vaccination and infections to generate protective immunity against subsequent challenges. Considering the immune imprint in Omicron infection is unclear, here we delineate the innate immune landscape of human Omicron infection via single-cell RNA sequencing, surface proteome profiling, and plasma cytokine quantification. We found that monocyte responses predominated in immune imprints of Omicron convalescents, with IL-1β-associated and interferon (IFN)-responsive signatures with mild and moderate symptoms, respectively. Low-density neutrophils increased and exhibited IL-1β-associated and IFN-responsive signatures similarly. Mild convalescents had increased blood IL-1β, CCL4, IL-9 levels and PI3 + neutrophils, indicating a bias to IL-1β responsiveness, while moderate convalescents had increased blood CXCL10 and IFN-responsive monocytes, suggesting durative IFN responses. Therefore, IL-1β- or IFN-responsiveness of myeloid cells may indicate the disease severity of Omicron infection and mediate post-COVID conditions., (© 2022. The Author(s).)

We theoretically analyze the waveguiding structures photo-induced by two incoherent counter-propagating Bessel beams (BBs) in a biased photorefractive crystal. We demonstrate that the cross-coupling of two BBs enables adressable channels and tunability of the forming guiding structures. The truncation parameter of the BBs, their Bessel orders and the misalignment between the two beams are all key parameters for tailoring the characteristics of the photo-induced waveguides such as the number of outputs, the output intensity levels and the distance between each output channel. Accordingly, we optimized the different parameters for designing not only a fully tunable Y-coupler but also optical splitters with up to five outputs and even more complex star couplers for all-optical interconnect applications. Finally, we report on the stability behavior of the photo-induced platform. The stability threshold depends on the nonlinearity parameter beyond which the beams display time-periodic, quasi-periodic and turbulent dynamics where spatially localized instabilities can be observed. All these results suggest more opportunities for fully controllable complex waveguiding structures and new all-optical solutions for active components in optical telecommunication and innovative ways of performing optical computing based on spatiotemporal chaos., (© 2022. The Author(s).)

To obtain the presence of environmental contaminants in honeybee and compare the toxicity of the detected pesticides to Apis mellifera ligustica Spin and Apis cerana cerana Fabricius. In this work, 214 honeybee samples were collected to simultaneous monitoring 66 pesticides between 2016 and 2017 in China. A modified QuEChERS extraction method coupled with multi-residue analytical methods by Ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Gas chromatography-mass spectrum (GC-MS). Among, four pyrethroid pesticides were selected to test and compare the acute oral toxicities of two honeybees. And the survival risk of beta-cypermethrin was analyzed to them. Using this method, 21 compounds were detected, including 3 neonicotinoids, 5 pyrethroids, 5 organophosphorus and 8 others. Importantly, detected frequencies of pyrethroid pesticides were accounted for 53.3%. Among, acute toxicity values (LD 50 ) of four pyrethroid pesticides to the A.m. ligustica were higher than of that the A.c. cerana. When they were exposed to the same concentration of beta-cypermethrin (0.2906 mg/L), the survival rate of the A.m. ligustica (40.0%) was higher than the A.c. cerana (18.9%). Our work is valuable to analyze multiple pesticide residues of honeybees and evaluate the survival risk of two honeybee species, which also provides a basis for the risk assessment., (© 2022. The Author(s).)

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs.  1,2 ) (SARS-CoV-2), Middle East respiratory syndrome coronavirus 3 (MERS-CoV) and SARS-CoV-1 (ref.  4 ), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture 5-7 and in patient tissues 8-10 , suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage 1 . The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles 2 , epitope distribution 3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab 4 and cilgavimab 5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants., (© 2022. The Author(s).)

Plant-pathogenic fungi form intimate interactions with their associated bacterial microbiota during their entire life cycle. However, little is known about the structure, functions and interaction mechanisms of bacterial communities associated with fungal fruiting bodies (perithecia). Here we examined the bacterial microbiome of perithecia formed by Fusarium graminearum, the major pathogenic fungus causing Fusarium head blight in cereals. A total of 111 shared bacterial taxa were identified in the microbiome of 65 perithecium samples collected from 13 geographic locations. Within a representative culture collection, 113 isolates exhibited antagonistic activity against F. graminearum, with Pantoea agglomerans ZJU23 being the most efficient in reducing fungal growth and infectivity. Herbicolin A was identified as the key antifungal compound secreted by ZJU23. Genetic and chemical approaches led to the discovery of its biosynthetic gene cluster. Herbicolin A showed potent in vitro and in planta efficacy towards various fungal pathogens and fungicide-resistant isolates, and exerted a fungus-specific mode of action by directly binding and disrupting ergosterol-containing lipid rafts. Furthermore, herbicolin A exhibited substantially higher activity (between 5- and 141-fold higher) against the human opportunistic fungal pathogens Aspergillus fumigatus and Candida albicans in comparison with the clinically used fungicides amphotericin B and fluconazole. Its mode of action, which is distinct from that of other antifungal drugs, and its efficacy make herbicolin A a promising antifungal drug to combat devastating fungal pathogens, both in agricultural and clinical settings., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Absent epilepsy is a kind of refractory epilepsy, which is characterized by 2-4 Hz spike and wave discharges (SWDs) in electroencephalogram. Open-loop deep brain stimulation (DBS) targeting the thalamic reticular nucleus (TRN) is an effective method to treat absent epilepsy by eliminating SWDs in the brain. Compared with open-loop DBS, closed-loop DBS has been recognized by researchers for its advantages of significantly inhibiting seizures and having fewer side effects. Since traditional trial-and-error methods for adjusting closed-loop controller parameters are too dependent on the experience of doctors, in this paper we designed two proportional integral (PI) controllers based on the basal ganglia-cortical-thalamic model, whose PI parameters are calculated from the stability of the system. The two PI controllers can automatically adjust the frequency and amplitude of DBS respectively according to the change of the firing rate detected by substantia nigra pars reticulata (SNr). The parameters of the PI controller are calculated based on the Routh-Hurwitz stability criterion of a linear system which transformed by the original system using controlled auto-regressive (CAR) model and recursive least squares (RLS) method. Numerical simulation results show that both PI controllers significantly destroy the SWDs of the cerebral cortex and restore it to the other two normal discharge modes according to the different target firing rate, which supplies a promising brain stimulation strategy., (© 2022. The Author(s).)

Asymmetric positioning of the mitotic spindle contributes to the generation of two daughter cells with distinct sizes and fates. Here, we investigated an asymmetric division in the Caenorhabditis elegans Q neuroblast lineage. In this division, beginning with an asymmetrically positioned spindle, the daughter-cell size differences continuously increased during cytokinesis, and the smaller daughter cell in the posterior eventually underwent apoptosis. We found that Arp2/3-dependent F-actin assembled in the anterior but not posterior cortex during division, suggesting that asymmetric expansion forces generated by actin polymerization may enlarge the anterior daughter cell. Consistent with this, inhibition of cortical actin polymerization or artificially equalizing actin assembly led to symmetric cell division. Furthermore, disruption of the Wnt gradient or its downstream components impaired asymmetric cortical actin assembly and caused symmetric division. Our results show that Wnt signaling establishes daughter cell asymmetry by polarizing cortical actin polymerization in a dividing cell., (© 2022. The Author(s).)

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population 1 . Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies 2-10 , the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Mechanisms of the proliferation of liver are mainly studied in animal model of liver regeneration after partial hepatectomy (PH). However, the PH model involves complex regeneration mechanisms, including hemodynamic factors, cytokines, growth factors, and metabolites. Among liver metabolites, bile acid (BA) is a key signaling molecule that regulates liver regeneration. This study aimed to establish a new type of rapid liver hyperplasia model induced mainly by bile acid pathway through hepatoenteral circulation with hilar bile duct ligation (HBDL). We first established the HBDL model by ligating the bile duct of all hepatic lobes but the right lateral lobe in rabbits and compared with the PVL model and sham operation group. Changes in the liver lobe and hemodynamics were observed. Liver function and the bile acid level were also analyzed. Then we verified the HBDL model in mice. Liver function and the levels of bile acids and cytokines were tested. The protein and mRNA levels of FXR, FGF15, CYP7A1 and FoxM1b in liver tissue were also analyzed. After hilar ligation of the biliary tract, the unligated liver lobes proliferated significantly. Compared with those in the sham group, the volume and weight of the unligated right lateral lobe of the liver in the HBDL group and the PVL group increased significantly (P < 0.05). Transient liver function impairment occurred both in the HBDL group and PVL group in the rabbit model as well as the mouse models. The bile acid levels in the HBDL groups of the rabbit model and mouse model increased significantly within first week after surgery (P < 0.05). The immunohistochemistry results confirmed the proliferation of hepatocytes in the unligated liver lobe. Compared with those in the sham group, the levels of FXR, FGF15 and FoxM1b in the HBDL group were significantly increased (P < 0.05), while the expression of CYP7A1 was inhibited. Compared with those in the HBDL group, the postoperative hemodynamic changes in the PVL group were significant (P < 0.05). The levels of IL-6 and TNF-α in the HBDL group were higher than those in the sham group. The HBDL model is simple to establish and exhibits good surgical tolerance. The model has definite proliferative effect and strong specificity of bile acid pathway. This is an ideal animal model to study the mechanism of liver regeneration through bile acid pathway., (© 2021. The Author(s).)

It has been known that short-time auditory stimulation can contribute to the improvement of the balancing ability of the human body. The present study aims to explore the effects of white Gaussian noise (WGN) of different intensities and frequencies on dynamic balance performance in healthy young adults. A total of 20 healthy young participants were asked to stand at a dynamic balance force platform, which swung along the x-axis with an amplitude of ± 4° and frequency of 1 Hz. Their center of pressure (COP) trajectories were recorded when they were stimulated by WGN of different intensities (block 1) and different frequencies (block 2). A traditional method and detrended fluctuation analysis (DFA) were used for data preprocessing. The authors found that only with 75-85 dB WGN, the COP parameters improved. WGN frequency did not affect the dynamic balance performance of all the participants. The DFA results indicated stimulation with 75 dB WGN enhanced the short-term index and reduced the crossover point. Stimulation with 500 Hz and 2500 Hz WGN significantly enhanced the short-term index. These results suggest that 75 dB WGN and 500 Hz and 2500 Hz WGN improved the participants' dynamic balance performance. The results of this study indicate that a certain intensity of WGN is indispensable to achieve a remarkable improvement in dynamic balance. The DFA results suggest that WGN only affected the short-term persistence, indicating the potential of WGN being considered as an adjuvant therapy in low-speed rehabilitation training.

Alzheimer's disease (AD) is a common neurodegenerative disease with poor prognosis. New options for drug discovery targets are needed. We developed an imaging based arrayed CRISPR method to interrogate the human genome for modulation of in vitro correlates of AD features, and used this to assess 1525 human genes related to tau aggregation, autophagy and mitochondria. This work revealed (I) a network of tau aggregation modulators including the NF-κB pathway and inflammatory signaling, (II) a correlation between mitochondrial morphology, respiratory function and transcriptomics, (III) machine learning predicted novel roles of genes and pathways in autophagic processes and (IV) individual gene function inferences and interactions among biological processes via multi-feature clustering. These studies provide a platform to interrogate underexplored aspects of AD biology and offer several specific hypotheses for future drug discovery efforts.

This paper reports on the gas-phase amination reaction of aromatic hydrocarbons occurring under corona discharge conditions with N 2 gas as the nitrogen source. The corona discharge device within an atmospheric pressure chemical ionization source was employed to achieve the plasma-assisted N 2 fixation, and the coupled ion trap mass spectrometer (IT-MS) was used to detect positively charged product ions. In the model case, under APCI conditions, unusual product ions, [M + 16] + and [M + 14] + , were observed. Based on the high resolution MS data and tandem mass spectrometric information, [M + 16] + was confirmed to be protonated p-toluidine and [M + 14] + was confirmed to be p-methylphenylnitrenium ion. According to the experimental results of the isotopic labelling and substituent effect, one feasible mechanism is proposed as follows. Firstly, N 2 is activated by plasma caused via the corona discharge and then electrophilically attacks toluene, yielding the key intermediate, p-methylphenylnitrenium; secondly, the intermediate undergoes double-hydrogen transfer reaction to give rise to the final product ion, protonated p-toluidine. This study may provide a novel idea to explore new and green method for the synthesis of anilines.

Sleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal connectivity to multiple prefrontal and default mode network regions, and disrupted the relationships between memory performance and hippocampal connectivity. Following TSD, two nights of recovery sleep restored hippocampal connectivity to baseline levels, but did not fully restore memory performance nor its associations with hippocampal connectivity. These findings suggest that more than two nights of recovery sleep are needed to fully restore memory function and hippocampal-memory associations after one night of total sleep loss.

Cryptosporidium spp. and Enterocytozoon bieneusi are two well-known protist pathogens which can result in diarrhea in humans and animals. To examine the occurrence and genetic characteristics of Cryptosporidium spp. and E. bieneusi in pet red squirrels (Sciurus vulgaris), 314 fecal specimens were collected from red squirrels from four pet shops and owners in Sichuan province, China. Cryptosporidium spp. and E. bieneusi were examined by nested PCR targeting the partial small subunit rRNA (SSU rRNA) gene and the ribosomal internal transcribed spacer (ITS) gene respectively. The infection rates were 8.6% (27/314) for Cryptosporidium spp. and 19.4% (61/314) for E. bieneusi. Five Cryptosporidium species/genotypes were identified by DNA sequence analysis: Cryptosporidium rat genotype II (n = 8), Cryptosporidium ferret genotype (n = 8), Cryptosporidium chipmunk genotype III (n = 5), Cryptosporidium rat genotype I (n = 4), and Cryptosporidium parvum (n = 2). Additionally, a total of five E. bieneusi genotypes were revealed, including three known genotypes (D, SCC-2, and SCC-3) and two novel genotypes (RS01 and RS02). Phylogenetic analysis revealed that genotype D fell into group 1, whereas the remaining genotypes clustered into group 10. To our knowledge, this is the first study to report Cryptosporidium spp. and E. bieneusi in pet red squirrels in China. Moreover, C. parvum and genotype D of E. bieneusi, previously identified in humans, were also found in red squirrels, suggesting that red squirrels may give rise to cryptosporidiosis and microsporidiosis in humans through zoonotic transmissions. These results provide preliminary reference data for monitoring Cryptosporidium spp. and E. bieneusi infections in pet red squirrels and humans.

Head and neck lymphedema (HNL) is a disfiguring disease affecting over 90% of patients treated for head and neck cancer. Animal models of lymphedema are used to test pharmacologic and microsurgical therapies; however, no animal model for HNL is described in the literature to date. In this study we describe the first reproducible rat model for HNL. Animals were subjected to two surgical protocols: (1) lymphadenectomy plus irradiation; and (2) sham surgery and no irradiation. Head and neck expansion was measured on post-operative days 15, 30 and 60. Magnetic resonance imaging (MRI) was acquired at the same time points. Lymphatic drainage was measured at day 60 via indocyanine green (ICG) lymphography, after which animals were sacrificed for histological analysis. Postsurgical lymphedema was observed 100% of the time. Compared to sham-operated animals, lymphadenectomy animals experienced significantly more head and neck swelling at all timepoints (P < 0.01). Lymphadenectomy animals had significantly slower lymphatic drainage for 6 days post-ICG injection (P < 0.05). Histological analysis of lymphadenectomy animals revealed 83% greater subcutis thickness (P = 0.008), 22% greater collagen deposition (P = 0.001), 110% greater TGFβ1 + cell density (P = 0 . 04), 1.7-fold increase in TGFβ1 mRNA expression (P = 0.03), and 114% greater T-cell infiltration (P = 0.005) compared to sham-operated animals. In conclusion, animals subjected to complete lymph node dissection and irradiation developed changes consistent with human clinical postsurgical HNL. This was evidenced by significant increase in all head and neck measurements, slower lymphatic drainage, subcutaneous tissue expansion, increased fibrosis, and increased inflammation compared to sham-operated animals.

The graft-versus-leukemia effect reminds us to observe the allogeneic cell elicited anti-tumor immune responses. Here we immunized recipient B6 mice with different types of allogenic leukocytes and found that vaccination with allogenic dendritic cells (alloDC) elicited the most efficient protection against broad-spectrum tumors. The recipient lymphocytes were analyzed and the data showed that CD8 T cells increased significantly after immunization and expressed effector memory T cell marker KLRG1. Functional evaluation demonstrated that these KLRG1 + CD8 T cells could kill tumor cells in vitro and in vivo in Granzyme B- and Fas/FasL-dependent manners with no tumor antigen specificity, and tend to migrate into tumor sites by high expression of heparanase. Adoptive transfer of these cells could provide antitumor protection against tumors. AlloDC could also treat mice with residual tumors and combination of anti-PD1 antibody could enhance this effects. Together, our study showed that alloDC-immunization could induce potent antitumor effect through the expansion of KLRG1 + CD8 T cells, which can work as both preventive and therapeutic tumor vaccines.

Biliary tract infection (BTI)-derived sepsis remains a serious problem with significant morbidity and mortality in the modern era of critical care management. Current animal models of BTI have relied mostly on injecting purified bacteria or their toxins into the biliary tract. These models do not fully reflect pathophysiology or disease processes of clinical cholangitis or cholecystitis. In the current study, we developed a novel model of BTI by performing cholecystocolonic anastomosis (CCA) in rabbits and characterized pathophysiologic changes in this model. This model is intended to mimic the clinical process of cholecystocolonic fistula with reflux cholangitis, a severe form of BTI. Adult male rabbits were subjected to BTI-derived sepsis through an anastomosis of the gall bladder to the colon (i.e., CCA). The animals were monitored for 7 days to record survival. In additional groups of animals, various bacterial, hemodynamic, histological and biochemical parameters were measured at 12, 24, 48 and 72 h after CCA. The anastomosis between the gallbladder and the colon required about 5-8 min to finish. The median survival time for rabbits after CCA was 96 h. The positive rates of bacterial culture at 72 h after CCA were 83.3% and 100% in the blood and liver, respectively. The most common microorganism was Escherichia coli followed by Enterococcus. Plasma Tumor Necrosis Factor-α (TNF-α), Lnterleukin-10 (IL-10), Lnterleukin-6 (IL-6), and High-mobility group box 1 protein (HMGB-1) levels were greatly elevated after CCA. The cardiac index and heart rate increased slightly at 12 h after CCA and then continued to decrease. Systemic hypotension developed 48 h after CCA. Histological studies showed reflux cholangitis with acute lung and kidney injury. Cholecystocolonic anastomosis produces polymicrobial sepsis in rabbits, which mimics many aspects of human BTI-derived sepsis. It is reproducible and easy to perform and may serve as an excellent model for future sepsis research.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that causes substantial morbidity and mortality in livestock and humans. To date, there are no licensed human vaccines or therapeutics available. Here, we report the isolation of monoclonal antibodies from a convalescent patient, targeting the RVFV envelope proteins Gn and Gc. The Gn-specific monoclonal antibodies exhibited much higher neutralizing activities in vitro and protection efficacies in mice against RVFV infection, compared to the Gc-specific monoclonal antibodies. The Gn monoclonal antibodies were found to interfere with soluble Gn binding to cells and prevent infection by blocking the attachment of virions to host cells. Structural analysis of Gn complexed with four Gn-specific monoclonal antibodies resulted in the definition of three antigenic patches (A, B and C) on Gn domain I. Both patches A and B are major neutralizing epitopes. Our results highlight the potential of antibody-based therapeutics and provide a structure-based rationale for designing vaccines against RVFV.

Understanding the effects of climate variability and reservoir operation on runoff is important for shipping, irrigation and water supply services, especially during extreme drought years. After the operation of the Three Gorges Dam (TGD) began, the discharge processes in the mid-lower reaches of the Yangtze River were completely different from those during the pre-dam period. The measured hydrological data and the Mike 11-HD model were used to estimate the contributions of the TGD operation and climate variability to the variation in discharge during extreme drought years. The results are as follows: under the effects of the TGD operation and extreme drought, the special phenomenon of a "positive discharge anomaly in drought season and negative discharge anomaly in flood season" occurred compared with the conditions in the pre-dam period. During the flood season, the contributions of climate variation (TGD operation) to the changes in streamflow from Yichang station to Datong station were 86.6% (13.4%) and 80.7% (19.7%) in 2006 and 64.8% (35.2%) and 71.3% (28.7%) in 2011. During the dry season, the values were 81.2% (18.8%) and 93.9% (6.1%) in 2006 and 59.9% (40.1%) and 72.9% (27.1%) in 2011. Clearly, climate variation was the main reason for the variation in seasonal runoff. Furthermore, even in the 156 m and 175 m impoundments, climate variation was the dominant factor.

Yes-associated protein (YAP) has been identified as a key regulator of tissue homeostasis. However, the precise role and regulatory mechanism of YAP in esophageal squamous cell carcinoma (ESCC) remains unclear. Here we report that the genetic or pharmacological inhibition of YAP repressed cancer stem cell (CSC)-like properties, including tumorsphere-forming potential, cell motility, and chemoresistance in vitro, and was sufficient to attenuate tumor growth and CSC marker expression in ESCC xenografts. Mechanistically, YAP transcriptionally activated its downstream target SOX9 via TEAD1-mediated binding. We also observed a positive correlation between YAP signaling and SOX9 expression in two independent clinical cohorts. Intriguingly, YAP-targeting microRNAs, including miR-506-3p, which were induced by SOX9, post-transcriptionally repressed YAP expression, contributing to a negative feedback mechanism. Dual inhibition of YAP and SOX9 robustly suppressed malignant phenotypes. Notably, ESCC samples from The Cancer Genome Atlas (TCGA) dataset had frequent (44%) instances of YAP gene amplification and genetic inactivation of Hippo pathway regulators. Nuclear YAP expression was elevated in 197 ESCC tissues from a Chinese cohort. Together, our findings provide evidence that genetic hyperactivation of YAP unbalances the YAP-SOX9 feedback loop and confers CSC-like features in ESCC, suggesting that this YAP-SOX9 circuit represents a potential therapeutic target.

Gelatin-coupled cellulose (GCC) microgel with whisker-like structure is prepared and used to incorporate into casein (CA) matrix to construct reinforced CA-based composite films by solution casting. The GCC microgel has excellent dispersibility and stability in water, which contributes to the hydrophobicity and significantly reduces the moisture absorption of the composite films, as well as a decrease in the water vapor permeability with an increase of GCC content at different relative humidity is also observed. Compared with pure casein material, the resultant CA-based composite films show more homogeneous and dense cross-sectional structure, and the cleavage temperature of the hydrogen bonds increases by 16 °C. In particular, their tensile strength and Young's modulus increase by 6 and 3.5 times, respectively. These indicators are superior to that of the nanoparticle enhanced CA-based composite film. Moreover, the light transmittance of the CA-based films at 550 nm is about 88% when GCC content is higher than 9%. The above results could be attributed to the strong hydrogen bonds formed between GCC components and CA matrix, as further confirmed by fourier transform infrared spectra and X-ray diffraction analysis.

Viscum coloratum (Kom.) Nakai is one of active medicinal plants, and its active components, especially polysaccharides, have been shown to exhibit bioactivity. In this study, we examined the effects of three polysaccharide fractions from Viscum coloratum (Kom.) Nakai on HepG2 cell growth in a dose-dependent manner by using a CCK-8 assay kit. Flow cytometry analysis showed that VCP2 treatment delayed the cell cycle in the G1 phase and induced apoptosis in HepG2 cells, a result possibly due to the increased expression of p21 Wafl/Cip1 and Cyclin D and the decreased expression of Cyclin E and CDK4. The increased expression of Bad, Smac and Caspase-3 and the decreased expression of Bcl-XL and XIAP may be some of the reasons for the induction of apoptosis in VCP2-treated HepG2 cells. Through iTRAQ and 2D-LC-MSMS, 113 and 198 differentially expressed proteins were identified in normal and VCP2-treated HepG2 and Caco2 cells. The mRNA and protein levels of Histone H3.1, Cytoskeletal 9 and Vitronectin agreed with iTRAQ proteomic results. GO, pathways and the PPI of differentially expressed proteins were further analyzed. These findings broaden the understanding of the anti-tumor mechanisms of mistletoe polysaccharides and provide new clues for screening proteins that are responsive to polysaccharides.

Bacteriophages encode anti-CRISPR suppressors to counteract the CRISPR/Cas immunity of their bacterial hosts, thus facilitating their survival and replication. Previous studies have shown that two phage-encoded anti-CRISPR proteins, AcrF1 and AcrF2, suppress the type I-F CRISPR/Cas system of Pseudomonas aeruginosa by preventing target DNA recognition by the Csy surveillance complex, but the precise underlying mechanism was unknown. Here we present the structure of AcrF1/2 bound to the Csy complex determined by cryo-EM single-particle reconstruction. By structural analysis, we found that AcrF1 inhibits target DNA recognition of the Csy complex by interfering with base pairing between the DNA target strand and crRNA spacer. In addition, multiple copies of AcrF1 bind to the Csy complex with different modes when working individually or cooperating with AcrF2, which might exclude target DNA binding through different mechanisms. Together with previous reports, we provide a comprehensive working scenario for the two anti-CRISPR suppressors, AcrF1 and AcrF2, which silence CRISPR/Cas immunity by targeting the Csy surveillance complex.

Wound healing is significantly delayed in irradiated skin. To better understand global changes in protein expression after radiation, we utilized a reverse phase protein array (RPPA) to identify significant changes in paired samples of normal and irradiated human skin. Of the 210 proteins studied, fibronectin was the most significantly and consistently downregulated in radiation-damaged skin. Using a murine model, we confirmed that radiation leads to decreased fibronectin expression in the skin as well as delayed wound healing. Topically applied fibronectin was found to significantly improve wound healing in irradiated skin and was associated with decreased inflammatory infiltrate and increased angiogenesis. Fibronectin treatment may be a useful adjunctive modality in the treatment of non-healing radiation wounds.

Methods and mechanisms for improvement of photocatalytic activity, are important and popular research topics for renewable energy production and waste water treatment. Here, we demonstrate a facile laser drilling method for engineering well-aligned pore arrays on magnetron-sputtered WS 2 nanofilms with increased active edge sites; the proposed method promotes partial oxidation to fabricate WS 2 /WO 3 heterojunctions that enhance the separation of photogenerated electron-hole pairs. The WS 2 film after one, two, and three treatments exhibited photocurrent density of 3.9, 6.2, and 8 μA/cm 2 , respectively, reaching up to 31 times larger than that of pristine WS 2 film along with greatly improved charge recombination kinetics. The unprecedented combinational roles of laser drilling revealed in this study in regards to geometric tailoring, chemical transformation, and heterojunction positioning for WS 2- based composite nanomaterials create a foundation for further enhancing the performance of other 2D transition metal dichalcogenides in photocatalysis via laser treatment.

Bacteria switch between free-living and a multicellular state, known as biofilms, in response to cellular and environmental cues. It is important to understand how these cues influence biofilm development as biofilms are not only ubiquitous in nature but are also causative agents of infectious diseases. It is often believed that any stress triggers biofilm formation as a means of bacterial protection. In this study, we propose a new mechanism for how cellular and environmental DNA damage may influence biofilm formation. We demonstrate that Bacillus subtilis prevents biofilm formation and cell differentiation when stressed by oxidative DNA damage. We show that during B. subtilis biofilm development, a subpopulation of cells accumulates reactive oxygen species, which triggers the DNA damage response . Surprisingly, DNA damage response induction shuts off matrix genes whose products permit individual cells to stick together within a biofilm. We further revealed that DDR ON cells and matrix producers are mutually exclusive and spatially separated within the biofilm, and that a developmental checkpoint protein, Sda, mediates the exclusiveness. We believe this represents an alternative survival strategy, ultimately allowing cells to escape the multicellular community when in danger.

Silicon nitride stress capping layer is an industry proven technique for increasing electron mobility and drive currents in n-channel silicon MOSFETs. Herein, the strain induced by silicon nitride is firstly characterized through the changes in photoluminescence and Raman spectra of a bare bilayer MoS 2 (Molybdenum disulfide). To make an analogy of the strain-gated silicon MOSFET, strain is exerted to a bilayer MoS 2 field effect transistor (FET) through deposition of a silicon nitride stress liner that warps both the gate and the source-drain area. Helium plasma etched MoS 2 layers for edge contacts. Current on/off ratio and other performance metrics are measured and compared as the FETs evolve from back-gated, to top-gated and finally, to strain-gated configurations. While the indirect band gap of bilayer MoS 2 at 0% strain is 1.25 eV, the band gap decreases as the tensile strain increases on an average of ~100 meV per 1% tensile strain, and the decrease in band gap is mainly due to lowering the conduction band at K point. Comparing top- and strain-gated structures, we find a 58% increase in electron mobility and 46% increase in on-current magnitude, signalling a benign effect of tensile strain on the carrier transport properties of MoS 2 ., Competing Interests: The authors declare no competing financial interests.