Begomoviral ßC1 orchestrates organellar genomic instability to augment viral infection.

Chloroplast is the site for transforming light energy to chemical energy. It also acts as a production unit for a variety of defense-related molecules. These defense moieties are necessary to mount a successful counter defense against pathogens, including viruses. Previous studies indicated disruption of chloroplast homeostasis as a basic strategy of Begomovirus for its successful infection leading to the production of vein-clearing, mosaic, and chlorotic symptoms in infected plants. Although begomoviral pathogenicity determinant protein Beta C1 (ßC1) was implicated for pathogenicity, the underlying mechanism was unclear. Here we show that, begomoviral ßC1 directly interferes with the host plastid homeostasis. ßC1 induced DPD1, an organelle-specific nuclease, implicated in nutrient salvage and senescence, as well as modulated the function of a major plastid genome maintainer protein RecA1, to subvert plastid genome. We show that ßC1 was able to physically interact with bacterial RecA and its plant homolog RecA1, resulting in its altered activity. We observed that knocking-down DPD1 during virus infection significantly reduced virus-induced necrosis. These results indicate the presence of a strategy in which a viral protein alters host defense by targeting modulators of chloroplast DNA. We predict that the mechanism identified here might have similarities in other plant-pathogen interactions.

A conserved sequence signature is essential for robust plant miRNA biogenesis.

Micro (mi)RNAs are 20-22nt long non-coding RNA molecules involved in post-transcriptional silencing of targets having high base-pair complementarity. Plant miRNAs are processed from long Pol II-transcripts with specific stem-loop structures by Dicer-like (DCL) 1 protein. Although there were reports indicating how a specific region is selected for miRNA biogenesis, molecular details were unclear. Here, we show that the presence of specific GC-rich sequence signature within miRNA/miRNA* region is required for the precise miRNA biogenesis. The involvement of GC-rich signatures in precise processing and abundance of miRNAs was confirmed through detailed molecular and functional analysis. Consistent with the presence of the miRNA-specific GC signature, target RNAs of miRNAs also possess conserved complementary sequence signatures in their miRNA binding motifs. The selection of these GC signatures was dependent on an RNA binding protein partner of DCL1 named HYL1. Finally, we demonstrate a direct application of this discovery for enhancing the abundance and efficiency of artificial miRNAs that are popular in plant functional genomic studies.

A wound alkalinity measurement to predict non-healing wound outcomes.

OBJECTIVE: As wound pH could influence wound healing rates, this study examined the alkalinity of the entire wound during patients' follow-up visits to predict the final non-healing outcome. METHOD: Wound alkalinity of patients with diabetic foot ulcers (DFUs), venous leg ulcers, and other wounds during three follow-up visits within a four week period was recorded. All wounds were followed until 12 weeks to confirm that healed wounds did not relapse. The alkalinity of various wounds over multiple visits with varying durations was compared with final wound status to assess whether one-time wound alkalinity measurement could predict non-healing wounds. The effect of wound types, infection, age and sex on such determinations was also studied. RESULTS: A total of 96 patients were included in this study. Based on probability variations of pre- and post-test non-healing outcomes from multiple visits over 12 weeks, second visit assessment gave the highest increase in risk of non-healing for an alkaline test result (+8.0%) and decrease in risk of non-healing for a non-alkaline test result (-19.7%). Moreover, a second visit (7-21 days from first visit) showed a greater change in risk for non-healing based on alkaline and non-alkaline test results (+15.7% and -38.1% respectively), compared with a visit within seven days (+6.3% and -12.5%, respectively). Wound type, infection, age and sex did not affect the prognostic ability of wound alkalinity. CONCLUSION: The results of this study support that a single wound alkalinity measurement during the second visit (7-21 days from first visit) can be used to predict non-healing wounds. Wound alkalinity may be routinely assessed to predict non-healing wounds and to determine whether the wounds are healing as expected following initial treatment.

Essential role of γ-clade RNA-dependent RNA polymerases in rice development and yield-related traits is linked to their atypical polymerase activities regulating specific genomic regions.

RNA-dependent RNA polymerases (RDR) generate double-stranded (ds)RNA triggers for RNA silencing across eukaryotes. Among the three clades, α-clade and ß-clade members are key components of RNA silencing and mediators of stress responses across eukaryotes. However, γ-clade members are unusual in that they are represented in phylogenetically distant plants and fungi, and their functions are unknown. Using genetic, bioinformatic and biochemical methods, we show that γ-clade RDRs from Oryza sativa L. are involved in plant development as well as regulation of expression of coding and noncoding RNAs. Overexpression of γ-clade RDRs in transgenic rice and tobacco plants resulted in robust growth phenotype, whereas their silencing in rice displayed strong inhibition of growth. Small (s)RNA and RNA-seq analysis of OsRDR3 mis-expression lines suggested that it is specifically involved in the regulation of repeat-rich regions in the genome. Biochemical analysis confirmed that OsRDR3 has robust polymerase activities on both single stranded (ss)RNA and ssDNA templates similar to the activities reported for α-clade RDRs such as AtRDR6. Our results provide the first evidence of the importance of γ-clade RDRs in plant development, their atypical biochemical activities and their contribution to the regulation of gene expression.

Major Domestication-Related Phenotypes in Indica Rice Are Due to Loss of miRNA-Mediated Laccase Silencing.

Domestication of rice (Oryza sativa) included conversion of perennial wild species with few seeds to short plants that produced abundant seeds. Most domestication-associated changes were due to variations in transcription factors and other key proteins such as enzymes. Here, we show that multiple yield-related traits associated with indica rice domestication are linked to micro (mi) RNA-mediated regulation. Analysis of small (s) RNA data sets from cultivated indica rice lines, a few landraces, and two wild relatives of rice revealed the presence of abundant 22-nucleotide (nt) reads in wild relatives that mapped to miR397 precursors. miR397 was expressed at very high levels in wild relatives and at negligible levels in high-yielding cultivated lines. In its genera-specific form of 22-nt, miR397 targeted mRNAs encoding laccases that decayed and induced robust secondary cascade silencing in wild species that required RNA-dependent RNA polymerase 6. In wild species of rice, reduced expression of laccases resulted in low lignification. As expected, overexpression of miR397 induced de-domestication phenotypes. At least 26 uncharacterized QTLs previously implicated in rice yield overlapped with laccases and miR397 genes. These results suggest that miRNAs contribute to rice domestication-associated phenotypes.

A non-contact device for fast screening of wound infections.

Screening for wound infection relies on the expertise of the provider. Clinical diagnosis of infections based on wound swab/biopsy results often takes a few days and may not assess the full wound. There is a need for a non-invasive tool that can quickly and accurately diagnose wound infection. Leukocyte esterase strips are used to identify various infectious diseases. However, it is not clear whether infected wounds also have elevated leukocyte esterase activities as compared with non-infected wounds. To achieve the objective, a device was developed to detect elevated leukocyte esterase activities in wounds by measuring wound exudates adsorbed onto wound dressings in 3 minutes. The efficacy of the device in assessing leukocyte esterase activities across various chronic wounds was tested. Such measurements were unaffected by the type of underlying wound dressing. By correlating the device outputs with clinical adjudication of infection, we found that this device had high positive predictive values for diagnosing wound infection in a wide variety of chronic wounds. In addition, a positive device output increases the probability of detecting infected wounds, while the negative device output reduces the probability of detecting infected wounds. This rapid non-contact and disposable diagnostic tool may serve as a rapid and accurate indication of infection in the chronic wound.

Influence of scaffold design on host immune and stem cell responses.

The combined culture of isolated stem cells in tissue engineering scaffolds represents a popular strategy for the regeneration of specialized tissues. Despite of improved outcomes in some tissues, this stem cell-seeded tissue engineering strategy has not led to significant tissue regeneration as expected. The lower-than-expected outcome may be caused by overwhelming immune responses to scaffold materials and poor survival of seeded stem cells following implantation. This review is aimed at summarizing the success and failure of this strategy and also shedding some light on new directions to design scaffolds for promoting regenerative responses via autologous stem cells. The first half of this review summarizes the influence of scaffold physical and chemical properties on immune cell responses to scaffold implants. The second half focuses on the influence of scaffold design to alter immune and stem cell responses for achieving desirable tissue regeneration.

Stability of Begomoviral pathogenicity determinant ßC1 is modulated by mutually antagonistic SUMOylation and SIM interactions.

BACKGROUND: To successfully invade new hosts, plant viruses must break host resistance and be competent to move within and between plant cells. As a means, viral proteins known as pathogenicity determinants have evolved to coordinate a network of protein interactions. The ßC1 protein encoded by specific geminiviral satellites acts as a key pathogenicity determinant for this disease-causing family of plant viruses. Post-translational modifications (PTMs) such as ubiquitination and phosphorylation of the ßC1 protein have been shown to occur in diverse viruses. However, the relevance of these and other layers of PTMs in host-geminiviral interactions has not been fully understood. RESULTS: Here we identified the significance of a novel layer of PTMs in the ßC1 protein of Synedrella yellow vein clearing virus (SyYVCV), a newly identified member of the Begomovirus genus of Geminiviruses. This protein has conserved SUMOylation and SUMO-interacting motifs (SIMs), and we observed SUMOylation of SyYVCV ßC1 in host plants as a defensive strategy against ubiquitin-mediated degradation. Counteracting this, SIMs encoded in ßC1 mediate the degradation of ßC1; however, both these PTMs are essential for the function of ßC1 protein since SIM and SUMOylation motif mutants failed to promote pathogenicity and viral replication in vivo. SUMOylation in different motifs of ßC1 led to functionally distinct outcomes, regulating the stability and function of the ßC1 protein, as well as increased global SUMOylation of host proteins. CONCLUSION: Our results indicate the presence of a novel mechanism mediating a fine balance between defence and counter-defence in which a SIM site is competitively sought for degradation and, as a counter-defence, ßC1 undergoes SUMOylation to escape from its degradation.

miR828 and miR858 regulate VvMYB114 to promote anthocyanin and flavonol accumulation in grapes.

MicroRNAs are a class of non-coding small RNAs involved in the negative regulation of gene expression, which play critical roles in developmental and metabolic pathways. Studies in several plants have identified a few microRNAs and other small RNAs that target regulators of the phenylpropanoid metabolic pathway called the MYB transcription factors. However, it is not well understood how sRNA-mediated regulation of MYBs influences the accumulation of specific secondary metabolites. Using sRNA sequencing, degradome analysis, mRNA sequencing, and proteomic analysis, we establish that grape lines with high anthocyanin content express two MYB-targeting microRNAs abundantly, resulting in the differential expression of specific MYB proteins. miR828 and miR858 target coding sequences of specific helix motifs in the mRNA sequences of MYB proteins. Targeting by miR828 caused MYB RNA decay and the production of a cascade of secondary siRNAs that depend on RNA-dependent RNA polymerase 6. MYB suppression and cascade silencing was more robust in grape lines with high anthocyanin content than in a flavonol-rich grape line. We establish that microRNA-mediated silencing targeted the repressor class of MYBs to promote anthocyanin biosynthesis in grape lines with high anthocyanins. We propose that this process regulates the expression of appropriate MYBs in grape lines to produce specific secondary metabolites.

Gold(III) NHC Complexes for Catalyzing Dihydroalkoxylation and Hydroamination Reactions.

A gold(III) complex of an N-heterocyclic carbene based hemilabile ligand with two pendant pyrazole arms (1,3-bis((1H-pyrazol-3-yl)methyl)-2,3-dihydro-1H-imidazole, LH) was synthesized. Complex [LAu(III)Cl3] is an excellent catalyst for promoting dihydroalkoxylation at room temperature, even catalyzing this reaction at 0 °C. [LAu(III)Cl3] is one of the most efficient catalysts reported to date for the spirocyclization of alkynyl diols. Furthermore, [LAu(III)Cl3] catalyzed intra- and intermolecular hydroamination reactions, achieving good to excellent conversions. [LAu(III)Cl3] is a more efficient catalyst than a gold(I) analogue, [LAu(I)Cl]. The dependence of the quantity of weakly coordinating anion [BArF4]- ((3,5-trifluoromethyl)phenyl borate) present on catalysis efficiency was probed for the dihydroalkoxylation reaction. X-ray diffraction analysis of single crystals demonstrated the solid-state structure of gold complexes [LAu(III)Cl3] and [LAu(I)Cl], which displayed the expected square-planar and linear coordination geometries, respectively.

Wound-induced small-peptide-mediated signaling cascade, regulated by OsPSKR, dictates balance between growth and defense in rice.

Wounding is a general stress in plants that results from various pest and pathogenic infections in addition to environment-induced mechanical damages. Plants have sophisticated molecular mechanisms to recognize and respond to wounding, with those of monocots being distinct from dicots. Here, we show the involvement of two distinct categories of temporally separated, endogenously derived peptides, namely, plant elicitor peptides (PEPs) and phytosulfokine (PSK), mediating wound responses in rice. These peptides trigger a dynamic signal relay in which a receptor kinase involved in PSK perception named OsPSKR plays a major role. Perturbation of OsPSKR expression in rice leads to compromised development and constitutive autoimmune phenotypes. OsPSKR regulates the transitioning of defense to growth signals upon wounding. OsPSKR displays mutual antagonism with the OsPEPR1 receptor involved in PEP perception. Collectively, our work indicates the presence of a stepwise peptide-mediated signal relay that regulates the transition from defense to growth upon wounding in monocots.

Novel regulators of mitochondrial genome integrity.

Mitochondrial genomes are unusual in that they have very low mutation rates in coding sequences when compared with animals, yeast, and bacteria. It has been proposed that the mitochondrial (mt) DNA damage is preferentially repaired by homologous recombination (HR). In this short review, we summarize and discuss the well-established and recently identified pathways that help in maintaining the integrity of plant mitochondrial genomes.

Mechanism and therapeutic implications of pomalidomide-induced immune surface marker upregulation in EBV-positive lymphomas.

Epstein-Barr virus (EBV) downregulates immune surface markers to avoid immune recognition. Pomalidomide (Pom) was previously shown to increase immune surface marker expression in EBV-infected tumor cells. We explored the mechanism by which Pom leads to these effects in EBV-infected cells. Pom increased B7-2/CD86 mRNA, protein, and surface expression in EBV-infected cells but this was virtually eliminated in EBV-infected cells made resistant to Pom-induced cytostatic effects. This indicates that Pom initiates the upregulation of these markers by interacting with its target, cereblon. Interestingly, Pom increased the proinflammatory cytokines IP-10 and MIP-1∝/ß in EBV infected cells, supporting a possible role for the phosphoinositide 3-kinase (PI3K)/AKT pathway in Pom's effects. Idelalisib, an inhibitor of the delta subunit of PI3 Kinase, blocked AKT-Ser phosphorylation and Pom-induced B7-2 surface expression. PU.1 is a downstream target for AKT that is expressed in EBV-infected cells. Pom treatment led to an increase in PU.1 binding to the B7-2 promoter based on ChIP analysis. Thus, our data indicates Pom acts through cereblon leading to degradation of Ikaros and activation of the PI3K/AKT/PU.1 pathway resulting in upregulation of B7-2 mRNA and protein expression. The increased immune recognition in addition to the increases in proinflammatory cytokines upon Pom treatment suggests Pom may be useful in the treatment of EBV-positive lymphomas.

Role of fluoroquinolone prophylaxis in allogeneic hematopoietic cell transplantation in regions with a high prevalence of fluoroquinolone resistance.

Introduction: The role of fluoroquinolone (FQ) prophylaxis in preventing gram-negative bacilli (GNB) bacteremia, graft-versus-host disease (GVHD), and overall survival (OS) after allogeneic hematopoietic cell transplantation (allo-HCT) is debatable and may differ in settings with low and high prevalences of FQ resistance. In this study, we aimed to answer this question in regions with high FQ resistance. Methods: This single-center retrospective study included all consecutive allo-HCT recipients aged ≥12 years from 2012 to 2021. Allo-HCT recipients until 2016 were administered FQ prophylaxis (levofloxacin). After 2016, the institutional protocol was modified to no antibiotic prophylaxis. Data were retrieved from patient records for disease and transplant characteristics, the incidence of GNB bacteremia, duration of parenteral antibiotics, hospitalization duration, acute GVHD, and OS. Results: A total of 135 allo-HCT recipients (43 in the FQ-prophylaxis cohort and 92 in the no-antibiotic prophylaxis cohort) were analyzed in this study. The two cohorts were matched for age (median, 26 vs. 24.5 years; p = 0.8). The no-antibiotic prophylaxis cohort had a higher proportion of malignant diagnoses (80% vs. 58%, p = 0.01), haploidentical transplants (46% vs. 14%, p = 0.004), and posttransplant cyclophosphamide exposure (46% vs. 14%, p = 0.003) than did the FQ cohort. Despite this, the incidence of GNB bacteremia was not significantly different between the two cohorts (37% vs. 34%, p = 0.6). There were no differences in parenteral antibiotic use or hospitalization duration, as well as the incidence of acute GVHD (53% vs. 53%, p = 0.3). The 1-year OS was similar between the two cohorts (66% vs. 67%, p = 0.6). Conclusion: This study shows that FQ prophylaxis did not affect the incidence of GNB bacteremia, parenteral antibiotic use, hospitalization duration, acute GVHD, and OS post-allo-HCT.

Diagnostics for Wound Infections.

Significance: Infections can significantly delay the healing process in chronic wounds, placing an enormous economic burden on health care resources. Identification of infection biomarkers and imaging modalities to observe and quantify them has seen progress over the years. Recent Advances: Traditionally, clinicians determine the presence of infection through visual observation of wounds and confirm their diagnosis through wound culture. Many laboratory markers, including C-reactive protein, procalcitonin, presepsin, and bacterial protease activity, have been quantified to assist diagnosis of infection. Moreover, imaging modalities like plain radiography, computed tomography, magnetic resonance imaging, ultrasound imaging, spatial frequency domain imaging, thermography, autofluorescence imaging, and biosensors have emerged for real-time wound infection diagnosis and showed their unique advantages in deeper wound infection diagnosis. Critical Issues: While traditional diagnostic approaches provide valuable information, they are time-consuming and depend on clinicians' experiences. There is a need for noninvasive wound infection diagnostics that are highly specific, rapid, and accurate, and do not require extensive training. Future Directions: While innovative diagnostics utilizing various imaging instrumentation are being developed, new biomarkers have been investigated as potential indicators for wound infection. Products may be developed to either qualitatively or quantitatively measure these biomarkers. This review summarizes and compares all available diagnostics for wound infection, including those currently used in clinics and still under development. This review could serve as a valuable resource for clinicians treating wound infections as well as patients and wound care providers who would like to be informed of the recent developments.

Stability of surfactant-laden liquid film flow over a cylindrical rod.

The stability of surfactant-laden liquid film flow over a cylindrical rod is examined in creeping flow limit using standard temporal linear stability analysis. The clean film flow configuration (i.e., in absence of surfactant) is well-known to become unstable owing to Rayleigh-Plateau instability of cylindrical liquid interfaces. Previous studies demonstrated that for a static liquid film (i.e., zero basic flow) coating a rod, the presence of interfacial surfactant decrease the growth of Rayleigh-Plateau instability, but is unable to suppress it completely. Further, the presence of interfacial surfactant is known to introduce an additional mode, referred to as surfactant mode in the present work. To the best of our knowledge, the stability of surfactant mode has not been analyzed in the context of cylindrical film flows. Thus, we reexamined the stability of surfactant-laden cylindrical liquid film flow to analyze the stability behavior of the above said two modes when the basic flow is turned on. The present study reveals that the incorporation of basic flow in stability analysis leads to the complete suppression of Rayleigh-Plateau instability due to the presence of interfacial surfactants as compared to the partial suppression obtained for a stationary liquid film. Three nondimensional parameters appear for this problem: Bond number (denoted as Bo) which characterizes the strength of basic flow, Marangoni number (denoted as Ma) which signifies the presence of surfactant, and ratio of rod radius to film thickness denoted as S. In creeping flow limit, the characteristic equation is quadratic with one root belonging to Rayleigh-Plateau mode and the other to surfactant mode. We first carried out an asymptotic analysis to independently capture the eigenvalues corresponding to both the modes in limit of long-wave disturbances. The long-wave results show that the Rayleigh-Plateau instability is completely suppressed on increasing the Marangoni number above a critical value while the surfactant mode always remains stable in low wave-number limit. The continuation of long-wave results to arbitrary wavelength disturbances show that the suppression of Rayleigh-Plateau instability mode still holds, however, the surfactant mode becomes unstable at sufficiently high values of Marangoni number. Further, this surfactant mode instability shifts toward low wave numbers with critical Marangoni number for instability scaling with wave number in a particular fashion. We used this scaling and carried out an asymptotic analysis to capture this instability in low wave-number limit. Depending on S and Bo, we observed the existence of a stable gap in terms of Ma where both the eigen-modes remain stable. Our results indicate that for a given Bond number, the width of stable gap in terms of Ma decreases with decrease in S and the stable gap vanishes when S is sufficiently small. The effect of increasing Bond number (or equivalently, the strength of basic flow) is found to be stabilizing for the film flow configuration.

Loss of function of Oryza sativa Argonaute 18 induces male sterility and reduction in phased small RNAs.

KEY MESSAGE: In this manuscript, we show that Oryza sativa indica Argonaute protein AGO18 is required for male gametophyte development likely to through a small RNA-mediated mechanism. Monocots have evolved unique gene silencing pathways due to the presence of unique members of Dicer-like and Argonaute (AGO) family members. Among the monocot AGO homologs, AGO18 occupies a unique position. Previous reports have implicated this protein in viral resistance as well as in gametogenesis, likely through its competition with AGO1 clade members for micro(mi)RNAs and other small (s)RNAs. Although expression of rice AGO18 in specific stages of male gametogenesis has been documented, its major functions in plant development remain poorly understood. Here, we show that Oryza sativa indica AGO18 is involved in male gametophyte development. Knockdown (KD) of AGO18 in transgenic rice lines resulted in stunted plants that are male sterile, whereas their carpels were functional. Transcriptome analysis revealed downregulation of several pollen development-associated genes in KD lines. sRNA sequencing in vegetative and reproductive tissues of KD lines indicated reduction of miRNAs and phased secondary sRNAs implicated in male gametophyte development. Our results indicate a distinct role for rice AGO18 in male fertility.

Imaging in Chronic Wound Diagnostics.

Significance: Chronic wounds affect millions of patients worldwide, placing a huge burden on health care resources. Although significant progress has been made in the development of wound treatments, very few advances have been made in wound diagnosis. Recent Advances: Standard imaging methods like computed tomography, single-photon emission computed tomography, magnetic resonance imaging, terahertz imaging, and ultrasound imaging have been widely employed in wound diagnostics. A number of noninvasive optical imaging modalities like optical coherence tomography, near-infrared spectroscopy, laser Doppler imaging, spatial frequency domain imaging, digital camera imaging, and thermal and fluorescence imaging have emerged over the years. Critical Issues: While standard diagnostic wound imaging modalities provide valuable information, they cannot account for dynamic changes in the wound environment. In addition, they lack the capability to predict the healing outcome. Thus, there remains a pressing need for more efficient methods that can not only indicate the current state of the wound but also help determine whether the wound is on track to heal normally. Future Directions: Many imaging probes have been fabricated and shown to provide real-time assessment of tissue microenvironment and inflammatory responses in vivo. These probes have been demonstrated to noninvasively detect various changes in the wound environment, which include tissue pH, reactive oxygen species, fibrin deposition, matrix metalloproteinase production, and macrophage accumulation. This review summarizes the creation of these probes and their potential implications in wound monitoring.

A Device to Predict Short-Term Healing Outcome of Chronic Wounds.

Objective: While myriads of studies have suggested that a survey of wound pH environment could indicate wound healing activities, it is not clear whether wound alkalinity can be used as a prognostic indicator of nonhealing wounds. Currently available systems cannot reliably assess the pH environment across wounds, which is the objective of this study. Approach: A disposable device, DETEC® pH, was developed and characterized on its ability to map wound alkalinity by pressing a freshly recovered wound dressing against its test surface. By comparing the wound's alkalinity and size reduction rates (∼7 days) following pH measurement, we assessed the capability of wound alkalinity to prognosticate subsequent short-term wound size reduction rates. Results: The device had high accuracy and specificity in determining the alkalinity of simulated wound fluids soaked onto wound dressing. The type of wound dressing type had an insignificant effect on its detection sensitivity. Upon testing discarded wound dressings from human patients, the device quickly determined alkaline and acidic wounds. Finally, statistical analyses of wound size reduction rates in wounds with various alkalinities confirmed that wound alkalinity has a strong influence on, at least, short-term wound healing activity. Innovation: Without directly contacting the patient, this device provides a quick assessment of wound alkalinity to prognosticate immediate and short-term wound healing activities. Conclusion: DETEC® pH may serve as a prognosis device for wound care specialists during routine wound assessment to predict wound healing progress. This information can assist the decision-making process in a clinical setting and augur well for chronic wound treatment. DETEC® pH can also be used as an aid for home health care nurses or health care providers to screen nonhealing wounds outside clinics.

Chemokine releasing particle implants for trapping circulating prostate cancer cells.

Prostate cancer (PCa) is the most prevalent cancer in U.S. men and many other countries. Although primary PCa can be controlled with surgery or radiation, treatment options of preventing metastatic PCa are still limited. To develop a new treatment of eradicating metastatic PCa, we have created an injectable cancer trap that can actively recruit cancer cells in bloodstream. The cancer trap is composed of hyaluronic acid microparticles that have good cell and tissue compatibility and can extend the release of chemokines to 4 days in vitro. We find that erythropoietin (EPO) and stromal derived factor-1α can attract PCa in vitro. Animal results show that EPO-releasing cancer trap attracted large number of circulating PCa and significantly reduced cancer spreading to other organs compared with controls. These results support that cancer trap may serve as a unique device to sequester circulating PCa cells and subsequently reduce distant metastasis.