Abstract
Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency and are associated with lower overall survival in breast cancer compared to single cells. Combining ...single-cell RNA sequencing and protein analyses, here we report the profiles of primary tumor cells and lung metastases of triple-negative breast cancer (TNBC). ICAM1 expression increases by 200-fold in the lung metastases of three TNBC patient-derived xenografts (PDXs). Depletion of ICAM1 abrogates lung colonization of TNBC cells by inhibiting homotypic tumor cell-tumor cell cluster formation. Machine learning-based algorithms and mutagenesis analyses identify ICAM1 regions responsible for homophilic ICAM1-ICAM1 interactions, thereby directing homotypic tumor cell clustering, as well as heterotypic tumor-endothelial adhesion for trans-endothelial migration. Moreover, ICAM1 promotes metastasis by activating cellular pathways related to cell cycle and stemness. Finally, blocking ICAM1 interactions significantly inhibits CTC cluster formation, tumor cell transendothelial migration, and lung metastasis. Therefore, ICAM1 can serve as a novel therapeutic target for metastasis initiation of TNBC.
Molecular electronics aims to miniaturize electronic devices by using subnanometre-scale active components. A single-molecule diode, a circuit element that directs current flow, was first proposed ...more than 40 years ago and consisted of an asymmetric molecule comprising a donor-bridge-acceptor architecture to mimic a semiconductor p-n junction. Several single-molecule diodes have since been realized in junctions featuring asymmetric molecular backbones, molecule-electrode linkers or electrode materials. Despite these advances, molecular diodes have had limited potential for applications due to their low conductance, low rectification ratios, extreme sensitivity to the junction structure and high operating voltages. Here, we demonstrate a powerful approach to induce current rectification in symmetric single-molecule junctions using two electrodes of the same metal, but breaking symmetry by exposing considerably different electrode areas to an ionic solution. This allows us to control the junction's electrostatic environment in an asymmetric fashion by simply changing the bias polarity. With this method, we reliably and reproducibly achieve rectification ratios in excess of 200 at voltages as low as 370 mV using a symmetric oligomer of thiophene-1,1-dioxide. By taking advantage of the changes in the junction environment induced by the presence of an ionic solution, this method provides a general route for tuning nonlinear nanoscale device phenomena, which could potentially be applied in systems beyond single-molecule junctions.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
Collagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte-associated immunoglobulin-like receptor (LAIR)-1. LAIR-2 is a ...secreted protein that can act as a decoy receptor by binding collagen with higher affinity than LAIR-1. We propose that collagens promote immune evasion by interacting with LAIR-1 expressed on immune cells, and that LAIR-2 releases LAIR-1-mediated immune suppression. Analysis of public human datasets shows that collagens, LAIR-1 and LAIR-2 have unique and overlapping associations with survival in certain tumors. We designed a dimeric LAIR-2 with a functional IgG1 Fc tail, NC410, and showed that NC410 increases human T cell expansion and effector function in vivo in a mouse xenogeneic-graft versus-host disease model. In humanized mouse tumor models, NC410 reduces tumor growth that is dependent on T cells. Immunohistochemical analysis of human tumors shows that NC410 binds to collagen-rich areas where LAIR-1
+
immune cells are localized. Our findings show that NC410 might be a novel strategy for cancer immunotherapy for immune-excluded tumors.
Aims
Aboveground plant litter inputs are important sources of soil carbon (C). We aimed to establish how experimentally altered litter inputs affect soil C to 1-m depth across different ecosystems, ...and over different timeframes.
Methods
We performed a meta-analysis of 237 studies across 248 sites worldwide to assess the influence of treatment magnitude, treatment duration, initial soil C content, and climate on the response of soil C to altered aboveground litter inputs.
Results
Overall, soil C content was lower under litter removal, but higher under litter addition compared to controls. The effects of litter manipulation were apparent throughout the soil profile and were related to treatment magnitude. Soil C content declined markedly with increasing duration of litter removal, whereas the positive effect of litter addition attenuated over time. Cropland management practices (bare fallow or additional straw incorporation) had similar effects on soil C to litter removal and addition treatments.
Conclusions
Our study reveals rapid and consistent changes in soil C content with altered litter inputs and provides important insights into plant residue management to enhance soil C sequestration. We highlight the need for long-term experiments, with a greater focus on the processes underpinning soil C storage in different ecosystems.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
When volcanic eruptions involve interaction with external water (hydrovolcanism), the result is an ash-rich and energetic volcanic plume, as illustrated dramatically by the January 2022 Tonga ...eruption. The origin of the high explosive energy of these events remains an important question. We investigate this question by studying Prince Rupert’s Drops (PRDs)—tadpole-shaped glass beads formed by dripping molten glass into water—which have long fascinated materials scientists because the great strength of the head contrasts with the explosivity of the metastable interior when the tail is broken. We show that the fragment size distribution (FSD) produced by explosive fragmentation changes systematically with PRD fragmentation in air, water, and syrup. Most FSDs are fractal over much of the size range, scaling that can be explained by the repeated fracture bifurcation observed in three-dimensional images from microcomputed tomography. The shapes of constituent fragments are determined by their position within the original PRD, with platey fragments formed from the outer (compressive) shell and blocky fragments formed by fractures perpendicular to interior voids. When molten drops fail to form PRDs, the glass disintegrates by quench granulation, a process that produces fractal FSDs but with a larger median size than explosively generated fragments. Critically, adding bubbles to the molten glass prevents PRD formation and promotes quench granulation, suggesting that granulation is modulated by heterogeneous stress fields formed around the bubbles during sudden cooling and contraction. Together, these observations provide insight into glass fragmentation and potentially, processes operating during hydrovolcanism.
Ecological and socioeconomic impacts from biological invasions are rapidly escalating worldwide. While effective management underpins impact mitigation, such actions are often delayed, insufficient ...or entirely absent. Presently, management delays emanate from a lack of monetary rationale to invest at early invasion stages, which precludes effective prevention and eradication. Here, we provide such rationale by developing a conceptual model to quantify the cost of inaction, i.e., the additional expenditure due to delayed management, under varying time delays and management efficiencies. Further, we apply the model to management and damage cost data from a relatively data-rich genus (
Aedes
mosquitoes). Our model demonstrates that rapid management interventions following invasion drastically minimise costs. We also identify key points in time that differentiate among scenarios of timely, delayed and severely delayed management intervention. Any management action during the severely delayed phase results in substantial losses
(
>
50
%
of the potential maximum loss). For
Aedes
spp., we estimate that the existing management delay of 55 years led to an additional total cost of approximately $ 4.57 billion (14% of the maximum cost), compared to a scenario with management action only seven years prior (< 1% of the maximum cost). Moreover, we estimate that in the absence of management action, long-term losses would have accumulated to US$ 32.31 billion, or more than seven times the observed inaction cost. These results highlight the need for more timely management of invasive alien species—either pre-invasion, or as soon as possible after detection—by demonstrating how early investments rapidly reduce long-term economic impacts.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Global warming has greatly altered winter snowfall patterns, and there is a trend towards increasing winter snow in semi‐arid regions in China. Winter snowfall is an important source of water during ...early spring in these water‐limited ecosystems, and it can also affect nutrient supply. However, we know little about how changes in winter snowfall will affect ecosystem productivity and plant community structure during the growing season. Here, we conducted a 5‐year winter snow manipulation experiment in a temperate grassland in Inner Mongolia. We measured ecosystem carbon flux from 2014 to 2018 and plant biomass and species composition from 2015 to 2018. We found that soil moisture increased under deepened winter snow in early growing season, particularly in deeper soil layers. Deepened snow increased the net ecosystem exchange of CO2 (NEE) and reduced intra‐ and inter‐annual variation in NEE. Deepened snow did not affect aboveground plant biomass (AGB) but significantly increased root biomass. This suggested that the enhanced NEE was allocated to the belowground, which improved water acquisition and thus contributed to greater stability in NEE in deep‐snow plots. Interestingly, the AGB of grasses in the control plots declined over time, resulting in a shift towards a forb‐dominated system. Similar declines in grass AGB were also observed at three other locations in the region over the same time frame and are attributed to 4 years of below‐average precipitation during the growing season. By contrast, grass AGB was stabilized under deepened winter snow and plant community composition remained unchanged. Hence, our study demonstrates that increased winter snowfall may stabilize arid grassland systems by reducing resource competition, promoting coexistence between plant functional groups, which ultimately mitigates the impacts of chronic drought during the growing season.
Winter snowfall is a critical water source for plant growth during early spring, especially in water‐limited grasslands. However, we know little about how changes in winter snowfall will affect ecosystem productivity and plant community structure during the growing season. Our 5‐year snow manipulation experiment showed that deepened snow enhanced net ecosystem CO2 exchange and resulted in greater belowground biomass allocation by increasing growing season water availability, especially in deep soils. Consequently, deep snow maintained the coexistence of plant functional groups (grasses and forbs), and stabilized plant community composition and productivity under a changing environment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Surgical site infection (SSI) rates vary from 1% to 5% in the month following surgery. Due to the large number of surgical procedures conducted annually, the costs of these SSIs can be ...considerable in financial and social terms. Many interventions are used with the aim of reducing the risk of SSI in people undergoing surgery. These interventions can be broadly delivered at three stages: preoperatively, intraoperatively and postoperatively. The intraoperative interventions are largely focused on decontamination of skin using soap and antiseptics; the use of barriers to prevent movement of micro‐organisms into incisions; and optimising the patient's own bodily functions to promote best recovery. Both decontamination and barrier methods can be aimed at people undergoing surgery and operating staff. Other interventions focused on SSI prevention may be aimed at the surgical environment and include methods of theatre cleansing and approaches to managing theatre traffic.
Objectives
To present an overview of Cochrane Reviews of the effectiveness and safety of interventions, delivered during the intraoperative period, aimed at preventing SSIs in all populations undergoing surgery in an operating theatre.
Methods
Published Cochrane systematic reviews reporting the effectiveness of interventions delivered during the intraoperative period in terms of SSI prevention were eligible for inclusion in this overview. We also identified Cochrane protocols and title registrations for future inclusion into the overview. We searched the Cochrane Library on 01 July 2017. Two review authors independently screened search results and undertook data extraction and 'Risk of bias' and certainty assessment. We used the ROBIS (risk of bias in systematic reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the certainty of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables.
Main results
We included 32 Cochrane Reviews in this overview: we judged 30 reviews as being at low risk of bias and two at unclear risk of bias. Thirteen reviews had not been updated in the past three years. Two reviews had no relevant data to extract. We extracted data from 30 reviews with 349 included trials, totaling 73,053 participants. Interventions assessed included gloving, use of disposable face masks, patient oxygenation protocols, use of skin antiseptics for hand washing and patient skin preparation, vaginal preparation, microbial sealants, methods of surgical incision, antibiotic prophylaxis and methods of skin closure. Overall, the GRADE certainty of evidence for outcomes was low or very low. Of the 77 comparisons providing evidence for the outcome of SSI, seven provided high‐ or moderate‐certainty evidence, 39 provided low‐certainty evidence and 31 very low‐certainty evidence. Of the nine comparisons that provided evidence for the outcome of mortality, five provided low‐certainty evidence and four very low‐certainty evidence.
There is high‐ or moderate‐certainty evidence for the following outcomes for these intraoperative interventions. (1) Prophylactic intravenous antibiotics administered before caesarean incision reduce SSI risk compared with administration after cord clamping (10 trials, 5041 participants; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.44 to 0.81; high‐certainty evidence ‐ assessed by review authors). (2) Preoperative antibiotics reduce SSI risk compared with placebo after breast cancer surgery (6 trials, 1708 participants; RR 0.74, 95% CI 0.56 to 0.98; high‐certainty evidence ‐ assessed by overview authors). (3) Antibiotic prophylaxis probably reduce SSI risk in caesarean sections compared with no antibiotics (82 relevant trials, 14,407 participants; RR 0.40, 95% CI 0.35 to 0.46; moderate‐certainty evidence; downgraded once for risk of bias ‐ assessed by review authors). (4) Antibiotic prophylaxis probably reduces SSI risk for hernia repair compared with placebo or no treatment (17 trials, 7843 participants; RR 0.67, 95% CI 0.54 to 0.84; moderate‐certainty evidence; downgraded once for risk of bias ‐ assessed by overview authors); (5) There is currently no clear difference in the risk of SSI between iodine‐impregnated adhesive drapes compared with no adhesive drapes (2 trials, 1113 participants; RR 1.03, 95% CI 0.66 to 1.60; moderate‐certainty evidence; downgraded once for imprecision ‐ assessed by review authors); (6) There is currently no clear difference in SSI risk between short‐term compared with long‐term duration antibiotics in colorectal surgery (7 trials; 1484 participants; RR 1.05 95% CI 0.78 to 1.40; moderate‐certainty evidence; downgraded once for imprecision ‐ assessed by overview authors). There was only one comparison showing negative effects associated with the intervention: adhesive drapes increase the risk of SSI compared with no drapes (5 trials; 3082 participants; RR 1.23, 95% CI 1.02 to 1.48; high‐certainty evidence ‐ rated by review authors).
Authors' conclusions
This overview provides the most up‐to‐date evidence on use of intraoperative treatments for the prevention of SSIs from all currently published Cochrane Reviews. There is evidence that some interventions are useful in reducing SSI risk for people undergoing surgery, such as antibiotic prophylaxis for caesarean section and hernia repair, and also the timing of prophylactic intravenous antibiotics administered before caesarean incision. Also, there is evidence that adhesive drapes increase SSI risk. Evidence for the many other treatment choices is largely of low or very low certainty and no quality‐of‐life or cost‐effectiveness data were reported. Future trials should elucidate the relative effects of some treatments. These studies should focus on increasing participant numbers, using robust methodology and being of sufficient duration to adequately assess SSI. Assessment of other outcomes such as mortality might also be investigated as part of non‐experimental prospective follow‐up of people with SSI of different severity, so the risk of death for different subgroups can be better understood.
Volcanic gas emissions are intimately linked to the dynamics of magma ascent and outgassing and, on geological time scales, constitute an important source of volatiles to the Earth's atmosphere. ...Measurements of gas composition and flux are therefore critical to both volcano monitoring and to determining the contribution of volcanoes to global geochemical cycles. However, significant gaps remain in our global inventories of volcanic emissions, (particularly for CO2, which requires proximal sampling of a concentrated plume) for those volcanoes where the near‐vent region is hazardous or inaccessible. Unmanned Aerial Systems (UAS) provide a robust and effective solution to proximal sampling of dense volcanic plumes in extreme volcanic environments. Here we present gas compositional data acquired using a gas sensor payload aboard a UAS flown at Volcán Villarrica, Chile. We compare UAS‐derived gas time series to simultaneous crater rim multi‐GAS data and UV camera imagery to investigate early plume evolution. SO2 concentrations measured in the young proximal plume exhibit periodic variations that are well correlated with the concentrations of other species. By combining molar gas ratios (CO2/SO2 = 1.48–1.68, H2O/SO2 = 67–75, and H2O/CO2 = 45–51) with the SO2 flux (142 ± 17 t/day) from UV camera images, we derive CO2 and H2O fluxes of ~150 t/day and ~2,850 t/day, respectively. We observe good agreement between time‐averaged molar gas ratios obtained from simultaneous UAS‐ and ground‐based multi‐GAS acquisitions. However, the UAS measurements made in the young, less diluted plume reveal additional short‐term periodic structure that reflects active degassing through discrete, audible gas exhalations.
Key Points
We present high‐resolution gas compositional data acquired using a multirotor Unmanned Aerial System (UAS) at Volcán Villarrica, Chile
We derive SO2, CO2, and H2O fluxes of ~162, ~150, and ~2850 t/day, respectively
UAS gas measurements made in the young, undiluted plume reveal short‐term periodic active degassing associated with audible gas exhalations
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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