TMEM215 Prevents Endothelial Cell Apoptosis in Vessel Regression by Blunting BIK-Regulated ER-to-Mitochondrial Ca Influx.

BACKGROUND: In developmental and pathological tissues, nascent vessel networks generated by angiogenesis require further pruning/regression to delete nonfunctional endothelial cells (ECs) by apoptosis and migration. Mechanisms underlying EC apoptosis during vessel pruning remain elusive. TMEM215 (transmembrane protein 215) is an endoplasmic reticulum-located, 2-pass transmembrane protein. We have previously demonstrated that TMEM215 knockdown in ECs leads to cell death, but its physiological function and mechanism are unclear. METHODS: We characterized the role and mechanism of TMEM215 in EC apoptosis using human umbilical vein endothelial cells by identifying its interacting proteins with immunoprecipitation-mass spectrometry. The physiological function of TMEM215 in ECs was assessed by establishing a conditional knockout mouse strain. The role of TMEM215 in pathological angiogenesis was evaluated by tumor and choroidal neovascularization models. We also tried to evaluate its translational value by delivering a Tmem215 small interfering RNA (siRNA) using nanoparticles in vivo. RESULTS: TMEM215 knockdown in ECs induced apoptotic cell death. We identified the chaperone BiP as a binding partner of TMEM215, and TMEM215 forms a complex with and facilitates the interaction of BiP (binding immunoglobin protein) with the BH (BCL-2 [B-cell lymphoma 2] homology) 3-only proapoptotic protein BIK (BCL-2 interacting killer). TMEM215 knockdown triggered apoptosis in a BIK-dependent way and was abrogated by BCL-2. Notably, TMEM215 knockdown increased the number and diminished the distance of mitochondria-associated endoplasmic reticulum membranes and increased mitochondrial calcium influx. Inhibiting mitochondrial calcium influx by blocking the IP3R (inositol 1,4,5-trisphosphate receptor) or MCU (mitochondrial calcium uniporter) abrogated TMEM215 knockdown-induced apoptosis. TMEM215 expression in ECs was induced by physiological laminar shear stress via EZH2 downregulation. In EC-specific Tmem215 knockout mice, induced Tmem215 depletion impaired the regression of retinal vasculature characterized by reduced vessel density, increased empty basement membrane sleeves, and increased EC apoptosis. Moreover, EC-specific Tmem215 ablation inhibited tumor growth with disrupted vasculature. However, Tmem215 ablation in adult mice attenuated lung metastasis, consistent with reduced Vcam1 expression. Administration of nanoparticles carrying Tmem215 siRNA also inhibited tumor growth and choroidal neovascularization injury. CONCLUSIONS: TMEM215, which is induced by blood flow-derived shear stress via downregulating EZH2, protects ECs from BIK-triggered mitochondrial apoptosis mediated by calcium influx through mitochondria-associated ER membranes during vessel pruning, thus providing a novel target for antiangiogenic therapy.

Redox Activity of Co Species in the Active Sites of CoN x /CoO x Facilitates Oxygen Electrocatalysis for Zn-Air Batteries.

Developing efficient bifunctional oxygen electrocatalysts is crucial for enhancing the performance of rechargeable Zn-air batteries (ZABs). In this study, cobalt/cobalt oxides embedded in N-doped carbon nanofibers (Co/CoOx/NCNFs) were synthesized through a combination of electrospinning and annealing processes. The resulting Co/CoOx/NCNFs catalysts feature abundant CoNx and CoOx active species, leveraging the large specific surface area of nanofibers to facilitate oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The optimized Co/CoOx/NCNFs-0.1 achieved a half-wave potential (vs. RHE) of 0.82 V and required only 429 mV to reach 10 mA cm⁻² in a typical three-electrode system with 0.1 M KOH using an electrochemical workstation equipped with a pine instruments rotator, outperforming the Pt/C+RuO2. The assembled ZABs exhibited high specific capacity (771 mAh gZn-1), substantial power density (981.6 mWh gZn-1), and long-term stability (>325 h). In situ Raman spectroscopy confirmed that the electrocatalytic processes involve the redox activity of Co (II and III) species derived from abundant CoNx and CoOx, elaborating the origin of the catalysts' exceptional oxygen electrocatalysis performance. This work not only presents a straightforward and effective approach for producing bifunctional oxygen electrocatalysts in ZABs but also sheds light on the catalytic mechanisms underlying ORR and OER for CoNx/CoOx-based oxygen electrocatalysts.

Self-Organized Spatiotemporal Mineralization of Hydrogel: A Simulant of Osteon.

Nature creates fascinating self-organized spatiotemporal patterns through the delicate control of reaction-diffusion dynamics. As the primary unit of cortical bone, osteon has concentric lamellar architecture, which plays a crucial role in the mechanical and physiological functions of bone. However, it remains a great challenge to fabricate the osteon-like structure in a natural self-organization way. Taking advantage of the nonequilibrium reaction in hydrogels, a simple mineralization strategy to closely mimic the formation of osteon in a mild physiological condition is developed. By constructing two reverse concentration gradients of ions from periphery to interior of cylindrical hydrogel, spatiotemporal self-organization of calcium phosphate in concentric rings is generated. It is noteworthy that minerals in different layers possess diverse contents and crystalline phases, which further guide the adhesion and spread of osteoblasts on these patterns, resembling the architecture and cytological behavior of osteon. Besides, theoretical data indicates the predominate role of ion concentrations and pH values of solution, in good accordance with experimental results. Independent of precise instruments, this lifelike method is easily obtained, cost-efficient, and effectively imitates the mineral deposition in osteon from a physiochemical view. The strategy may be expanded to develop other functional material patterns via spatiotemporal self-organization.

Clinical significance of umbilical artery intermittent vs persistent absent end-diastolic velocity in growth-restricted fetuses.

BACKGROUND: Umbilical artery absent end-diastolic velocity indicates increased placental resistance and is associated with increased risk of perinatal demise and neonatal morbidity in fetal growth restriction. However, the clinical implications of intermittent vs persistent absent end-diastolic velocity are unclear. OBJECTIVE: We compared umbilical artery Doppler velocimetry changes during pregnancy and neonatal outcomes between pregnancies with fetal growth restriction and intermittent absent end-diastolic velocity and those with persistent absent end-diastolic velocity. STUDY DESIGN: In this retrospective study of singletons with fetal growth restriction and absent end-diastolic velocity, umbilical artery Doppler abnormalities were classified as follows: intermittent absent end-diastolic velocity (<50% of cardiac cycles with absent end-diastolic velocity) and persistent absent end-diastolic velocity (≥50% of cardiac cycles with absent end-diastolic velocity). The primary outcome was umbilical artery Doppler progression to reversed end-diastolic velocity. Secondary outcomes included sustained umbilical artery Doppler improvement, latency to delivery, gestational age at delivery, neonatal morbidity composite, rates of neonatal intensive care unit admission, and length of neonatal intensive care unit stay. Outcomes were compared between intermittent absent end-diastolic velocity and persistent absent end-diastolic velocity. Multivariate logistic regression was used to adjust for confounders. A receiver operating characteristic curve was generated to assess the sensitivity and specificity of the percentage of waveforms with absent end-diastolic velocity in predicting the neonatal composite. The Youden index was used to calculate the optimal absent end-diastolic velocity percentage cut-point for predicting the neonatal composite. RESULTS: Of the 77 patients included, 38 had intermittent absent end-diastolic velocity and 39 had persistent absent end-diastolic velocity. Maternal characteristics, including age, parity, and preexisting conditions did not differ significantly between the 2 groups. Progression to reversed end-diastolic velocity was less common in intermittent absent end-diastolic velocity than in persistent absent end-diastolic velocity (7.9% vs 25.6%; odds ratio, 0.25; 95% confidence interval, 0.06-0.99). Sustained umbilical artery Doppler improvement was more common in intermittent absent end-diastolic velocity than in persistent absent end-diastolic velocity (50.0% vs 10.3%; odds ratio, 8.75; 95% confidence interval, 2.60-29.5). Pregnancies with intermittent absent end-diastolic velocity had longer latency to delivery than those with persistent absent end-diastolic velocity (11 vs 3 days; P<.01), and later gestational age at delivery (33.9 vs 28.7 weeks; P<.01). Composite neonatal morbidity was less common in the intermittent absent end-diastolic velocity group (55.3% vs 92.3%; P<.01). Neonatal death occurred in 7.9% of intermittent absent end-diastolic velocity cases and 33.3% of persistent absent end-diastolic velocity cases (P<.01). The differences in neonatal outcomes were no longer significant when controlling for gestational age at delivery. The percentage of cardiac cycles with absent end-diastolic velocity was a modest predictor of neonatal morbidity, with an area under the receiver operating characteristic curve of 0.71 (95% confidence interval, 0.58-0.84). The optimal percentage cut-point for fetal cardiac cycles with absent end-diastolic velocity observed at the sentinel ultrasound for predicting neonatal morbidity was calculated to be 47.7%, with a sensitivity of 65% and specificity of 85%. CONCLUSIONS: Compared with persistent absent end-diastolic velocity, diagnosis of intermittent absent end-diastolic velocity in the setting of fetal growth restriction is associated with lower rates of progression to reversed end-diastolic velocity, higher likelihood of umbilical artery Doppler improvement, longer latency to delivery, and higher gestational age at delivery, leading to lower rates of neonatal morbidity and death. Our data support using an absent end-diastolic velocity percentage cut-point in 50% of cardiac cycles to differentiate intermittent absent end-diastolic velocity from persistent absent end-diastolic velocity. This differentiation in growth-restricted fetuses with absent end-diastolic velocity may allow further risk stratification.

Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma-specific survival.

A few single-nucleotide polymorphisms (SNPs) have been identified to be associated with cutaneous melanoma (CM) survival through genome-wide association studies, but stringent multiple testing corrections required for the hypothesis-free testing may have masked some true associations. Using a hypothesis-driven analysis approach, we sought to evaluate associations between SNPs in ketone body metabolic pathway genes and CM survival. We comprehensively assessed associations between 4196 (538 genotyped and 3658 imputed) common SNPs in 44 ketone body metabolic pathway genes and CM survival, using a dataset of 858 patients of a case-control study from The University of Texas M.D. Anderson Cancer Center as the discovery set and another dataset of 409 patients from the Nurses' Health Study and the Health Professionals Follow-up Study as the replication set. There were 95/858 (11.1%) and 48/409 (11.7%) patients who died of CM, respectively. We identified two independent SNPs (ie, PDSS1 rs12254548 G>C and SLC16A6 rs71387392 G>A) that were associated with CM survival, with allelic hazards ratios of 0.58 (95% confidence interval [CI] = 0.44-0.76, P = 9.00 × 10-5 ) and 1.98 (95% CI = 1.34-2.94, P = 6.30 × 10-4 ), respectively. Additionally, associations between genotypes of the SNPs and messenger RNA expression levels of their corresponding genes support the biologic plausibility of a role for these two variants in CM tumor progression and survival. Once validated by other larger studies, PDSS1 rs12254548 and SLC16A6 rs71387392 may be valuable biomarkers for CM survival.

Fabrication of Double-Network Hydrogels with Universal Adhesion and Superior Extensibility and Cytocompatibility by One-Pot Method.

Hydrogels, which demand simultaneously tailorable mechanical properties and excellent biocompatibility, act as a promoting material for biomedical applications, e.g., tissue engineering scaffolds, wound dressing materials, and cartilage substitutes. Double-network hydrogels (DN hydrogels) have attracted widespread concerns due to their extraordinary mechanical strength and toughness, while traditional DN hydrogels are limited in terms of their biofunctionality. Based on the DN hydrogels composed of agar and acrylamide (AM), we incorporate vinylphosphoric acid (VPA) into the network to obtain agar/PAM/PVPA hydrogels with universal adhesion and superior cytocompatibility. Meanwhile, the agar/PAM/PVPA hydrogel maintains its high strength and toughness. It is noted that the elongation of the agar/PAM/PVPA hydrogel (molar ratio of VPA is 2%) is up to 3418.9 ± 54.9%. The cell experiment also demonstrates that the addition of VPA in a proper concentration can promote cell adhesion and proliferation. Furthermore, the hydrogel has the potential to be used as 3D printing and injectable materials because of the thermoreversible sol-gel agar. The reported agar/PAM/PVPA hydrogel in this work with universal adhesion, excellent mechanical properties, and excellent cytocompatibility is able to be used for biomedical applications as scaffolds, wound dressing materials, or cartilage repair materials.

Genetic variants in ELOVL2 and HSD17B12 predict melanoma-specific survival.

Fatty acids play a key role in cellular bioenergetics, membrane biosynthesis and intracellular signaling processes and thus may be involved in cancer development and progression. In the present study, we comprehensively assessed associations of 14,522 common single-nucleotide polymorphisms (SNPs) in 149 genes of the fatty-acid synthesis pathway with cutaneous melanoma disease-specific survival (CMSS). The dataset of 858 cutaneous melanoma (CM) patients from a published genome-wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used as the discovery dataset, and the identified significant SNPs were validated by a dataset of 409 CM patients from another GWAS from the Nurses' Health and Health Professionals Follow-up Studies. We found 40 noteworthy SNPs to be associated with CMSS in both discovery and validation datasets after multiple comparison correction by the false positive report probability method, because more than 85% of the SNPs were imputed. By performing functional prediction, linkage disequilibrium analysis, and stepwise Cox regression selection, we identified two independent SNPs of ELOVL2 rs3734398 T>C and HSD17B12 rs11037684 A>G that predicted CMSS, with an allelic hazards ratio of 0.66 (95% confidence interval = 0.51-0.84 and p = 8.34 × 10-4 ) and 2.29 (1.55-3.39 and p = 3.61 × 10-5 ), respectively. Finally, the ELOVL2 rs3734398 variant CC genotype was found to be associated with a significantly increased mRNA expression level. These SNPs may be potential markers for CM prognosis, if validated by additional larger and mechanistic studies.

Three novel genetic variants in NRF2 signaling pathway genes are associated with pancreatic cancer risk.

Pancreatic cancer (PanC) is one of the most lethal solid malignancies, and metastatic PanC is often present at the time of diagnosis. Although several high- and low-penetrance genes have been implicated in PanC, their roles in carcinogenesis remain only partially elucidated. Because the nuclear factor erythroid2-related factor2 (NRF2) signaling pathway is involved in human cancers, we hypothesize that genetic variants in NRF2 pathway genes are associated with PanC risk. To test this hypothesis, we assessed associations between 31 583 common single nucleotide polymorphisms (SNP) in 164 NRF2-related genes and PanC risk using three published genome-wide association study (GWAS) datasets, which included 8474 cases and 6944 controls of European descent. We also carried out expression quantitative trait loci (eQTL) analysis to assess the genotype-phenotype correlation of the identified significant SNP using publicly available data in the 1000 Genomes Project. We found that three novel SNP (ie, rs3124761, rs17458086 and rs1630747) were significantly associated with PanC risk (P = 5.17 × 10-7 , 5.61 × 10-4 and 5.52 × 10-4 , respectively). Combined analysis using the number of unfavorable genotypes (NUG) of these three SNP suggested that carriers of two to three NUG had an increased risk of PanC (P < 0.0001), compared with those carrying zero to one NUG. Furthermore, eQTL analysis showed that both rs3124761 T and rs17458086 C alleles were associated with increased mRNA expression levels of SLC2A6 and SLC2A13, respectively (P < 0.05). In conclusion, genetic variants in NRF2 pathway genes could play a role in susceptibility to PanC, and further functional exploration of the underlying molecular mechanisms is warranted.

Zwitterionic PMCP-Modified Polycaprolactone Surface for Tissue Engineering: Antifouling, Cell Adhesion Promotion, and Osteogenic Differentiation Properties.

Biodegradable polycaprolactone (PCL) has been widely applied as a scaffold material in tissue engineering. However, the PCL surface is hydrophobic and adsorbs nonspecific proteins. Some traditional antifouling modifications using hydrophilic moieties have been successful but inhibit cell adhesion, which is not ideal for tissue engineering. The PCL surface is modified with bioinspired zwitterionic poly[2-(methacryloyloxy)ethyl choline phosphate] (PMCP) via surface-initiated atom transfer radical polymerization to improve cell adhesion through the unique interaction between choline phosphate (CP, on PMCP) and phosphate choline (PC, on cell membranes). The hydrophilicity of the PCL surface is significantly enhanced after surface modification. The PCL-PMCP surface reduces nonspecific protein adsorption (e.g., up to 91.7% for bovine serum albumin) due to the zwitterionic property of PMCP. The adhesion and proliferation of bone marrow mesenchymal stem cells on the modified surface is remarkably improved, and osteogenic differentiation signs are detected, even without adding any osteogenesis-inducing supplements. Moreover, the PCL-PMCP films are more stable at the early stage of degradation. Therefore, the PMCP-functionalized PCL surface promotes cell adhesion and osteogenic differentiation, with an antifouling background, and exhibits great potential in tissue engineering.

Genetic variants in the liver kinase B1-AMP-activated protein kinase pathway genes and pancreatic cancer risk.

The liver kinase B1-AMP-activated protein kinase (LKB1-AMPK) pathway has been identified as a new target for cancer therapy, because it controls the glucose and lipid metabolism in response to alterations in nutrients and intracellular energy levels. In the present study, we aimed to identify genetic variants of the LKB1-AMPK pathway genes and their associations with pancreatic cancer (PanC) risk using 15 418 participants of European ancestry from two previously published PanC genome-wide association studies. We found that six novel tagging single-nucleotide polymorphisms (SNPs) (i.e, MAP2 rs35075084 T > deletion, PRKAG2 rs2727572 C > T and rs34852782 A > deletion, TP53 rs9895829 A > G, and RPTOR rs62068300 G > A and rs3751936 G > C) were significantly associated with an increased PanC risk. The multivariate logistic regression model incorporating the number of unfavorable genotypes (NUGs) with adjustment for age and sex showed that carriers with five to six NUGs had an increased PanC risk (odds ratio = 1.24, 95% confidence interval = 1.16-1.32 and P < 0.0001), compared to those with zero to four NUGs. Subsequent expression quantitative trait loci (eQTL) analysis further revealed that these SNPs were associated with significantly altered mRNA expression levels either in 373 normal lymphoblastoid cell lines (TP53 SNP rs9895829, P < 0.05) or in whole blood cells of 369 normal donors from the genotype-tissue expression project (GTEx) database [RPTOR SNP rs60268947 and rs28434589, both in high linkage disequilibrium (r2 > 0.9) withRPTOR rs62068300, P < 0.001]. Collectively, our findings suggest that these novel SNPs in the LKB1-AMPK pathway genes may modify susceptibility to PanC, possibly by influencing gene expression.

The chemical diversity and structure-based discovery of allosteric modulators for the PIF-pocket of protein kinase PDK1.

Phosphoinositide-dependent protein kinase-1 (PDK1) is an important protein in mediating the PI3K-AKT pathway and is thus identified as a promising target. The catalytic activity of PDK1 is tightly regulated by allosteric modulators, which bind to the PDK1 Interacting Fragment (PIF) pocket of the kinase domain that is topographically distinct from the orthosteric, ATP binding site. Allosteric modulators by attaching to the less conserved PIF-pocket have remarkable advantages such as higher selectivity, less side effect, and lower toxicity. Targeting allosteric PIF-pocket of PDK1 has become the focus of recent attention. In this review, we summarise the current advances in the structure-based discovery of PDK1 allosteric modulators. We will first present the three-dimensional structure of PDK1 and illustrate the allosteric regulatory mechanism of PDK1 through the modulation of the PIF-pocket. Then, the recent advances of PDK1 allosteric modulators targeting the PIF-pocket will be recapitulated detailly according to the structural similarity of allosteric modulators.

Multifunctional Biomaterial Coating Based on Bio-Inspired Polyphosphate and Lysozyme Supramolecular Nanofilm.

Current implant materials have widespread clinical applications together with some disadvantages, the majority of which are the ease with which infections are induced and difficulty in exhibiting biocompatibility. For the efficient improvement of their properties, the development of interface multifunctional modification in a simple, universal, and environmently benign approach becomes a critical challenge and has acquired the attention of numerous scientists. In this study, a lysozyme-polyphosphate composite coating was fabricated for titanium(Ti)-based biomaterial to obtain a multifunctional surface. This coating was easily formed by sequentially soaking the substrate in reduced-lysozyme and polyphosphate solution. Such a composite coating has shown predominant antibacterial activity against Gram-negative bacteria ( E. coli) and improved cell adhesion, proliferation, and differentiation, which are much better than those of the pure substrate. This facile modification endows the biomaterial with anti-infective and potential bone-regenerative performance for clinical applications of biomaterial implants.

NDRG2 overexpression suppresses hepatoma cells survival during metabolic stress through disturbing the activation of fatty acid oxidation.

Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation. Moreover, NDRG2 overexpression aggravated energy imbalance and oxidative stress by decreasing the intracellular ATP and NADPH generation and increasing ROS levels. Strikingly, NDRG2 inhibited the activation of fatty acid oxidation (FAO), which preserves ATP and NADPH purveyance in the absence of glucose. Finally, mechanistic investigation showed that NDRG2 overexpression suppressed the glucose-deprivation induced AMPK/ACC pathway activation in hepatoma cells, whereas the expression of a constitutively active form of AMPK abrogated glucose-deprivation induced AMPK activation and cell apoptosis. Thus, as a negative regulator of AMPK, NDRG2 disturbs the induction of FAO genes by glucose limitation, leading to dysregulation of ATP and NADPH, and thus reduces the tolerance of hepatoma cells to glucose limitation.

Functional and clinical evidence that TAZ is a candidate oncogene in hepatocellular carcinoma.

Transcriptional co-activator with PDZ-binding motif (TAZ) has been reported to be associated with carcinogenesis. However, the cellular function of TAZ in human hepatocellular carcinoma (HCC) remains elusive. In this study, an immunohistochemistry analysis revealed that the expression of TAZ in cancer tissue samples from 180 HCC patients was significantly higher than that in adjacent normal tissues. In addition, TAZ overexpression was significantly correlated with aggressive tumor characteristics such as tumor size, TNM stage, lymph node or distant metastasis, histological differentiation, and recurrent HCC (P < 0.05). The Kaplan-Meier test showed that TAZ-positive expression was related to a poor prognosis compared to TAZ-negative expression (P < 0.05). Furthermore, the expression level of TAZ was generally correlated with the invasiveness of cancer cells. The overexpression of TAZ in the Huh7 cell line, which endogenously expresses TAZ at low levels, significantly promoted cell proliferation, migration and invasion and inhibited apoptosis, whereas RNA interference-mediated knockdown of TAZ in the highly invasive cell line MHCC-97H significantly suppressed cell proliferation, migration and invasion in vitro and tumor formation in vivo.

Thymosin alpha 1 suppresses proliferation and induces apoptosis in breast cancer cells through PTEN-mediated inhibition of PI3K/Akt/mTOR signaling pathway.

Thymosin alpha 1 (Tα1), an immunoactive peptide, has been shown to inhibit cell proliferation and induce apoptosis in human leukemia, non-small cell lung cancer, melanoma, and other human cancers. However, the response and molecular mechanism of breast cancer cells exposed to Tα1 remain unclear. PTEN, a tumor suppressor gene, is frequently mutated in a variety of human cancers. In the present study, we aimed to investigate the biological roles of PTEN in the growth inhibition of human breast cancer cells exposed to Tα1. Using wild-type and mutant PTEN-expressing cells, we found a strong correlation between PTEN status and Tα1-mediated growth inhibition of breast cancer cells. The growth inhibition effect was more pronounced in breast cancer cells in which Tα1 enhanced PTEN expression, whereas endogenous PTEN knockdown reversed the growth inhibition effect of Tα1 in breast cancer cells. Further investigation revealed that PTEN up-regulation, which was induced by Tα1, can inhibit the activation of the PI3K/Akt/mTOR signaling pathway, leading to the growth inhibition of breast cancer cells. The addition of the synergy between Tα1 and the inhibition of PI3K/Akt/mTOR activation could strongly block cell viability in PTEN down-regulated breast cancer cells. PTEN-overexpressing cells not only up-regulated Bax and cleaved caspase-3/9 and PARP expression but also down-regulated Bcl-2 compared to the treatment with Tα1 alone. Together these findings suggest that PTEN mediates Tα1-induced apoptosis through the mitochondrial death cascade and inhibition of the PI3K/Akt/mTOR signaling pathway in breast cancer cells.

Histochemical analysis of testis specific gene 13 in human normal and malignant tissues.

Testis-specific gene 13 (TSGA13) is abundantly expressed in testis. As previous studies of TSGA13 expression pattern have all been based on mRNA analysis, it is imperative to investigate its actual protein expression. Here, we first examined TSGA13 gene tree and protein homology among species, and found that TSGA13 is relatively well conserved. Next, we detected its protein expression in normal human tissues as well as in a limited number of malignant tumors by immunohistochemistry (IHC). It was demonstrated that, in addition to testis, high expression of TSGA13 could also be observed in multiple normal tissues, including stomach, larynx, spleen, bladder, tonsil, liver and thyroid. Notably, most types of human carcinoma tissues displayed reduced expression of TSGA13 rather than their adjacent normal tissues except glioblastoma and lung cancer. Hence, the data from the current study strongly suggest the association between TSGA13 and tumor malignancy.

Electrospun Carvacrol-Loaded Polyacrylonitrile/Poly(ethylene oxide) Nanofibrous Films as Wound Dressings.

Preventing microbial infections and accelerating wound closure are essential in the process of wound healing. In this study, various concentrations of carvacrol (CA) were loaded into polyacrylonitrile/poly(ethylene oxide) (PAN/PEO) nanofiber membranes to develop potential wound dressing materials via an electrospinning technique. The morphology and structure of the PAN/PEO/CA nanofiber membrane were analyzed by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), respectively. Subsequently, antimicrobial performance testing showed that the PAN/PEO/CA nanofiber membrane exhibited antimicrobial activity in a concentration-dependent manner. Moreover, SEM and transmission electron microscopy revealed that the number of Staphylococcus aureus decreased significantly and the microstructure of the biofilm was seriously damaged. Next, compared with the control and PAN/PEO groups, the PAN/PEO/5% CA group in a full-thickness skin infection model not only exhibited reduced wound exudate on day 2 after infection but also displayed a greater ability to achieve complete skin regeneration, with faster wound healing. Finally, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the downregulated differentially expressed genes between PAN/PEO- and PAN/PEO/5% CA-treated S. aureus were enriched in the two-component system and S. aureus infection. In conclusion, the antimicrobial materials of PAN/PEO/CA inhibited microbial growth and promoted wound healing with potential applications in the clinical management of wounds.

Colloidal photonic crystals towards biological applications.

Colloidal photonic crystals (CPCs), fabricated from the assembly of micro-/nano-particles, have attracted considerable interest due to their unique properties, such as structural color, slow-photon effect, and high specific surface area (SSA). Benefiting from these properties, significant progress has been made in the biological applications of CPCs. In this perspective, these properties and relative manipulation strategies are firstly discussed, building bridges between properties and biological applications of CPCs. Structural color endows CPCs with naked-eye sensing capability, which can be applied to physiological state assessment and diagnosis, as well as self-report of CPC-based diagnostic and therapeutic devices. The slow-photon effect contributes to enhanced fluorescence, surface-enhanced Raman scattering, and efficacy of photodynamic/photothermal therapy, when CPCs are combined with corresponding functional materials. High SSA provides CPCs with abundant binding sites and superior capabilities for loading, adsorption, delivery, etc. These properties can be utilized individually or synergistically to grant CPCs superior performance in biological applications. Next, the recent advancements of CPCs towards biological applications are summarized, including biosensors, wound dressings, cells-on-a-chip, and phototherapy. Finally, a perspective on the challenges and future development of CPCs for biological applications is presented.

Bimetallic Organic Gel for Effective Methyl Orange Dye Adsorption.

A bimetallic organic gel (MOG-Fe/Al) was synthesized through the solvothermal method. The gel state of the product obtained under optimized gel formation conditions is sufficient to carry 2 g of weight for a long time. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) technique, and X-ray photoelectron spectroscopy (XPS) analysis confirmed the structures and morphologies of the synthesized materials. MOG-Fe/Al, with good stability, excellent durability, and wide applicability, exhibited efficient MO adsorption capacity as high as 335.88 mg/g at 25 °C. Adsorption-influencing factors including solution pH, contact time, and temperature were investigated. The adsorption performance of the bimetallic organic gel was better than that of the monometallic organic gels (MOG-Fe and MOG-Al), and its adsorption processes were in accordance with the pseudo-second-order kinetic and Langmuir isothermal models. The excellent adsorption capacity of the MOG-Fe/Al is due to its surface structure, pore volume, π-π interactions, hydrogen bonds, and electrostatic interactions.