Assessing the Prognostic Utility of the New Mayo Adhesive Probability Score in East Asian Populations and its Correlation with Metabolic-Associated Fatty Liver Disease.

We assessed the prognostic utility of the new perinephric fat adherence risk score - Mayo Adhesive Probability (MAP), in patients of East Asian ethnicity undergoing either laparoscopic partial nephrectomy (LPN) or laparoscopic radical nephrectomy (LRN). A retrospective analysis of clinical data was carried out on 169 patients who either underwent LPN or LRN surgery. These patients were categorized into two groups, group A (0-2 points) and group B (3-4 points) using the new MAP score. The overall clinical data between these two groups was compared and potential risk factors were investigated using logistic regression analyses. The new MAP score yielded an area under the curve of 0.761 (95 % CI: 0.691-0.831), indicating its effectiveness. Group B had a significantly higher incidence of adherent perirenal fat (APF) during surgery (p<0.001) and had a greater average age (p<0.001). There was an increased prevalence of hypertension (p=0.009), type 2 diabetes mellitus (p<0.001), and MAFLD (p<0.001) in group B. Additionally, there were significant differences in posterior perinephric fat thickness (p<0.05), lateral perinephric fat thickness (p<0.001), and perinephric stranding (p<0.001) between the two groups. The new MAP score holds significance in predicting APF in people of East Asian ethnicity undergoing LPN or LRN, and there is a strong correlation between elevated MAP scores and risk factors such as MAFLD and advanced age.

Microplastics and Nanoplastics Impair the Biophysical Function of Pulmonary Surfactant by Forming Heteroaggregates at the Alveolar-Capillary Interface.

Microplastics (MPs) are ubiquitous environmental pollutants produced through the degradation of plastic products. Nanoplastics (NPs), commonly coexisting with MPs in the environment, are submicrometer debris incidentally produced from fragmentation of MPs. We studied the biophysical impacts of MPs/NPs derived from commonly used commercial plastic products on a natural pulmonary surfactant extracted from calf lung lavage. It was found that in comparison to MPs/NPs derived from lunch boxes made of polypropylene or from drinking water bottles made of poly(ethylene terephthalate), the MP/NP derived from foam packaging boxes made of polystyrene showed the highest adverse impact on the biophysical function of the pulmonary surfactant. Accordingly, intranasal exposure of MP/NP derived from the foam boxes also induced the most serious proinflammatory responses and lung injury in mice. Atomic force microscopy revealed that NP particles were adsorbed on the air-water surface and heteroaggregated with the pulmonary surfactant film. These results indicate that although the incidentally formed NPs only make up a small mass fraction, they likely play a predominant role in determining the nano-bio interactions and the lung toxicity of MPs/NPs by forming heteroaggregates at the alveolar-capillary interface. These findings may provide novel insights into understanding the health impact of MPs and NPs on the respiratory system.

HRS mediates tumor immune evasion by regulating proteostasis-associated interferon pathway activation.

By sorting receptor tyrosine kinases into endolysosomes, the endosomal sorting complexes required for transport (ESCRTs) are thought to attenuate oncogenic signaling in tumor cells. Paradoxically, ESCRT members are upregulated in tumors. Here, we show that disruption of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), a pivotal ESCRT component, inhibited tumor growth by promoting CD8+ T cell infiltration in melanoma and colon cancer mouse models. HRS ablation led to misfolded protein accumulation and triggered endoplasmic reticulum (ER) stress, resulting in the activation of the type I interferon pathway in an inositol-requiring enzyme-1α (IRE1α)/X-box binding protein 1 (XBP1)-dependent manner. HRS was upregulated in tumor cells with high tumor mutational burden (TMB). HRS expression associates with the response to PD-L1/PD-1 blockade therapy in melanoma patients with high TMB tumors. HRS ablation sensitized anti-PD-1 treatment in mouse melanoma models. Our study shows a mechanism by which tumor cells with high TMB evade immune surveillance and suggests HRS as a promising target to improve immunotherapy.

Adverse Biophysical Impact of e-Cigarette Flavors on Pulmonary Surfactant.

The attractiveness and abundance of flavors are primary factors eliciting youth to use e-cigarettes. Emerging studies in recent years revealed the adverse health impact of e-cigarette flavoring chemicals, including disruption of the biophysical function of pulmonary surfactants in the lung. Nevertheless, a comprehensive understanding of the biophysical impact of various flavoring chemicals is still lacking. We used constrained drop surfactometry as a new alternative method to study the biophysical impact of flavored e-cigarette aerosols on an animal-derived natural pulmonary surfactant. The dose of exposure to e-cigarette aerosols was quantified with a quartz crystal microbalance, and alterations to the ultrastructure of the surfactant film were visualized using atomic force microscopy. We have systematically studied eight representative flavoring chemicals (benzyl alcohol, menthol, maltol, ethyl maltol, vanillin, ethyl vanillin, ethyl acetate, and ethyl butyrate) and six popular recombinant flavors (coffee, vanilla, tobacco, cotton candy, menthol/mint, and chocolate). Our results suggested a flavor-dependent inhibitory effect of e-cigarette aerosols on the biophysical properties of the pulmonary surfactant. A qualitative phase diagram was proposed to predict the hazardous potential of various flavoring chemicals. These results provide novel implications in understanding the environmental, health, and safety impacts of e-cigarette aerosols and may contribute to better regulation of e-cigarette products.

A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles.

Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.

Langmuir-Blodgett transfer from the oil-water interface.

HYPOTHESIS: Almost all Langmuir-Blodgett (LB) films were prepared with the classical Langmuir film balance, developed more than a century ago. To date, the success of the classical Langmuir film balance and the LB transfer technique is primarily restricted to the study of self-assembled monolayers at the air-water surface. It is challenging to study self-assembled monolayers at the oil-water interface, since the Langmuir film balance requires stacked oil and water layers. We hypothesize that a newly developed experimental method, called constrained drop surfactometry (CDS), is capable of preparing and characterizing LB films from the oil-water interface. EXPERIMENTS: We have developed a novel droplet-based LB transfer technique capable of preparing LB films from the oil-water interface. In conjunction with atomic force microscopy, we have demonstrated the capacity of the CDS in studying a natural pulmonary surfactant film self-assembled at the perfluorocarbon-water interface, and have compared to the LB films prepared from the air-water surface using the classical Langmuir film balance. FINDINGS: Our findings have demonstrated a novel paradigm for studying self-assembled monolayers and for preparing LB films from the oil-water interface. The CDS holds great promise for expanding the applicability of the traditional LB transfer technique from the air-water surface to the oil-water interface.

[Application of robot-assisted laparoscopic sentinel lymph node tracing in treating endometrial carcinoma].

Objective: To investigate the value of robot-assisted laparoscopic indocyanine green sentinel lymph node (SLN) tracing in treating endometrial carcinoma. Methods: Thirty-two patients with early-staging endometrial carcinoma were operated with laparoscopic comprehensive staging laparotomy from January 2019 to December 2021. At the same time, the SLN detection was performed by near-infrared fluorescence imaging tracer technology, in which the tracer was indocyanine green. Sixteen cases were injected with indocyanine green before laparoscopic surgery, and 16 cases were injected with indocyanine green before robot-assisted laparoscopic surgery. The operation index, postoperative complications, prognosis, and lymph node dissection were compared between the two groups. Results: (1) The mean age of patients in the robot group was (54.7±8.1) years old, and was (54.9±8.8) years old in the laparoscopic group. There were no significant difference between the two groups (t=0.06, P=0.951). (2) Intraoperative blood loss [(131±40) vs (169±57) ml], hemoglobin difference before and after surgery [(11.2±5.4) vs (15.5±5.7) g/L], the length of stay after operation [(6.2±1.3) vs (8.6±1.4) days] between the robot group and the laparoscopic group were compared, and the differences were statistically significant (all P<0.05). (3) SLNs were detected in all 16 patients in the robotic group, and a total of 41 SLNs were detected. SLNs were detected in 15 of the 16 patients in the laparoscopy group, and a total of 40 SLNs were detected. Compared with the laparoscopic group (15/16), the total detection rate of SLN in the robotic group (16/16), there were no statistical significance (χ2=1.03, P=0.310). Compared with the laparoscopic group (7/15), the SLN bilateral detection rate in the robotic group (10/16), there were also no significant difference (χ2=0.78, P=0.376). The number of lymph nodes detected in surgery group (16.6±4.1) were lower than those in the laparoscopy surgery group (21.0±7.1), while there were no statistically difference between the two groups (χ2=2.01, P=0.054). There was no tumor metastasis in the resected lymph nodes and SLN between the two groups. The false negative rate of SLN in diagnosing endometrial cancer postoperative lymph node metastasis was 0, and the negative predictive value was 100%. (4) The pelvic and retroperitoneal lymph nodes were divided into five regions, which were the left pelvis, the right pelvis, the presacral region, the deep inguinal region, and the abdominal aorta. The numbers of SLN of unilateral detection and bilateral pelvic detection between two groups showed no significant differences (all P>0.05). The left pelvis had the most SLN imaging in both groups, followed by the right pelvis, para-aortic, and deep groin. (5) There was one patient in both robotic group and laparoscopic group with postoperative complications, which were urinary retention and pelvic lymph node cyst respectively. There were no significant differences in the incidence of complications between the two groups (χ2=0.97, P=1.000). The median follow-up time after operation was 14 months (range 6-24 months). During the follow-up period, no local recurrence or distant metastasis was found between the two groups of endometrial cancer patients. Conclusions: Compared with the laparoscopic group, the robot group has less intraoperative blood loss and shorter postoperative hospital stay. The bilateral detection rate of SLN in the group was better than that of laparoscopy.

E-cigarette aerosol exposure of pulmonary surfactant impairs its surface tension reducing function.

INTRODUCTION: E-cigarette (EC) and vaping use continue to remain popular amongst teenage and young adult populations, despite several reports of vaping associated lung injury. One of the first compounds that EC aerosols comes into contact within the lungs during a deep inhalation is pulmonary surfactant. Impairment of surfactant's critical surface tension reducing activity can contribute to lung dysfunction. Currently, information on how EC aerosols impacts pulmonary surfactant remains limited. We hypothesized that exposure to EC aerosol impairs the surface tension reducing ability of surfactant. METHODS: Bovine Lipid Extract Surfactant (BLES) was used as a model surfactant in a direct exposure syringe system. BLES (2ml) was placed in a syringe (30ml) attached to an EC. The generated aerosol was drawn into the syringe and then expelled, repeated 30 times. Biophysical analysis after exposure was completed using a constrained drop surfactometer (CDS). RESULTS: Minimum surface tensions increased significantly after exposure to the EC aerosol across 20 compression/expansion cycles. Mixing of non-aerosolized e-liquid did not result in significant changes. Variation in device used, addition of nicotine, or temperature of the aerosol had no additional effect. Two e-liquid flavours, menthol and red wedding, had further detrimental effects, resulting in significantly higher surface tension than the vehicle exposed BLES. Menthol exposed BLES has the highest minimum surface tensions across all 20 compression/expansion cycles. Alteration of surfactant properties through interaction with the produced aerosol was observed with a basic e-liquid vehicle, however additional compounds produced by added flavourings appeared to be able to increase inhibition. CONCLUSION: EC aerosols alter surfactant function through increases in minimum surface tension. This impairment may contribute to lung dysfunction and susceptibility to further injury.

[Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro].

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHODS: The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULTS: Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 µg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 µg/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 µmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 µmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro. CONCLUSION: Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules.

Acyl-CoA thioesterase 9 promotes tumour growth and metastasis through reprogramming of fatty acid metabolism in hepatocellular carcinoma.

Acyl-CoA thioesterase 9 (ACOT9) is a critical regulator of cellular utilization of fatty acids by catalysing the hydrolysis of acyl-CoA thioesters to non-esterified fatty acid and coenzyme A (CoA). Recently, ACOT9 was reported to participate in the pathogenesis of non-alcoholic liver disease (NAFLD), which arises from aberrant lipid metabolism and serves as a risk factor for hepatocellular carcinoma (HCC). However, the functions of ACOT9 in carcinogenesis and aberrant lipid metabolism in HCC remain unexplored. Here, we found that ACOT9 expression is significantly elevated in HCC at least partially due to the down-regulation of miR-449c-3p. Upregulation of ACOT9 is closely associated with poor prognosis for patients with HCC. Knockdown of ACOT9 expression in HCC cells significantly decreased cell proliferation, colony formation, migration and invasion, mainly through suppression of G1-to-S cell cycle transition and epithelial-to-mesenchymal transition (EMT). By contrast, forced ACOT9 expression promoted HCC growth and metastasis. In addition, we found that ACOT9 reprogrammed lipid metabolism in HCC cells by increasing de novo lipogenesis. Furthermore, we demonstrated that increased lipogenesis was involved in ACOT9-promoted HCC growth and metastasis. Altogether, we demonstrate that ACOT9 plays a critical oncogenic role in the promotion of tumour growth and metastasis by reprogramming lipid metabolism in HCC, indicating ACOT9 as a potential therapeutic target in treatment of HCC.

S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers.

Pulmonary surfactant has been attempted as a supportive therapy to treat COVID-19. Although it is mechanistically accepted that the fusion peptide in the S2 subunit of the S protein plays a predominant role in mediating viral fusion with the host cell membrane, it is still unknown how the S2 subunit interacts with the natural surfactant film. Using combined bio-physicochemical assays and atomic force microscopy imaging, it was found that the S2 subunit inhibited the biophysical properties of the surfactant and induced microdomain fusion in the surfactant monolayer. The surfactant inhibition has been attributed to membrane fluidization caused by insertion of the S2 subunit mediated by its fusion peptide. These findings may provide novel insight into the understanding of bio-physicochemical mechanisms responsible for surfactant interactions with SARS-CoV-2 and may have translational implications in the further development of surfactant replacement therapy for COVID-19 patients.

Self-assembled aluminum oxyhydroxide nanorices with superior suspension stability for vaccine adjuvant.

The suspension stability of aluminum-based adjuvant (Alum) plays an important role in determining the Alum-antigen interaction and vaccine efficacy. Inclusion of excipients has been shown to stabilize antigens in vaccine formulations. However, there is no mechanistic study to tune the characteristics of Alum for improved suspension stability. Herein, a library of self-assembled rice-shaped aluminum oxyhydroxide nanoadjuvants i.e., nanorices (NRs), was synthesized through intrinsically controlled crystallization and atomic coupling-mediated aggregations. The NRs exhibited superior suspension stability in both water and a saline buffer. After adsorbing hepatitis B surface antigen (HBsAg) virus-like particles (VLPs), human papillomavirus virus (HPV) VLPs, or bovine serum albumin, NR-antigen complexes exhibited less sedimentation. Further mechanistic study demonstrated that the improved suspension stability was due to intraparticle aggregations that led to the reduction of the surface free energy. By using HBsAg in a murine vaccination model, NRs with higher aspect ratios elicited more potent humoral immune responses. Our study demonstrated that engineered control of particle aggregation provides a novel material design strategy to improve suspension stability for a diversity of biomedical applications.

Menthol in electronic cigarettes causes biophysical inhibition of pulmonary surfactant.

With an increasing prevalence of electronic cigarette (e-cigarette) use, especially among youth, there is an urgent need to better understand the biological risks and pathophysiology of health conditions related to e-cigarettes. A majority of e-cigarette aerosols are in the submicron size and would deposit in the alveolar region of the lung, where they must first interact with the endogenous pulmonary surfactant. To date, little is known whether e-cigarette aerosols have an adverse impact on the pulmonary surfactant. We have systematically studied the effect of individual e-cigarette ingredients on an animal-derived clinical surfactant preparation, bovine lipid extract surfactant, using a combination of biophysical and analytical techniques, including in vitro biophysical simulations using constrained drop surfactometry, molecular imaging with atomic force microscopy, chemical assays using carbon nuclear magnetic resonance and circular dichroism, and in silico molecular dynamics simulations. All data collectively suggest that flavorings used in e-cigarettes, especially menthol, play a predominant role in inhibiting the biophysical function of the surfactant. The mechanism of biophysical inhibition appears to involve menthol interactions with both phospholipids and hydrophobic proteins of the natural surfactant. These results provide novel insights into the understanding of the health impact of e-cigarettes and may contribute to better regulation of e-cigarette products.

RGD-modified dextran hydrogel promotes follicle growth in three-dimensional ovarian tissue culture in mice.

In vitro follicle growth is a promising technology to preserve fertility for cancer patients. We previously developed a three-dimensional (3-D) ovarian tissue culture system supported by mouse tumor cell-derived Matrigel. When murine ovarian tissues at 14 days old were cultured in Matrigel drops, antrum formation and oocyte competence were significantly enhanced compared with those cultured without Matrigel. In this study, we tested whether nonanimal-derived dextran hydrogels can support a 3-D ovarian tissue culture. We employed chemically defined dextran hydrogels consisting of dextran polymers crosslinked with polyethylene glycol (PEG)-based cell-degradable crosslinker. To determine the optimal gel elasticity for the 3-D tissue culture, we measured Young's modulus of dextran hydrogels at four concentrations (1.75, 2.25, 2.75, and 3.25 mmol/L), and cultured ovarian tissues in these gels for 7 days. As a result, 2.25 mmol/L dextran hydrogel with Young's modulus of 224 Pa was appropriate to provide physical support as well as to promote follicle expansion in the 3-D system. To mimic the natural extracellular matrix (ECM) environment, we modified the dextran hydrogels with two bioactive factors: ECM-derived Arg-Gly-Asp (RGD) peptides as a cell-adhesive factor, and activin A. The ovarian tissues were cultured in 2.25 mmol/L dextran hydrogels under four different conditions: Activin-/RGD- (A-R-), A + R-, A-R+, and A + R+. On Day 7 of culture, follicle and oocyte sizes were significantly increased in the RGD-modified conditions compared with those without RGD. The RGD-modified hydrogels also promoted mRNA levels of steroidogenic-related genes and estradiol production in the 3-D ovarian tissue culture. In vitro maturation and developmental competence of follicular oocytes were remarkably improved in the presence of RGD. In particular, blastocyst embryos were obtained only from A-R+ or A+R+ conditions after in vitro fertilization. We also determined synergistic effects of the RGD peptides and activin A on follicle growth and oocyte development in the 3-D tissue culture. In conclusion, our results suggest that RGD-modified dextran hydrogels provide an ECM-mimetic bioactive environment to support folliculogenesis in a 3-D ovarian tissue culture system.

Quantitative Determination of the Hydrophobicity of Nanoparticles.

The hydrophobicity of nanoparticles (NPs) is one of the most important physicochemical properties that determines their agglomeration state under various environmental conditions. When studying nano-bio interactions, it is found that the hydrophobicity of NPs plays a predominant role in mediating the biological response and toxicity of the NPs. Although many methods have been developed to qualitatively or quantitatively determine hydrophobicity, there is not yet a scientific consensus on the standard of characterizing the hydrophobicity of NPs. We have developed a novel optical method, called the maximum particle dispersion (MPD), for quantitatively characterizing the hydrophobicity of NPs. The principle of measurement of the MPD method lies in the control of the aggregation state of the NPs via manipulating the van der Waals interactions between NPs across a dispersion liquid. We have scrutinized the mechanism of the MPD method using a combination of dynamic light scattering and atomic force microscopy and further verified the MPD method using a completely independent dye adsorption method. The MPD method demonstrated great promise to be developed into an easy-to-use and cost-effective method for quantitatively characterizing the hydrophobicity of NPs.

CXCL12/CXCR4 Mediates Orthodontic Root Resorption via Regulating the M1/M2 Ratio.

Mechanical force-induced external root resorption is a major clinical side effect of orthodontic treatment. Recent work has revealed that M1 macrophages play a vital role in promoting orthodontic root resorption (ORR), but the mechanism of how mechanical force stimulation increases the M1/M2 macrophage ratio in periodontal tissue is poorly understood. In the current study, we showed that C-X-C motif chemokine 12 (CXCL12)+ periodontal ligament cells (PDLCs) and C-X-C chemokine receptor type 4 (CXCR4)+ monocytes in the periodontal ligament (PDL) were significantly increased after force application with ongoing root resorption, and these effects were partially rescued after force removal in mice. The expression of CXCL12 in PDLCs was increased by force stimulation in a time- and intensity-dependent manner in vitro. Blockage of the CXCL12/CXCR4 axis using CXCR4 antagonist AMD3100 was sufficient to alleviate ORR and reverse the force-enhanced M1/M2 macrophage ratio. Further mechanism exploration showed that Ly6Chi inflammatory monocytes homed in a CXCL12/CXCR4 axis-dependent manner. The number and proportion of CD11b+ Ly6Chi inflammatory monocytes in cervical lymph nodes were significantly increased by force loading, accompanied by decreased CD11b+ Ly6Chi monocytes in the blood. These changes were blunted by intraperitoneal injection of AMD3100. In addition, blockage of the CXCL12/CXCR4 axis effectively reversed M2 suppression and promoted M1 polarization. Collectively, results indicate that force-induced CXCL12/CXCR4 axis mediates ORR by increasing the M1/M2 ratio in periodontal tissues through attracting Ly6Chi inflammatory monocytes and modulating macrophage polarization. The results also imply that AMD3100 is potentially inhibitory to root resorption.

Alveolar Bone Marrow Gli1+ Stem Cells Support Implant Osseointegration.

Osseointegration is the key issue for implant success. The in vivo properties of cell populations driving the osseointegration process have remained largely unknown. In the current study, using tissue clearing-based 3-dimensional imaging and transgenic mouse model-based lineage tracing methods, we identified Gli1+ cells within alveolar bone marrow and their progeny as the cell population participating in extraction socket healing and implant osseointegration. These Gli1+ cells are surrounding blood vessels and do not express lineage differentiation markers. After tooth extraction and delayed placement of a dental implant, Gli1+ cells were activated into proliferation, and their descendants contributed significantly to new bone formation. Ablation of Gli1+ cells severely compromised the healing and osseointegration processes. Blockage of canonical Wnt signaling resulted in impaired recruitment of Gli1+ cells and compromised bone healing surrounding implants. Collectively, these findings demonstrate that Gli1+ cells surrounding alveolar bone marrow vasculature are stem cells supporting dental implant osseointegration. Canonical Wnt signal plays critical roles in regulating Gli1+ stem cells.

Binding of Benzo[a]pyrene Alters the Bioreactivity of Fine Biochar Particles toward Macrophages Leading to Deregulated Macrophagic Defense and Autophagy.

Contaminant-bearing fine biochar particles (FBPs) may exert significantly different toxicity profiles from their contaminant-free counterparts. While the role of FBPs in promoting contaminant uptake has been recognized, it is unclear whether the binding of contaminants can modify the biochemical reactivity and toxicological profiles of FBPs. Here, we show that binding of benzo[a]pyrene (B(a)P, a model polycyclic aromatic hydrocarbon) at environmentally relevant exposure concentrations markedly alters the cytotoxicity of FBPs to macrophages, an important line of innate immune defense against airborne particulate matters (PMs). Specifically, B(a)P-bearing FBPs elicit more severe disruption of the phospholipid membrane, endocytosis, oxidative stress, autophagy, and compromised innate immune defense, as evidenced by blunted proinflammatory effects, compared with B(a)P-free FBPs. Notably, the altered cytotoxicity cannot be attributed to the dissolution of B(a)P from the B(a)P-bearing FBPs, but appears to be related to B(a)P adsorption-induced changes of FBPs bioreactivity toward macrophages. Our findings highlight the significance of environmental chemical transformation in altering the bioreactivity and toxicity of PMs and call for further studies on other types of carbonaceous nanoparticles and additional exposure scenarios.

Watershed, climate, and stable isotope data (oxygen-18 and deuterium) for 50 boreal lakes in the oil sands region, northeastern Alberta, Canada, 2002-2017.

Watershed data, climate and stable data collected over a 16-year period from a network of 50 lakes in northeastern Alberta, are provided to allow for broader incorporation into regional assessments of environmental impacts, particularly hydrologic and geochemical processes under changing climate and land use development. Oxygen-18 and deuterium analyses of water samples are provided from late summer surveys of 50 lakes with varying land cover and permafrost conditions. Six sub-groups of lakes are represented, including Stony Mountains, West Fort McMurray, Northeast Fort McMurray, Birch Mountains, Caribou Mountains and Shield. This dataset includes 1582 isotopic analyses made on 791 water samples and 3164 isotope mass balance model outputs, as well as 800 lake/watershed parameters, 5600 climate parameters, and 800 modelled values for isotopic composition of precipitation used in the computations. Model data are provided to facilitate evaluation of transferability of the model for other applications, and to permit more sophisticated spatial analysis and intercomparison with geochemical and biological datasets. Details and further discussion on the isotope mass balance approach are provided in "Regional trends in water balance and runoff to fifty boreal lakes: a 16-year isotope mass balance assessment including evaluation of hydrologic drivers" [1]. Overall, the data are expected to be useful, in comparison with local and regional datasets, for water resource management and planning, including design of monitoring networks and environmental impact assessments for oil sands projects.

Adaptation of plants to high-calcium content kart regions: possible involvement of symbiotic microorganisms and underlying mechanisms / Adaptação de plantas a regiões de kart com alto teor de cálcio: possível envolvimento de microrganismos simbióticos e mecanismos subjacentes

Abstract Rhizosphere microorganisms and endophytes can help their hosts absorb nutrients and regulate the levels of plant hormones. Moreover, they can modulate the expressions of host genes, assist hosts in eliminating reactive oxygen species (ROS) and secreting volatile organic compounds. Therefore, rhizosphere microorganisms and endophytes are considered as determinant factors driving processes involved in the growth of host plants. However, the physiological and ecological functions, as well as the molecular mechanism underlying the behavior of rhizosphere microorganisms and endophytes in their role in the adaptive capacity of host plants in the karstic high-calcium environment have not been systematically studied. This review summarizes the physiological and molecular mechanisms of rhizosphere microorganisms and endophytes which help host plants to adapt to various kinds of adverse environments. The adaptive capacities of plants growing in adverse environments, partly, or totally, depends on microorganisms co-existing with the host plants.

Resumo Os microorganismos e endófitos da rizosfera podem ajudar seus hospedeiros a absorver nutrientes e regular os níveis de hormônios vegetais. Além disso, eles podem modular as expressões dos genes hospedeiros, auxiliar os hospedeiros na eliminação de espécies reativas de oxigênio (ROS) e secretar compostos orgânicos voláteis. Portanto, microorganismos e endófitos da rizosfera são considerados determinantes dos processos envolvidos no crescimento de plantas hospedeiras. No entanto, as funções fisiológicas e ecológicas, bem como o mecanismo molecular subjacente ao comportamento dos microrganismos e endofíticos da rizosfera no seu papel na capacidade adaptativa das plantas hospedeiras no ambiente cárstico de alto teor de cálcio, não foram sistematicamente estudados. Esta revisão resume os mecanismos fisiológicos e moleculares de microrganismos e endófitos da rizosfera que ajudam as plantas hospedeiras a se adaptarem a vários tipos de ambientes adversos. As capacidades adaptativas das plantas que crescem em ambientes adversos, em parte ou totalmente, dependem de microrganismos coexistentes com as plantas hospedeiras.