Electrochemical monitoring of congo red degradation using strontium titanate-doped biochar nanohybrids derived photocatalytic plates.

Present investigation demonstrates the development and characterization of strontium titanate (SrTiO3) doped biochar nanohybrid photocatalysts. Biochar nanohybrid was synthesized using an ultrasonic-assisted dispersion technique, which involved dispersing SrTiO3 nanoparticles into activated biochar at a weight ratio of 1:2 (w/w) under ambient conditions. The development of the biochar nanohybrid was verified through a comprehensive analysis of their spectral, microstructural, thermal, electrical, and electrochemical properties. The scanning electron microscopy analysis reveals a surface-associated multiphase morphology of the biochar nanohybrid, attributed to the uniform distribution of SrTiO3 within the activated biochar matrix. Biochar nanohybrid exhibited a reduced optical band gap of 2.77 eV, accompanied by a crystallite size of 32.45. Thermogravimetric analysis revealed the thermal stability of the biochar nanohybrid, as evidenced by a char residue of 70.83% at 1000 °C. The working electrodes derived from biochar nanohybrid have exhibited ohmic behavior and displayed a significantly enhanced DC conductivity (mS/cm) of 1.13, surpassing that of activated biochar (0.53) and SrTiO3 (0.62) at 100 V. The developed biochar nanohybrid were employed for the degradation of congo red dye by exposing the dye solution to photocatalytic plates. These photocatalytic plates were prepared by coating biochar nanohybrid onto glass plates using epoxy-based reactive binders for secure binding. The photodegradation of congo red was evaluated through cyclic voltammetric analysis in a 0.1 M KCl solution at pH 8.0, resulting in an impressive 99.95% photocatalytic efficiency in degrading a congo red solution (50 mg/L). This study presents a novel approach for the fabrication of biochar nanohybrid-derived photocatalytic plates, offering high photocatalytic efficiency for the degradation of congo red dye.

Interferon-gamma signaling promotes melanoma progression and metastasis.

Interferon-gamma (IFNG) has long been regarded as the flag-bearer for the anti-cancer immunosurveillance mechanisms. However, relatively recent studies have suggested a dual role of IFNG, albeit there is no direct experimental evidence for its potential pro-tumor functions. Here we provide in vivo evidence that treatment of mouse melanoma cell lines with Ifng enhances their tumorigenicity and metastasis in lung colonization allograft assays performed in immunocompetent syngeneic host mice, but not in immunocompromised host mice. We also show that this enhancement is dependent on downstream signaling via Stat1 but not Stat3, suggesting an oncogenic function of Stat1 in melanoma. The experimental results suggest that melanoma cell-specific Ifng signaling modulates the tumor microenvironment and its pro-tumorigenic effects are partially dependent on the γδ T cells, as Ifng-enhanced tumorigenesis was inhibited in the TCR-δ knockout mice. Overall, these results show that Ifng signaling may have tumor-promoting effects in melanoma by modulating the immune cell composition of the tumor microenvironment.

Comparative e-waste plastics biodegradation efficacy of monoculture Pseudomonas aeruginosa strain PE10 and bacterial consortium under in situ condition.

A significant amount of electronic obsoletes or electronic waste (e-waste) is being generated globally each year; of these, ~20% of obsolete electronic items have plastic components. Current remediation practices for e-waste have several setbacks due to its negative impact on the environment, agro-ecosystem, and human health. Therefore, comparative biodegradation studies of e-waste plastics by monoculture Pseudomonas aeruginosa strain PE10 and bacterial consortium consisting of Achromobacter insolitus strain PE2 (MF943156), Acinetobacter nosocomialis strain PE5 (MF943157), Pseudomonas lalkuanensis PE8 (CP043311), and Stenotrophomonas pavanii strain PE15 (MF943160) were carried out in situ. Biological treatment of e-waste with these candidates in soil ecosystems has been analyzed through diversified analytical techniques such as Fourier transform infrared spectroscopy (FTIR), thermogravimetric-derivative thermogravimetry-differential thermal analysis (TG-DTG-DTA), and scanning electron microscopy (SEM). Both P. aeruginosa strain PE10 and the bacterial consortium have a tremendous ability to accelerate the biodegradation process in the natural environment. However, FTIR analysis implied that the monoculture had better efficacy than the consortium, and it was consistent until the incubation period used for the study. Some polymeric bonds such as ν C=C and δ C-H were completely removed, and ν C=C ring stretching, νasym C-O-C, νsym C-H, etc. were introduced by strain PE10. Furthermore, thermal analysis results validated the structural deterioration of e-waste as the treated samples showed nearly two-fold weight loss (WL; 6.8%) than the untreated control (3.1%) at comparatively lower temperatures. SEM images provided the details of surface disintegrations. Conclusively, individual monoculture P. aeruginosa strain PE10 could be explored for e-waste bio-recycling in agricultural soil ecosystems thereby reducing the cost, time, and management of bioformulation in addition to hazardous pollutant reduction.

Suppression of Ca2+ signaling enhances melanoma progression.

The role of store-operated Ca2+ entry (SOCE) in melanoma metastasis is highly controversial. To address this, we here examined UV-dependent metastasis, revealing a critical role for SOCE suppression in melanoma progression. UV-induced cholesterol biosynthesis was critical for UV-induced SOCE suppression and subsequent metastasis, although SOCE suppression alone was both necessary and sufficient for metastasis to occur. Further, SOCE suppression was responsible for UV-dependent differences in gene expression associated with both increased invasion and reduced glucose metabolism. Functional analyses further established that increased glucose uptake leads to a metabolic shift towards biosynthetic pathways critical for melanoma metastasis. Finally, examination of fresh surgically isolated human melanoma explants revealed cholesterol biosynthesis-dependent reduced SOCE. Invasiveness could be reversed with either cholesterol biosynthesis inhibitors or pharmacological SOCE potentiation. Collectively, we provide evidence that, contrary to current thinking, Ca2+ signals can block invasive behavior, and suppression of these signals promotes invasion and metastasis.

Gadd45 in Senescence.

Gadd45a, Gadd45b, and Gadd45g have been implicated in cell cycle arrest, DNA repair, apoptosis, innate immunity, genomic stability, and more recently in senescence. Evidence has accumulated that Gadd45a deficiency results in escape of mouse embryo fibroblasts from senescence, whereas Gadd45b deficiency promotes premature senescence and skin aging. Moreover, recently Gadd45b deficiency was found to promote senescence and attenuate liver fibrosis, whereas Gadd45a was observed to exert a protective effect against hepatic fibrosis. These findings indicate that the Gadd45 stress response proteins play important roles in modulating cellular responses to senescence. Thus, exploring how Gadd45 proteins modulate cellular senescence has the potential to provide new and innovative tools to treat cancer as well as liver disease.

Interferon-gamma induces melanogenesis via post-translational regulation of tyrosinase.

Melanogenesis (melanin pigment production) in melanocytes is canonically stimulated by the alpha melanocyte stimulating hormone (αMSH), which activates the cyclic-AMP-mediated expression of the melanocyte inducing transcription factor (MITF) and its downstream melanogenic genes, including the principal rate-limiting melanogenic enzyme tyrosinase (TYR). Here, we report that interferon-gamma (IFNG; type II interferon), but not interferon-alpha (a type I interferon), induces a noncanonical melanogenic pathway in mouse and human melanocytic cells. Inhibition of IFNG pathway by the JAK1/2 inhibitor ruxolitinib or knocking out Stat1 gene abrogated the IFNG-induced melanogenesis. Interestingly, IFNG-induced melanogenesis was independent of MITF. IFNG markedly increased the TYR protein expression but did not affect the mRNA expression, suggesting a post-translational regulatory mechanism. In contrast, IFNG had no effect on the expression of other melanogenesis-related proteins, for example, tyrosinase-related protein 1 (TYRP1) and dopachrome tautomerase (DCT). Glycosidase digestion assays revealed that IFNG treatment increased the mature glycosylated form of TYR, but not its de novo synthesis. Moreover, cycloheximide chase assay showed that degradation of TYR was decreased in IFNG-treated cells. These results suggest that the IFNG-STAT1 pathway regulates melanogenesis via regulation of the post-translational processing and protein stability of TYR.

Lead in the marine environment: concentrations and effects on invertebrates.

Lead (Pb) is a non-essential metal naturally present in the environment and often complexed with other elements (e.g., copper, selenium, zinc). This metal has been used since ancient Egypt and its extraction has grown in the last centuries. It has been used until recently as a fuel additive and is currently used in the production of vehicle batteries, paint, and plumbing. Marine ecosystems are sinks of terrestrial contaminations; consequently, lead is detected in oceans and seas. Furthermore, lead is not biodegradable. It remains in soil, atmosphere, and water inducing multiple negative impacts on marine invertebrates (key species in trophic chain) disturbing ecological ecosystems. This review established our knowledge on lead accumulation and its effects on marine invertebrates (Annelida, Cnidaria, Crustacea, Echinodermata, and Mollusca). Lead may affect different stages of development from fertilization to larval development and can also lead to disturbance in reproduction and mortality. Furthermore, we discussed changes in the seawater chemistry due to Ocean Acidification, which can affect the solubility, speciation, and distribution of the lead, increasing potentially its toxicity to marine invertebrates.

Ultrasound-positive axillary lymph nodes in early breast cancer: can a patient subgroup avoid axillary lymph node dissection? A simple algorithm is suggested.

INTRODUCTION: National UK guidelines suggest that axillary lymph node dissection (ALND) is no longer mandatory for selected early node-positive breast cancer patients. Our study aimed to identify patients with early breast cancer and ultrasound (USS)-positive axillary metastasis who possess low burden of axillary disease and can avoid ALND. METHODS: We conducted a 5-year study of prospectively collected data of patients with clinically T1-2, N0 breast cancer and a positive USS-guided axillary biopsy. Primary outcome was involvement of 1-2 lymph nodes (low disease burden) or ≥3 lymph nodes (higher axillary disease) on final ALND histology. Tumour type, size, grade, multifocality, receptor status, number of abnormal imaged nodes and presence of lympho-vascular invasion (LVI) were recorded. Data were analysed using chi-squared and Student's t-test. RESULTS: One hundred and sixty-six patients underwent ALND for pT1-2 breast cancer. Seventy patients had no clinically palpable lymphadenopathy but a positive USS-guided biopsy. Of 70 patients, 32 women (46%) had low disease burden, whereas 38 women (54%) had higher axillary disease in final histology. LVI and >1 abnormal lymph node on USS were both significantly associated with higher disease burden (p = 0.050 and 0.009, respectively). CONCLUSION: Our study confirms the presence of an important patient cohort, who are clinically node-negative with a positive USS-guided biopsy and a low volume of axillary disease. No imaging modality currently has the accuracy required to identify patients with this low disease burden preoperatively but we propose a simple algorithm for axillary management in this subgroup.

Advanced breast conservation and partial breast reconstruction - a review of current available options for oncoplastic breast surgery.

Breast cancer is the most common cancer affecting one in three women with new cancer diagnosis in England. Breast-conserving surgery is the primary surgical option in a vast majority of these patients. Use of oncoplastic techniques in breast conservation surgery has significantly improved the aesthetic outcomes without compromising the oncological safety of cancer resections. Oncoplastic breast-conserving surgery (OPBCS) has transformed the specialty with a paradigm shift in ideology and the recognition that aesthetic and oncological resections are synonymous when planning surgical intervention for patients with breast cancer. The two main options for OPBCS are therapeutic mammoplasty and partial beast reconstruction using pedicle-based flaps. This review aims to highlight key concepts in OPBCS demonstrating an overview of these surgical techniques, their safety, outcomes and the emergence of extreme oncoplastic breast surgery.

Loss of ELF5-FBXW7 stabilizes IFNGR1 to promote the growth and metastasis of triple-negative breast cancer through interferon-γ signalling.

Triple-negative breast cancer (TNBC) is characterized by a high degree of immune infiltrate in the tumour microenvironment, which may influence the fate of TNBC cells. We reveal that loss of the tumour suppressive transcription factor Elf5 in TNBC cells activates intrinsic interferon-γ (IFN-γ) signalling, promoting tumour progression and metastasis. Mechanistically, we find that loss of the Elf5-regulated ubiquitin ligase FBXW7 ensures stabilization of its putative protein substrate IFN-γ receptor 1 (IFNGR1) at the protein level in TNBC. Elf5low tumours show enhanced IFN-γ signalling accompanied by an increase of immunosuppressive neutrophils within the tumour microenvironment and increased programmed death ligand 1 expression. Inactivation of either programmed death ligand 1 or IFNGR1 elicited a robust anti-tumour and/or anti-metastatic effect. A positive correlation between ELF5 and FBXW7 expression and a negative correlation between ELF5, FBXW7 and IFNGR1 expression in the tumours of patients with TNBC strongly suggest that this signalling axis could be exploited for patient stratification and immunotherapeutic treatment strategies for Elf5low patients with TNBC.

Suppression of Ca2+ signals by EGR4 controls Th1 differentiation and anti-cancer immunity in vivo.

While the zinc finger transcription factors EGR1, EGR2, and EGR3 are recognized as critical for T-cell function, the role of EGR4 remains unstudied. Here, we show that EGR4 is rapidly upregulated upon TCR engagement, serving as a critical "brake" on T-cell activation. Hence, TCR engagement of EGR4-/- T cells leads to enhanced Ca2+ responses, driving sustained NFAT activation and hyperproliferation. This causes profound increases in IFNγ production under resting and diverse polarizing conditions that could be reversed by pharmacological attenuation of Ca2+ entry. Finally, an in vivo melanoma lung colonization assay reveals enhanced anti-tumor immunity in EGR4-/- mice, attributable to Th1 bias, Treg loss, and increased CTL generation in the tumor microenvironment. Overall, these observations reveal for the first time that EGR4 is a key regulator of T-cell differentiation and function.

Melanoblast transcriptome analysis reveals pathways promoting melanoma metastasis.

Cutaneous malignant melanoma is an aggressive cancer of melanocytes with a strong propensity to metastasize. We posit that melanoma cells acquire metastatic capability by adopting an embryonic-like phenotype, and that a lineage approach would uncover metastatic melanoma biology. Using a genetically engineered mouse model to generate a rich melanoblast transcriptome dataset, we identify melanoblast-specific genes whose expression contribute to metastatic competence and derive a 43-gene signature that predicts patient survival. We identify a melanoblast gene, KDELR3, whose loss impairs experimental metastasis. In contrast, KDELR1 deficiency enhances metastasis, providing the first example of different disease etiologies within the KDELR-family of retrograde transporters. We show that KDELR3 regulates the metastasis suppressor, KAI1, and report an interaction with the E3 ubiquitin-protein ligase gp78, a regulator of KAI1 degradation. Our work demonstrates that the melanoblast transcriptome can be mined to uncover targetable pathways for melanoma therapy.

Macroenvironment-gene-microenvironment interactions in ultraviolet radiation-induced melanomagenesis.

Cutaneous malignant melanoma is one of the few major cancers that continue to exhibit a positive rate of increase in the developed world. A wealth of epidemiological data has undisputedly implicated ultraviolet radiation (UVR) from sunlight and artificial sources as the major risk factor for melanomagenesis. However, the molecular mechanisms of this cause-and-effect relationship remain murky and understudied. Recent efforts on multiple fronts have brought unprecedented expansion of our knowledge base on this subject and it is now clear that melanoma is caused by a complex interaction between genetic predisposition and environmental exposure, primarily to UVR. Here we provide an overview of the effects of the macroenvironment (UVR) on the skin microenvironment and melanocyte-specific intrinsic (mostly genetic) landscape, which conspire to produce one of the deadliest malignancies.

Tobacco smoking in crosslinked keratoconus patients.

PURPOSE: The aim of this study was to evaluate the possibly protective link of smoking in keratoconic patients treated with accelerated cross-linking. METHODS: A telephone survey was conducted among 80 KC patients treated by accelerated cross-linking (A-CXL). The questions focused on general history, possible atopy and smoking habits. Results were compared to those of the general population by indirect standardization by age and sex according to the French national INPES survey. RESULTS: Sixty-two patients with KC were analyzed. The mean age at diagnosis was 22 years (SD 5). The mean age at which A-CXL was performed was 23 years (SD 6). Daily smokers represented 19 %, occasional smokers 8 %, ex-smokers 21 % and non-smokers 52 %. The mean age at which the patients began smoking was 17 (SD 2) years. Ex-smokers quit at a mean age of 24 (SD 4) years. The observed rates and expected rates of daily smokers were 19 % and 39 % respectively at the time of the survey (P=0.01), 24 % and 35 % at the time of the A-CXL treatment (P=0.10) and 31 % and 35 % at the time of diagnosis (P=0.58). The decrease in the rate of observed daily smokers over time was significant (P=0.02). DISCUSSION: Our data does not appear to suggest a significant protective effect of smoking on the occurrence of KC. It shows a lesser proportion of smokers in KC patients after A-CXL, but this difference did not exist at the time of KC diagnosis.

Reconstruction of exenteration socket with Integra® dermal substitute and skin graft.

The authors report their experience with the use of Integra® dermal substitute, in combination with a thin skin graft, following an orbital exenteration. The clinical case described relates to a 42-year-old gentleman with an ulcerative retractile lesion of the right lower eyelid. Histopathological examination diagnosed a moderately differentiated epidermoid carcinoma infiltrating the orbit. Total exenteration was necessary as well as secondary radiation therapy and chemotherapy. Rehabilitation of the exenterated socket was performed by inserting an Integra® patch, followed by an additional thin skin graft one month later. The authors review the various available techniques for exenterations, their indications and the various possible secondary rehabilitations. Despite being less utilized, the dermal substitute technique, which is relatively new, seems to offer quicker and easier rehabilitation compared to traditional techniques. A comparative study would be necessary to define superiority among the different techniques of exenteration, with respect to the speed of rehabilitation and resistance to radiation therapy.

Supracapsular phacoemulsification: Description of the "Garde à vous" technique and comparative clinical results.

Phacoemulsification techniques can be divided into 2 categories: endocapsular and supracapsular techniques. Supracapsular techniques involve phacoemulsification of the nucleus outside and above the capsular plane. The "Garde-à-vous" technique described in this manuscript is a modified and improved version of the supracapsular procedure with up-to-date technology in micro-coaxial surgery. It maintains the known advantages of supracapsular techniques such as faster surgical times and lower rates of capsular tears and brings a standardized technique with well-defined surgical steps in order to achieve tilting of the nucleus in a vertical or oblique position in almost 100% of cases by performing a double-wave hydro-dissection. The authors also give the results of a non-randomized prospective study, comparing the "Garde-à-vous" technique and the standard "cracking" technique in 2856 cases. The results show that for the "Garde-à-vous group", the patients were significantly younger (P<0.001), the power of ultrasound used was greater (P<0.001) for lower UST (ultrasound time or average phacoemulsification time APT) and EPT (effective phacoemulsication time) (P<0.001), the duration of the procedure was shorter (P<0.001), patient discomfort was less (P<0.001), and the power of the implants used was lower (P<0.01). With regard to the gender of the patients, the percentage of topical anesthesia and the rate of intraoperative complications (posterior capsular rupture), there was no statistically significant difference.