Cervical Septum Incision Adversely Impacts Clinical Outcomes in Women with Complete Uterine Septum and Duplicated Cervix.

STUDY OBJECTIVE: To investigate the reproductive outcomes of women with complete septate uterus and duplicated cervix who either did or did not receive cervical septum incision during hysteroscopic transcervical incision of the uterine septum. DESIGN: Retrospective study approved by the hospital ethics committee. SETTING: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. PATIENTS: Women with complete septate uterus and duplicated cervix who underwent hysteroscopic transcervical incision of the uterine septum in Obstetrics and Gynecology Hospital of Fudan University between January 2008 and December 2020 (n = 105). INTERVENTIONS: Hysteroscopic incision of the septum. MEASUREMENTS AND MAIN RESULTS: Included patients were grouped according to whether or not cervical septum incision was performed. Reproductive outcomes including gravidity, abortion rate, preterm birth rate, full-term birth rate, premature rupture of membranes, and cervical incompetence were assessed. In the no incision group, the abortion rate (7.4%) was significantly lower than that of the incision group (27.6%, p = .01); the preterm birth rate (4.6%) was significantly lower than that of the incision group (36.8%); and the full-term birth rate (95.5%) exceeded that of the incision group (63.2%, p <.01). Incidence of premature rupture of membranes and cervical incompetence during pregnancy was higher in the incision group (15.8% and 10.5%, p <.01 and p = .03). CONCLUSION: Significantly improved reproductive outcomes were observed among patients with complete septate uterus and duplicated cervix whose cervical septum was preserved during the hysteroscopic transcervical incision of the uterine septum procedure.

Self-Promoted Hydroxyl Radical Releasing Magnetic Zn@Fe Particles.

Semiconductor photocatalysts, such as TiO2 and ZnO, have garnered significant attention for their ability to generate hydroxyl radicals, offering various practical applications. However, the reliance on UV light to facilitate electron-hole separation for hydroxyl radical production poses limitations. In this study, a novel approach is presented utilizing Zn@Fe core/shell particles capable of generating hydroxyl radicals without external energy input. The generation process involves electron donation from Zn to O2 , resulting in the formation of radical species . O2 - /H2 O2 , followed by Fe-catalyzed conversion of H2 O2 into hydroxyl radicals through the Fenton reaction. The release of . OH imparts good antimicrobial and antiviral properties to the Zn@Fe particles. Furthermore, the inclusion of Fe confers magnetic properties to the material. This dual functionality holds promise for diverse potential applications for the Zn@Fe particles.

Injectable Hydrogels Prepared Using Novel Synthetic Short Peptides with Defined Structure and Gelatin as Scaffolds to Support Cell and Tissue Growth.

Animal-derived basement-membrane matrices such as Geltrex are used to grow cells and tissues. Particularly, these are commonly applied to support tumor growth in animals for cancer research. However, a material derived from an animal source has an undefined composition, and may thus have unavoidable batch-to-batch variation in properties. To overcome these issues, a series of synthetic short peptides to form hydrogels is designed in combination with gelatin to promote cell adhesion and growth. The peptides have sequences of (X1Y1X2Y2)2 , where X1 and X2 are hydrophobic residues, while Y1 and Y2 are hydrophilic residues. The peptides spontaneously fold and self-assemble into a ß-sheet secondary structure upon contact with salts, and then aggregate to form hydrophilic networks of hydrogels. Hybrid hydrogels formed by mixing the peptide IEVEIRVK (IVK8) with gelatin are injectable and enzymatically degradable. The hybrid hydrogels at optimal compositions support SW480 and HepG2 tumor spheroid growth in vitro as effectively as Geltrex. More importantly, the peptide/gelatin hydrogels support tumor growth in a SW480 human colorectal adenocarcinoma xenograft mouse model. Altogether, the results illustrate that the synthetic peptide/gelatin hybrid hydrogel is a promising scaffold that can be used to support cell and tissue growth both in vitro and in vivo.

Redox Active Zn@MOFs as Spontaneous Reactive Oxygen Species Releasing Antimicrobials.

The rapid development of antimicrobial resistance (AMR) among infectious pathogens has become a major threat and challenge in healthcare systems globally. A strategy distinct from minimizing the overuse of antimicrobials involves the development of novel antimicrobials with a mode of action that prevents the development of AMR microbial strains. Reactive oxygen species (ROS) are formed as a natural byproduct of the cellular aerobic metabolism. However, it becomes pathological when ROS is produced at excessive levels. Exploiting this phenomenon, research on redox-active bactericides has been demonstrated to be beneficial. Materials that release ROS via photodynamic, thermodynamic, and photocatalytic interventions have been developed as nanomedicines and are used in various applications. However, these materials require external stimuli for ROS release to be effective as biocides. In this paper, we report novel zinc-based metal organic framework (Zn@MOF) particles that promote the spontaneous release of active ROS species. The synthesized Zn@MOF spontaneously releases superoxide anions and hydrogen peroxide, exhibiting a potent antimicrobial efficacy against various microbes. Zn@MOF-incorporated plastic films and coatings show excellent, long-lasting antimicrobial potency even under continuous microbial challenge and an aging process. These disinfecting surfaces maintain their antimicrobial properties even after 500× surface wipes. Zn@MOF is also biocompatible and safe on the skin, illustrating its broad potential applications in medical technology and consumer care applications.

A Self-Immolative DNA Nanogel Vaccine toward Cancer Immunotherapy.

The development of precisely engineered vehicles for intracellular delivery and the controlled release of payloads remains a challenge. DNA-based nanomaterials offer a promising solution based on the A-T-G-C alphabet-dictated predictable assembly and high programmability. Herein, we present a self-immolative DNA nanogel vaccine, which can be tracelessly released in the intracellular compartments and activate the immune response. Three building blocks with cytosine-rich overhang domains are designed to self-assemble into a DNA nanogel framework with a controlled size. Two oligo agonists and one antigen peptide are conjugated to the building blocks via an acid-labile chemical linker. Upon internalization into acidic endosomes, the formation of i-motif configurations leads to dissociation of the DNA nanogel vaccine. The acid-labile chemical linker is cleaved, releasing the agonists and antigen in their traceless original form to activate antigen-presenting cells and an immune response. This study presents a novel strategy for constructing delivery platforms for intracellularly stimuli-triggered traceless release of therapeutics.

Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study.

This study aims to investigate the influence of topical estrogen management in postmenopausal patients who had undergone CO2 laser ablation for vaginal squamous intraepithelial lesions (SILs). The clinical data of 211 postmenopausal women with vaginal SILs were reviewed. Patients were divided into two groups by 2-month different management: Group 1 (intervention group): patients were treated with estrogen cream 0.5 g every other day and Group 2 (control group): no topical agent was used for the treatment of patients. In low-grade squamous intraepithelial lesions (LSILs), the response rates for patients in the intervention group and the control group were 49.1% (27/55) and 54.2% (16/48), respectively; human papillomavirus (HPV) status turned negative in 12 (12/38, 31.6%) patients of the intervention group and in 15 (15/35, 42.9%) patients of the control group. In high-grade squamous intraepithelial lesions (HSILs), the response rates for patients in the intervention group and the control group were 72.4% (42/58) and 78.0% (39/50), respectively, nearly 1.5 times higher than those of the LSIL patients; 22 (22/54, 40.7%) patients of the intervention groups and 12 (12/46, 26.1%) patients of the control group cleared the HPV infection. In postmenopausal patients, local use of estrogen cream improves the recognition of lesions and is conducive to precision medicine.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IB3 and IIA2): study protocol of the LAUNCH 3 trial.

BACKGROUND: Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. METHODS/DESIGN: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. DISCUSSION: The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04939831 , retrospectively registered on 25 June 2021.

Lactate-mediated Fascin protrusions promote cell adhesion and migration in cervical cancer.

Background: Lactate is associated with the poor prognosis of many human malignancies. Cervical cancer, one of main causes of women mortality worldwide, is aggressive and absent of effective pharmacological treatment, and its underlying mechanisms of progression remain elusive. Methods: The regulation of ß-catenin to fascin protrusion formation upon acidic lactate (Lactic acid [LA]) stimulation was evaluated through in ß-catenin or fascin deficiency cell line models by immunofluorescence assays, and subcellular fractionation. The effect of ß-catenin and fascin relocation by LA and its antagonist were evaluated by immunohistochemistry assay in patient tissues and mouse tumor xenograft model. Trypsin digestion, Transwell assay, cell proliferation in vitro was performed to explore the role of LA in the cell growth, adhesion and migration. Results: Low concentration of LA significantly promotes cytoskeleton remodeling via `protrusion formation to increase cell adhesion and migration. Mechanistically, upon LA stimulation, ß-catenin diffuses from the cytoplasmic membrane into the nucleus, which in turn induces fascin nuclear-cytoplasm redistribution to the protrusion compartment. Moreover, the antagonist of LA sufficiently blocks the LA-mediated ß-catenin nuclear import, fascin nuclear export, and the growth and invasion of cervical cancer cells in vitro and in vivo using a murine xenograft model. Conclusions: This study uncovers ß-catenin-fascin axis as a key signal in response to extracellular lactate and indicates that antagonist of LA may serve as a potential clinical intervention for cancer development.

Hysteroscopic Fenestration with Precise Incision of the Cavity Septum: A Novel Minimally Invasive Surgery of Complete Septate Uterus with Double Cervix.

STUDY OBJECTIVE: This study aimed to develop and describe a novel surgical procedure that involves hysteroscopic fenestration with precise incision of the complete uterine septum and double cervix preservation after magnetic resonance imaging (MRI) evaluation in patients and to evaluate its efficacy. DESIGN: A prospective consecutive clinical study. SETTING: A university teaching hospital. PATIENTS: Twenty-four patients with complete septate uterus and double cervix. INTERVENTIONS: Three-dimensional reconstruction of uterus was performed with pelvic MRI and three-dimensional SPACE sequence scanning. Hysteroscopic fenestration with precise incision of the cavity septum and double cervix preservation was performed in patients. Three months after operation, follow-up pelvic MRI and second-look hysteroscopy were performed conventionally. MEASUREMENTS AND MAIN RESULTS: Operating time, blood loss, operative complications, MRI and hysteroscopic changes of uterus, symptoms improvement, and reproductive outcomes were assessed. The surgery was successfully completed without any intraoperative complications in all patients. Operating time was 21.71 ± 8.28 minutes (range, 10-40 minutes) and blood loss was 9.92 ± 7.14 mL (range, 5-30 mL). Postoperative MRI showed the uterine anteroposterior diameter (3.66 cm vs 3.92 cm; p <.05) was increased. Postoperative MRI and the second-look hysteroscopy showed the cavity shape and uterine volume were expanded to the normal. Symptoms of dysmenorrhea, abnormal uterine bleeding, and dyspareunia were ameliorated after the surgery in 70% of patients (7 of 10), 60% of patients (3 of 5), and 1 patient, respectively. The preoperative spontaneous abortion rate was 80% (4 of 5) and the postoperative spontaneous abortion rate was 11.11% (1 of 9). After the surgery, there were 2 ongoing pregnancies and 6 pregnancies ended in term births. Two live births were delivered by cesarean section and 4 by vaginal delivery without cervical incompetence during pregnancy. CONCLUSIONS: Hysteroscopic fenestration with precise incision of the uterine septum and double cervix preservation is an effective surgical procedure.

Vaginal Microbiome Dysbiosis is Associated with the Different Cervical Disease Status.

Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL, n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing. Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease. High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella, Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.

Altered vaginal eukaryotic virome is associated with different cervical disease status.

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.

A multicenter non-inferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stages IB1, IB2, and IIA1): study protocol of the LAUNCH 2 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early-stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology; therefore, this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB1, IB2, and IIA1) patient survival under stringent operation standards and consistent surgical oncologic principles. METHODS/DESIGN: This is an investigator-initiated, Prospective, Randomized, Open, Blinded End-point (PROBE)-controlled non-inferiority trial. A total of 780 patients with stage IB1, IB2, and IIA1 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary endpoint will be 5-year progression-free survival, and secondary endpoints include 5-year overall survival, recurrence, and quality of life measurements. DISCUSSION: The debate on laparoscopic versus abdominal RH is still ongoing, and high-quality evidences are needed to guide clinical practice. The study results will provide more convincing evidence-based information for early-stage cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov NCT04929769 . Registered on 18 June 2021.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. METHODS: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. DISCUSSION: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).

Acid-Resistant and Physiological pH-Responsive DNA Hydrogel Composed of A-Motif and i-Motif toward Oral Insulin Delivery.

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 via free-radical polymerization. In an acidic environment (pH 1.2-6.0), the generated copolymers form a hydrogel state, which is cross-linked by parallel A-motif duplex configurations (pH 1.2-3.0) and quadruplex i-motif structures (pH 4.0-6.0) due to the protonation of A and C bases, respectively. Specifically, the protonated A-rich sequences under pH 1.2-3.0 form a stable parallel A-motif duplex cross-linking unit through reverse Hoogsteen interaction and electrostatic attraction. Hemi-protonated C bases under mildly acidic pH (4.0-6.0) form quadruplex i-motif cross-linking configuration via Hoogsteen interaction. Under physiological pH, both A and C bases deprotonated, resulting in the separation of A-motif and i-motif to A-rich and C-rich single strands, respectively, and thereby the dissociation of the DNA hydrogel into the solution state. The acid-resistant and physiological pH-responsive DNA hydrogel was further developed for oral drug delivery to the hostile acidic environment in the stomach (pH 1.2), duodenum (pH 5.0), and small intestine (pH 7.2), where the drug would be released and absorbed. As a proof of concept, insulin was encapsulated in the DNA hydrogel and orally administered to diabetic rats. In vitro and in vivo studies demonstrated the potential usage of the DNA hydrogel for oral drug delivery.

PCAT6 May Be a Whistler and Checkpoint Target for Precision Therapy in Human Cancers.

LncRNAs are involved in the occurrence and progressions of multiple cancers. Emerging evidence has shown that PCAT6, a newly discovered carcinogenic lncRNA, is abnormally elevated in various human malignant tumors. Until now, PCAT6 has been found to sponge various miRNAs to activate the signaling pathways, which further affects tumor cell proliferation, migration, invasion, cycle, apoptosis, radioresistance, and chemoresistance. Moreover, PCAT6 has been shown to exert biological functions beyond ceRNAs. In this review, we summarize the biological characteristics of PCAT6 in a variety of human malignancies and describe the biological mechanisms by which PCAT6 can facilitate tumor progression. Finally, we discuss its diagnostic and prognostic values and clinical applications in various human malignancies.

Optimizing the Detection of Occult Cervical Cancer: A Prospective Multicentre Study in China.

PURPOSE: 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.

Decidual Natural Killer Cells: A Good Nanny at the Maternal-Fetal Interface During Early Pregnancy.

Decidual natural killer (dNK) cells are the tissue-resident and major subpopulation of NK cells at the maternal-fetal interface. It has been demonstrated that dNK cells play pivotal roles in pregnancy, including keeping maternal-fetal immune tolerance, promoting extravillous trophoblast (EVT) cell invasion, and driving uterine spiral artery remodeling. However, the molecular mechanisms haven't been elucidated until recent years. In this review, we systemically introduce the generation, subsets, and surface or soluble molecules of dNK cells, which are critical for maintaining the functions of dNK cells. Further, new functions of dNK cells including well-controlled cytotoxicity, immunosurveillance and immunotrophism supporting via the cell-cell interaction between dNK cells and EVT cells are mainly focused. The molecular mechanisms involved in these functions are also illustrated. Moreover, pregnancy-associated diseases caused by the dNK cells abnormalities are discussed. It will be important for future investigations about the mechanism of maintenance of pregnancy and parturition and potential clinical applications of dNK cells.

Stem cell-like memory T cells: A perspective from the dark side.

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.

Identification of differentially expressed proteins and clinicopathological significance of HMGB2 in cervical cancer.

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.

Evaluation of the ZnO Nanopillar Surface for Disinfection Applications.

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 in vivo. These findings illustrate the broad applicability of ZnO nanopillar surfaces in the common equipment used in health-care and consumer industries.