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Viruses are important components of the human body. Growing evidence suggests that they are engaged in the physiology and disease status of the host. Even though the vaginal microbiome is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, little is known about the role of the vaginal virome. In this pilot exploratory study, using unbiased viral metagenomics, we aim to investigate the vaginal eukaryotic virome in women with different levels of cervical lesions, and examine their associations with different cervical disease status. An altered eukaryotic virome was observed in women with different levels of lesions and Lactobacillus profiles. Anelloviruses and papillomaviruses are the most commonly detected eukaryotic viruses of the vaginal virome. Higher abundance and richness of anelloviruses and papillomaviruses were associated with low-grade squamous intraepithelial lesion (LSIL) and CC. Besides, higher anellovirus abundance was also associated with lactobacillus-depleted microbiome profiles and bacterial community state (CST) type IV. Furthermore, increased correlations between Anelloviridae and Papillomaviridae occurred in the women with increased cervical disease severity level from LSIL to CC. These data suggest underlying interactions between different microbes as well as the host physiology. Higher abundance and diversity of both anelloviruses and papillomaviruses shared by LSIL and CC suggest that anellovirus may be used as a potential adjunct biomarker to predict the risk of HPV persistent infection and/or CC. Future studies need to focus on the clinical relevance of anellovirus abundance with cervical disease status, and the evaluation of their potential as a new adjunct biomarker for the prediction and prognoses of CC.

Much attention has been devoted to the synthesis and antimicrobial studies of nanopatterned surfaces. However, factors contributing to their potential and eventual application, such as large-scale synthesis, material durability, and biocompatibility, are often neglected in such studies. In this paper, the ZnO nanopillar surface is found to be amenable to synthesis in large forms and stable upon exposure to highly accelerated lifetime tests (HALT) without any detrimental effect on its antimicrobial activity. Additionally, the material is effective against clinically isolated pathogens and biocompatible

Yanyun Li,1,&ast; Ying-Xin Gong,1,&ast; Qing Wang,1 Shujun Gao,1 Hongwei Zhang,1 Feng Xie,1 Qing Cong,1 Limei Chen,1 Qi Zhou,1 Zubei Hong,2 Lihua Qiu,2 Fang Li,3 Yu Xie,1 Long Sui1 1Department of Gynecology and Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Gynecology and Obstetrics, Renji Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Gynecology and Obstetrics, Shanghai Dongfang Hospital of Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Long Sui; Yu XieObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai, 200011, People’s Republic of ChinaTel +86-21-33189900Fax +86-21-63450900Email suilong@fudan.edu.cn; yuxie18@fudan.edu.cnPurpose: Early-stage cervical cancer is usually diagnosed by colposcopy-directed biopsy (CDB) and/or endocervical curettage (ECC), but some neglected lesions must be detected by conization because they are occult. This study aimed to explore the optimal method for detecting these “occult” cervical cancers.Patients and Methods: A total of 1299 patients who were high-risk for early-stage cervical cancer from five centres in China were prospectively included. We evaluated the diagnostic performance of cytology, HPV testing, colposcopy and CDB&ECC for detecting “occult” cervical cancer and discussed the diagnostic importance of transformation zone (TZ) type, conization length and the proportion of cervical cone excision.Results: The diagnostic agreement between colposcopy impression and conization was 64.5% and 72.4% between CDB&ECC and conization. Forty-two patients were finally diagnosed with pathologic cancer, and the sensitivities of cytology, colposcopy, CDB&ECC were 4.8%, 7.1%, and 47.4%, respectively. Twenty cases were neglected by CDB&ECC but further diagnosed as cancer by conization, considered to be occult cervical cancer, accounting for 1.6%. Cytologic high-grade squamous intraepithelial lesion (HSIL)+, positive HPV, biopsy HSIL+ and cervical TZ type 3 were considered risk factors for developing HSIL+, while colposcopy impression HSIL+ was not. There was a significant difference between cancerous and HSIL patients in the proportion of cervical cone excision (P< 0.001), which was recognized as a risk factor (P< 0.001) for detecting cancer, while the length of cervical cone excision was not. The average proportion was 0.62, and the minimal effective proportion was 0.56.Conclusion: Since the incidence of occult cervical cancer neglected by CDB&ECC, colposcopy and cytology was far beyond expectations, conization is necessary, especially in patients with TZ type 3, high-grade cytology and biopsy results. As the cervical length varies in patients, the proportion of cervical cone excision might be a better indicator for detecting occult cervical cancer.Keywords: cervical conization, colposcopy-directed biopsy, high-grade intraepithelial lesion, length proportion, occult cervical cancer, transformation zone

Background Mullerian anomalies take many forms of manifestation. The oblique cervical septum with a complete uterine septum (OCSCUS), as a rare form of Mullerian anomaly, has never been reported in the literature. Case A 10-year-old female adolescent presented with progressive abdominal pain after the onset of menarche was diagnosed as OCSCUS using magnetic resonance imaging and treated with hysteroscopic dissection of the uterine part of the septum. Summary and Conclusion Greater awareness of the OCSCUS will lead to earlier detection and is the key to alleviating patient suffering and avoiding potentially severe complications, such as endometriosis and infertility. For the treatment of OCSCUS, hysteroscopic dissection of the uterine part of the septum is a minimally invasive treatment choice with low surgical risk.

We report the design, synthesis, and evaluation of biodegradable amphiphilic poly(ethylene glycol)-b-polycarbonate-based diblock copolymers containing pendant persistent organic radicals (e.g., PROXYL). These paramagnetic radical-functionalized polymers self-assemble into micellar nanoparticles in aqueous media, which preferentially accumulate in tumor tissue via the enhanced permeability and retention (EPR) effect. Through T1 relaxation NMR studies, as well as magnetic resonance imaging (MRI) studies on mice, we show that these nanomaterials are effective as metal-free, biodegradable MRI contrast agents. We also demonstrate anticancer drugs can be readily loaded into the nanoparticles, conferring therapeutic delivery properties in addition to their imaging properties making these materials potential theranostic agents in the treatment of cancer.

Preeclampsia (PE) is characterized by gestational hypertension and proteinuria, and is a leading cause of maternal death and perinatal morbidity globally. Although the exact cause of PE remains unclear, several studies have suggested a role for abnormal expression of multiple genes. The aim of the present study was to identify key genes and related pathways, and to screen for drugs that regulate these genes for potential PE therapy. The GSE60438 dataset was acquired from the Gene Expression Omnibus database to analyze differentially expressed genes (DEGs). By constructing a protein-protein interaction network and performing reverse transcription-quantitative PCR verification, proteasome 26S subunit, non-ATPase 14, prostaglandin E synthase 3 and ubiquinol-cytochrome c reductase core protein 2 were identified as key genes in PE. In addition, PE was found to be associated with ‘circadian rhythm’, ‘fatty acid metabolism’, ‘DNA damage response detection of DNA damage’, ‘regulation of DNA repair’ and ‘endothelial cell development’. Through connectivity map analysis of DEGs, furosemide and droperidol were suggested to be therapeutic drugs that may target the hub genes for PE treatment. Results analysis of GSEA were included in the discussion section of this article. In conclusion, the current study identified novel key genes associated with the onset of PE and potential drugs for PE treatment.

Barium sulfate deposition is one of the most serious problems in the flow assurance issues in the industry. The kinetics of barium sulfate deposition inside the flowing tubing has been studied. The...

An acid-resistant DNA hydrogel that is stable in an extremely acidic environment with pH as low as 1.2 has not been reported before, largely due to the instability of DNA-hybridized structures. To achieve this, adenine (A)-rich and cytosine (C)-rich oligonucleotides are rationally designed and integrated to form copolymers with acrylamide monomers

Printed Circuit Board Assembly (PCBA) plays an important role in 3C (Computer, Communication and Consumer Electronics) industry. The object detection of electronic components is the key technology for flaw inspection and quality control of PCBA. YOLOv3 has been widely used in object detection. Image pre-processing can eliminate some distractions and prominent some feature to improve the detection accuracy. The tailored YOLOv3 has a smaller computational cost and transfer learning can accelerate the training speed and improve inspection accuracy.

SMT (surface mounted technology) is the most popular technology and process in the electronic assembly industry. Chip resistors are widely used in this technology. Printing characters recognition of chip resistors can inspect the specification of the resistors and check whether the chip resistors are mounted on the correct location. The traditional image segmentation methods are used to extract the printing characters from the images of chip resistors. And then the extracted characters are input an artificial neural network model and recognized. The combination of image segmentation and neural network has high accuracy and efficiency.

Scale inhibitors are widely used to prevent mineral scale deposition and precipitation in industrial processes. In this study, the performance of scale inhibitors is systematically investigated in ...

Cancer stem cells (CSCs) have been much proposed as potential tumor eradication targets since they possess highly tumorigenic qualities. However, efficient and fast enrichment of CSCs for cancer biology study and drug screening has been challenging. CD44 is a cell surface receptor for hyaluronic acid (HA) and has been reported as an important CSC marker. Here, we show a simple and label-free method for the enrichment of CSCs highly expressing CD44 using enzymatically crosslinked HA hydrogels. HA hydrogels were formed with different crosslink densities to modulate the interaction between the CD44 and HA chains. We show that HA hydrogels with defined crosslink densities isolated cancer cells expressing high CD44 from breast cancer cell lines in a facile, efficient manner. The enriched cells exhibited CSC-like characteristics such as high expression of CSC markers (octamer-binding transcription factor 4 (OCT4) and aldehyde dehydrogenase 1 (ALDH1)), enhanced tumorsphere formation and chemoresistance. The enriched cells also displayed strong tumorigenicity, metastatic potential and poor survival in vivo. The HA hydrogel provides a simple, fast and efficient platform for CSC enrichment and promotes new anticancer strategies that target breast CSCs. STATEMENT OF SIGNIFICANCE: There is strong interest in developing isolation methods for cancer stem cells (CSCs), due in growing desire for CSC eradication for promising cancer therapy. Tumor sphere formation and fluorescence-activated cell sorting have been widely used for CSC isolation, while these methods require cultivation for several days and labelling of cell surface proteins, respectively. A simple and label-free method for breast CSC isolation is developed using HA-based hydrogels with tunable crosslink density. The efficient enrichment of breast CSCs is achieved by HA-CD44 specific interaction, which is controlled by hydrogel crosslink density. We believe that the simple approach that isolates cells with CSC-like characteristics would facilitate the anticancer drug development and cancer research.

Although a few nanomedicines have been approved for clinical use in cancer treatment, that recognizes improved patient safety through targeted delivery, their improved efficacy over conventional drugs has remained marginal. One of the typical drawbacks of nanocarriers for cancer therapy is a low drug-loading capacity that leads to insufficient efficacy and requires an increase in dosage and/or frequency of administration, which in turn increases carrier toxicity. In contrast, elevating drug-loading would cause the risk of nanocarrier instability, resulting in low efficacy and off-target toxicity. This intractable drug-to-carrier ratio has imposed constraints on the design and development of nanocarriers. However, if the nanocarrier has intrinsic therapeutic effects, the efficacy would be synergistically augmented with less concern for the drug-to-carrier ratio. Sunitinib-loaded micellar nanocomplex (SU-MNC) was formed using poly(ethylene glycol)-conjugated epigallocatechin-3-O-gallate (PEG-EGCG) as such a carrier. SU-MNC specifically inhibited the vascular endothelial growth factor-induced proliferation of endothelial cells, exhibiting minimal cytotoxicity to normal renal cells. SU-MNC showed enhanced anticancer effects and less toxicity than SU administered orally/intravenously on human renal cell carcinoma-xenografted mice, demonstrating more efficient effects on anti-angiogenesis, apoptosis induction, and proliferation inhibition against tumors. In comparison, a conventional nanocarrier, SU-loaded polymeric micelle (SU-PM) comprised of PEG-b-poly(lactic acid) (PEG-PLA) copolymer, only reduced toxicity with no elevated efficacy, despite comparable drug-loading and tumor-targeting efficiency to SU-MNC. Improved efficacy of SU-MNC was ascribed to the carrier-drug synergies with the high-performance carrier of PEG-EGCG besides tumor-targeted delivery.

Apomorphine (AMP, used for treatment of Parkinson's disease) is susceptible to oxidation. Its oxidized products are toxic. To overcome these issues, AMP was conjugated to phenylboronic acid-functionalized polycarbonate through pH-sensitive covalent boronate ester bond between phenylboronic acid and catechol in AMP. Various conditions (use of base as catalyst, reaction time and initial drug loading) were optimized to achieve high AMP conjugation degree and mitigate polymer degradation caused by amine in AMP. Pyridine accelerated AMP conjugation and yielded ~74% conjugation within 5 min. Tertiary amine groups were incorporated to polycarbonate, and served as efficient catalyst (~80% conjugation within 5 min). AMP-conjugated polymer self-assembled into nanoparticles. AMP release from the nanoparticles was minimal at pH 7.4, while in acidic environment (endolysosomes) rapid release was observed. Encapsulation protected AMP from oxidization. The nanoparticles were significantly accumulated in the brain tissue after intranasal delivery. These AMP-loaded nanoparticles have potential use for treatment of Parkinson's disease.

Although mortality continues to decline over the past two decades, cancer is still a pervasive healthcare problem worldwide due to the increase in the number of cases, multidrug resistance (MDR) and metastasis. As a consequence of multidrug resistance, cancer treatment must rely on a host of chemotherapeutic agents and chemosensitizers to achieve remission. To overcome these problems, a series of biodegradable triblock copolymers of PEG, guanidinium-functionalized polycarbonate and polylactide (PEG-PGC x -PDLA y ) is designed as chemotherapeutic agents. These copolymers self-assemble into micellar nanoparticles, and are highly effective against various cancer cell lines including human breast cancer (BCap37), liver cancer (HepG2), lung cancer (A549) and epidermoid carcinoma (A431) cell lines as well as MDR Bats-72 and Bads-200 cancer cells that were developed from BCap37. Multiple treatments with the polymers at sub-lethal doses do not induce resistance. The polymers kill cancer cells by a non-apoptotic mechanism with significant vacuolization and subsequent membrane disruption. In vivo antitumor efficacy is evaluated in a metastatic 4T1 subcutaneous tumor model. Treatment with stereocomplexes of PEG-PGC 43 -PLLA 19 and PEG-PGC 43 -PDLA 20 at a dose of 20 mg/kg of mouse body weight suppresses tumor growth and inhibits tumor metastasis in vivo . These polymers show promise in the treatment of cancer without the onset of resistance.

Asset integrity for oil and gas operations requires reliable chemical information to troubleshoot factors affecting chemical deliverability and performance. Accurate and precise measurement of corrosion inhibitor (CI) concentration in oilfield brine is significant to asset management. However, historically CI residual measurements are extremely problematic due to the surface-active nature of the chemicals which interact with a host of factors that parasitically deplete the CI solution concentration. It is typical to see >100% error on traditional residual measurements especially where dye transfer techniques are concerned. Current methods and sample handling for measuring residuals involves sending samples to a local laboratory for analysis. This time delay can add to the measurement error due to loss of inhibitor species to the sample container or solids that may form in transport. This paper describes the use of a simple, portable, handheld, onsite, nanotechnology-based, residual method to measure CI concentrations in oilfield brines. With more frequent and highly accurate CI residual feedback operators can react to system conditions that threaten to impact asset integrity. Using the CI residual data provided by a rapid, accurate analytical method, operators could extend asset life and prevent failures long before they become critical.

In order to fulfill the market requirements of a well- known citrus market, this paper uses artificial neural network technology to identify the maturity of the citrus fruits, especially the citrus fruits in Xinhui, China. The proposed method has the characteristics of non-contact, low cost, easy implementation and good performance, which can be effectively used in remote monitoring. Also, the AI recognized maturity is practically significant to agricultural production in the recording of citrus growth and forecasting of market sales.

To investigate the complexity of proteomics in cervical cancer tissues, we used isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry analysis on a panel of normal cervical tissues (N), high-grade squamous intraepithelial lesion tissues (HSIL) and cervical cancer tissues (CC). Total 72 differentially expressed proteins were identified both in CC vs N and CC vs HSIL. The expression of HMGB2 was markedly higher in CC than that in HSIL and N. High HMGB2 expression was significantly correlated with primary tumor size, invasion and tumor stage. The up-regulated HMGB2 was discovered to be associated with human cervical cancer. These findings suggest that HMGB2 may be a potentially prognostic biomarker and a target for the therapy of cervical cancer.

Additional file 1: Table S1. The HPV information of the samples. Figure S1. The representative microphotographs of IRS score 1, 2 and 3 for HMGB2.

In this study, biodegradable cationic polycarbonate and polylactide block copolymers were synthesized and successfully used as novel vaccine adjuvants to provide enhanced anticancer immunity. The polymers formed nanoparticles with the model vaccine, ovalbumin (OVA), and the immunostimulant toll-like receptor 3 agonist poly(I:C) (a synthetic analog of the double-stranded RNA). Higher uptake of poly(I:C) by the bone marrow-derived dendritic cells and macrophages and OVA by dendritic cells was observed when delivered using the polymer adjuvant. In vivo experiments showed that these nanoparticles remained longer in the subcutaneous injection site as compared to OVA alone and led to higher production of anti-OVA specific antibodies with prolonged immunostimulation. When OVA was combined with poly(I:C) that was either co-entrapped in the same particles or as separate particles, a comparable level of anti-OVA IgG1 antibodies and interleukin-6 (IL-6) was produced in mouse blood plasma, and a similar level of cytotoxic T lymphocyte (CTL) response in mice was stimulated as compared to OVA/Alum particles. Furthermore, tumor rejection in the mice that were vaccinated for 9 months with the formulations containing the polymer adjuvant was stronger than the other treatment groups without the polymer. Notably, the cationic polycarbonates were not associated with any adverse in vivo effects. Thus, these biodegradable polymers may be promising substitutes for aluminum-based adjuvants in vaccine formulations.

Much attention has been paid to a newly discovered subset of memory T (TM) cells-stem cell-like memory T (TSCM) cells for their high self-renewal ability, multi-differentiation potential and long-term effector function in adoptive therapy against tumors. Despite their application in cancer therapy, an excess of TSCM cells also contributes to the persistence of autoimmune diseases for their immune memory and HIV infection as a long-lived HIV reservoir. Signaling pathways Wnt, AMPK/mTOR and NF-κB are key determinants for TM cell generation, maintenance and proinflammatory effect. In this review, we focus on the phenotypic and functional characteristics of TSCM cells and discuss their role in autoimmune diseases and HIV-1 chronic infection. Also, we explore the potential mechanism and signaling pathways involved in immune memory and look into the future therapy strategies of targeting long-lived TM cells to suppress pathogenic immune memory.

The objective of this work was to develop nanomaterial inhibitor with long squeeze life for oil and gas production. Different surfactants, trisodium citrate (Na3Cit), cetyltrimethyl ammonium bromide (CTAB), benzethonium chloride (Hyamine), and bipyridinium dibromide (Gemini), were added to synthesize nanoparticle Ca-DTPMP inhibitor at pH 9.0. The inhibitors were characterized by scanning electron microscope (SEM) and dynamic light scattering (DLS). All these surfactants significantly decreased the particle size, but Gemini was the most effective one to control the calcium phosphonate salt particle size to be about 500 nm. Long-term squeeze experiments (~ 3,000 PV) saturated with calcite at 70 oC and 75 psi back pressure through a glass column packed with Fayetteville shale rock show that the return DTPMP concentration was as high as 3 ppm for the Gemini-Ca-DTPMP colloidal inhibitor. This is an unprecedented improvement in comparison to the squeeze return of DTPMP only inhibitor where the inhibitor return concentration dropped to below 1 ppm within 400 pore volumes. The Ca-DTPMP speciation, potential field application, and the SqueezeSoftPitzer model prediction, are also discussed.

The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests.We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE.We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016.Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort.Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.

Estimation distribution algorithm (EDA) is an evolution technique that uses sampling to generate the offspring. Most developed EDAs focus on solving the optimization problems which only have the constraints of variable boundaries. In this paper, EDAs are proposed for solving the constrained optimization problems (COPs) involving various types of constraints. In particular, a modified extreme elitism selection method is designed for EDAs to handle the constraints. This selection extrudes the role of some top best solutions to pull the mean vector of the Gaussian distribution towards these best solutions and makes EDAs form a primary evolutionary direction. The EDAs based on five different Gaussian distribution with this selection are evaluated using a set of benchmark functions and some engineering design problems. It is found that for solving these problems, the EDA that is based on a single multivariate Gaussian distribution model with the modified extreme elitism selection outperforms the other EDAs and some state-of-the-art techniques.

Recent high temperature H2S corrosion study reported that a thermodynamically less stable iron oxide layer can also form in addition to iron sulfide. In this work, H2S corrosion experiments were conducted at 120 °C for different exposure times, ranging from 1 to 21 days. The inner layer was identified by Transmission Electron Microscopy (TEM) as Fe3O4 (magnetite); Fe3O4 was always present over time despite it being less stable than iron sulfide. The observed formation sequence of iron sulfide at high temperature was mackinawite → troilite → pyrrhotite → pyrite. The role of the different corrosion product layers in corrosion is discussed.

Many studies have been reported that tripartite motif-containing (TRIM) proteins play important roles in various cellular processes and involved in many diseases. TRIM3, a member of TRIM family, has been proved that it plays important roles in various cancers. Nevertheless, its effects on cervical cancer reminded unknown. This study aimed to explore TRIM3 function in cervical cancer cells. The results of quantitative real-time RT-PCR and western blotting showed that the TRIM3 expression was very low in five cervical cancer cell lines. The TRIM3 overexpression weakened cell viability, and promote apoptosis of C-33A and SiHa cells in vitro, and inhibit tumor growth in vivo, which suggested that TRIM3 could reduce proliferation of cervical cancer cells. Moreover, TRIM3 up-regulation enhanced caspase-3 activity and increased the expressions of cleaved caspase-3 and p53, at the same time decreased p38 phosphorylation level. In addition, TRIM3 down-regulation had opposite effects on cell proliferation and expressions of the three proteins, which could be suppressed by p38-specific inhibitor (SB203580). In conclusion, TRIM3 had the ability to suppress cell proliferation by inactivating p38 signaling pathway, which indicated that it might act as a tumor inhibitor and an underlying therapeutic target for cervical cancer.

In this study, bortezomib (BTZ, a cytotoxic water-insoluble anticancer drug) was encapsulated in micellar nanoparticles having a catechol-functionalized polycarbonate core through a pH-sensitive covalent bond between phenylboronic acid (PBA) in BTZ and catechol, and these drug-loaded micelles were incorporated into hydrogels to form micelle/hydrogel composites. A series of injectable, biodegradable hydrogels with readily tunable mechanical properties were formed and optimized for sustained delivery of the BTZ-loaded micelles through ionic coacervation between PBA-functionalized polycarbonate/poly(ethylene glycol) (PEG) "ABA" triblock copolymer and a cationic one having guanidinium- or thiouronium-functionalized polycarbonate as "A" block. An in vitro release study showed the pH dependence in BTZ release. At pH 7.4, the BTZ release from the micelle/hydrogel composite remained low at 7%, whereas in an acidic environment, ∼85% of BTZ was released gradually over 9 days. In vivo studies performed in a multiple myeloma MM.1S xenograft mouse model showed that the tumor progression of mice treated with BTZ-loaded micelle solution was similar to that of the control group, whereas those treated with the BTZ-loaded micelle/hydrogel composite resulted in significant delay in the tumor progression. The results demonstrate that this hydrogel has great potential for use in subcutaneous and sustained delivery of drug-loaded micelles with superior therapeutic efficacy.

Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments. Importantly, high in vivo treatment efficacy of the macromolecules is achieved in MDR A. baumannii-, E. coli-, K. pneumoniae-, methicillin-resistant S. aureus-, cecal ligation and puncture-induced polymicrobial peritonitis, and P. aeruginosa lung infection mouse models while remaining non-toxic (e.g., therapeutic index—ED50/LD50: 1473 for A. baumannii infection). These biodegradable synthetic macromolecules have been demonstrated to have broad spectrum in vivo antimicrobial activity, and have excellent potential as systemic antimicrobials against MDR infections., Antibiotic resistance is a major threat across the whole healthcare spectrum. Here, the authors report on the development of biodegradable guanidinium functionalized polycarbonates and demonstrate antimicrobial activity against drug resistant infections.