Preventing crossinfection during reflectance confocal microscopy, using a transparent film dressing.

Contamination and crossinfection are always a significant concern when using reflectance confocal microscopy in the clinic because the glass window and metal ring at the front of the probe must contact the skin and mucosal surfaces, and sterilization of the imaging probes is usually impossible. We describe use of a transparent, single-use film dressing to solve this problem.

Haploidentical CD7 CAR T-cells induced remission in a patient with TP53 mutated relapsed and refractory early T-cell precursor lymphoblastic leukemia/lymphoma.

Patients with relapsed/refractory early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) respond poorly to traditional therapy and have dismal prognosis. CD7 is a promising therapeutic targets for chimeric antigen receptor modified T cell therapy (CART) due to its widely expression in almost all T-cell malignancies. Here we present the anti-CD7 CART therapy in a 11-year-old male with TP53 mutated relapsed/refractory ETP-ALL/LBL. The patient suffered second relapse after haploidentical hematopoietic stem cell transplantation, showing resistance to 4 lines salvage therapies including venetoclax. Nanobody derived CD7-CART cells were manufactured by co-transducing CAR-T cells with a CD7 protein expression blocker. 70.5% of blasts (CD7 expression: 92.6%) and extensive extramedullary disease (mediastinal mass, enlarged lymph nodes and spleen) were observed prior to CD7-CART-cell therapy. A total of 5 × 106/kg donor-derived CD7-CART-cells were infused. Hematological and extramedullary remission were both achieved, with persistence of CD7-CART-cells be detected until the last followup at 96th days after the infusion. Reversible adverse effects including grade 3 cytokine release syndrome and macrophage activation syndrome were observed. This case demonstrated that CD7-CART was a potent and safe salvage therapy in relapsed/refractory ETP-ALL/LBL patient with high tumor burden.Trial registration: ClinicalTrials. gov, NCT04785833 , Registered on March 8, 2021, prospectively registered.

Energy-saving electrolytic γ-MnO2 generation: non-noble metal electrocatalyst gas diffusion electrode as cathode in acid solution.

γ-MnO2, which is commercially used as an electrode material in batteries, is produced using large amounts of energy and leads to the production of high pollution as a secondary product. Ideally, this material should be fabricated by energy efficient, non-polluting methods at a reasonable cost. This study reports the green fabrication of γ-MnO2 into a gas diffusion electrode with Pt-free catalysts in acid solution. Cobalt oxide nanoparticles were deposited on few-layer graphene sheets produced via a simple sintering and ultrasonic mixing method, leading to the fabrication of cobalt oxide/few-layer graphene. Co3O4 nanoparticles are irregularly shaped and uniformly distributed on the surface of the few-layer graphene sheets. Characterization was conducted by X-ray diffraction, X-ray photoelectron spectroscopy, and field emission scanning electron microscopy. Electrochemical characterization revealed the performance of cobalt oxide/few-layer graphene gas diffusion electrode in an electrolyte of 120 g L-1 manganese sulfate + 30 g L-1 sulfuric acid at 100 A m-2 at 80 °C. The cobalt oxide/few-layer graphene gas diffusion electrode exhibited a lower cell voltage of 0.9 V and higher electric energy savings of approximately 50% compared with traditional cathodes (copper and carbon).

Biosynthesis of nervonic acid and perspectives for its production by microalgae and other microorganisms.

Nervonic acid (NA) is a major very long-chain monounsaturated fatty acid found in the white matter of mammalian brains, which plays a critical role in the treatment of psychotic disorders and neurological development. In the nature, NA has been synthesized by a handful plants, fungi, and microalgae. Although the metabolism of fatty acid has been studied for decades, the biosynthesis of NA has yet to be illustrated. Generally, the biosynthesis of NA is considered starting from oleic acid through fatty acid elongation, in which malonyl-CoA and long-chain acyl-CoA are firstly condensed by a rate-limiting enzyme 3-ketoacyl-CoA synthase (KCS). Heterologous expression of kcs gene from high NA producing species in plants and yeast has led to synthesis of NA. Nevertheless, it has also been reported that desaturases in a few plants can catalyze very long-chain saturated fatty acid into NA. This review highlights recent advances in the biosynthesis, the sources, and the biotechnological aspects of NA.

HMGB1 Promotes Mitochondrial Dysfunction-Triggered Striatal Neurodegeneration via Autophagy and Apoptosis Activation.

Impairments in mitochondrial energy metabolism are thought to be involved in many neurodegenerative diseases. The mitochondrial inhibitor 3-nitropropionic acid (3-NP) induces striatal pathology mimicking neurodegeneration in vivo. Previous studies showed that 3-NP also triggered autophagy activation and apoptosis. In this study, we focused on the high-mobility group box 1 (HMGB1) protein, which is important in oxidative stress signaling as well as in autophagy and apoptosis, to explore whether the mechanisms of autophagy and apoptosis in neurodegenerative diseases are associated with metabolic impairment. To elucidate the role of HMGB1 in striatal degeneration, we investigated the impact of HMGB1 on autophagy activation and cell death induced by 3-NP. We intoxicated rat striata with 3-NP by stereotaxic injection and analyzed changes in expression HMGB1, proapoptotic proteins caspase-3 and phospho-c-Jun amino-terminal kinases (p-JNK). 3-NP-induced elevations in p-JNK, cleaved caspase-3, and autophagic marker LC3-II as well as reduction in SQSTM1 (p62), were significantly reduced by the HMGB1 inhibitor glycyrrhizin. Glycyrrhizin also significantly inhibited 3-NP-induced striatal damage. Neuronal death was replicated by exposing primary striatal neurons in culture to 3-NP. It was clear that HMGB1 was important for basal autophagy which was shown by rescue of cells through HMGB1 targeting shRNA approach.3-NP also induced the expression of HMGB1, p-JNK, and LC3-II in striatal neurons, and p-JNK expression was significantly reduced by shRNA knockdown of HMGB1, an effect that was reversed by exogenously increased expression of HMGB1. These results suggest that HMGB1 plays important roles in signaling for both autophagy and apoptosis in neurodegeneration induced by mitochondrial dysfunction.

Comparative transcriptomic analysis of the heat stress response in the filamentous fungus Metarhizium anisopliae using RNA-Seq.

The entomopathogenic fungus Metarhizium anisopliae is widely used for biological control of a variety of insect pests. The effectiveness of the microbial pest control agent, however, is limited by poor thermotolerance. The molecular mechanism underlying the response to heat stress in the conidia of entomopathogenic fungi remains unclear. Here, we conducted high-throughput RNA-Seq to analyze the differential gene expression between control and heat treated conidia of M. anisopliae at the transcriptome level. RNA-Seq analysis generated 6,284,262 and 5,826,934 clean reads in the control and heat treated groups, respectively. A total of 2,722 up-regulated and 788 down-regulated genes, with a cutoff of twofold change, were identified by expression analysis. Among these differentially expressed genes, many were related to metabolic processes, biological regulation, cellular processes and response to stimuli. The majority of genes involved in endocytic pathways, proteosome pathways and regulation of autophagy were up-regulated, while most genes involved in the ribosome pathway were down-regulated. These results suggest that these differentially expressed genes may be involved in the heat stress response in conidia. As expected, significant changes in expression levels of genes encoding heat shock proteins and proteins involved in trehalose accumulation were observed in conditions of heat stress. These results expand our understanding of the molecular mechanisms of the heat stress response of conidia and provide a foundation for future investigations.

[Clinical characteristics and survival analysis of 22 cases of pure epithelial breast metaplastic carcinoma].

OBJECTIVE: Pure epithelial breast metaplastic carcinoma is a rare and highly malignant tumor. In this study, our purpose was to analyze the clinical features, treatment method and prognostic factors, so to explore the approach for early diagnosis and appropriate treatment of this cancer. METHODS: Clinical data of 22 patients with histopathologically confirmed pure epithelial breast metaplastic carcinoma and treated at Tianjin Cancer Hospital from 1974 to 2008, were reviewed retrospectively. Survival rate was calculated by life tables. Kaplan-Meier unvariate analysis and Log-rank test were used to compare the survival rates. Multivariate factors for survival were analyzed by Cox proportional hazards regression model. RESULTS: The median age of the 22 cases of pure epithelial breast metaplastic carcinoma was 52.5 years. Among them 20 cases went to see a doctor for painless mass, and two cases shown as skin inflammation. Clarifying a diagnosis was difficult before operation so that its diagnosis mainly depended on postoperative histopathologic examination. Twelve cases had axillary lymph node metastasis, 7 cases distant metastasis, and the lung was the most common metastatic organ. The 5-year survival rate was 55.6%, with a median follow-up of 46 months. It was found by Kaplan-Meier unvariate analysis that the age (P = 0.044), number of positive axillary lymph nodes (P = 0.011) and therapeutic schedule (P = 0,003) significantly influenced the outcome of the patients, but tumor size (P = 0.194) was not. Cox multivariate analysis results showed that number of positive axillary lymph nodes was independent prognostic factor for pure epithelial breast metaplastic carcinoma (P = 0.038). CONCLUSIONS: Pure epithelial breast metaplastic carcinoma is seldom seen. It is easy to cause distant metastasis and has a poor prognosis. ER, PR and HER-2 expressions in most samples are negative. The more axillary lymph nodes have metastasis, the poorer is the prognosis. A reasonable and comprehensive treatment can improve the prognosis obviously.

MicroRNA and histopathological characterization of pure mucinous breast carcinoma.

OBJECTIVE: Pure mucinous breast carcinoma (PMBC) is an uncommon histological type of breast cancer characterized by a large amount of mucin production. MicroRNA (miRNA) is a large class of small noncoding RNA of about 22 nt involved in the regulation of various biological processes. This study aims to identify the miRNA expression profile in PMBC. METHODS: MiRNA expression profiles in 11 PMBCs were analyzed by miRNA-microarray and real-time polymerase chain reaction (PCR). Thirty-one PMBCs and 27 invasive ductal carcinoma of no special types (IDC-NSTs) were assessed by immunohistochemistry using antibodies against ER, PR-progesterone receptor, HER2, Ki-67, Bcl-2, p53, PCNA, and CK5 and 6. RESULTS: We analyzed the miRNA expression in 11 PMBCs and corresponding normal tissues using miRNA-microarray and real-time PCR, and found that miR-143 and miR-224-5p were significantly downregulated in mucinous carcinoma tissue. Compared with IDC-NSTs, PMBC showed a significantly higher ER positive rate, lower HER-2 positive rate, and lower cell proliferation rates. CONCLUSIONS: To our knowledge, this is the first study to demonstrate the miRNA expression profile of PMBC, and our findings may lead to further understanding of this type of breast cancer.

Snail as a key regulator of PRL-3 gene in colorectal cancer.

The regulators of a key metastasis gene PRL-3 in colorectal cancer (CRC) are still largely unknown. We found three potential binding sites of Snail, a key transcriptional factor involved in the epithelial-mesenchymal transition (EMT), in the region of PRL-3 promoter (located at -642 to -383). Moreover, our results showed that one of the Snail binding sites (located at -624 to -619) was the key element to maintain promoter activity of human PRL-3 gene. The transcriptional activity of PRL-3 promoter was abolished after the Snail binding site (located at -624 to -619) was mutated. Both promoter activity and protein expression of PRL-3 in CRC cell lines could be regulated by Snail. In clinical samples of CRC and metastatic lymph node of CRC, expression of PRL-3 protein was correlated with expression of Snail protein. Functional studies using gene over-expression and knockdown methods indicated that Snail promoted proliferation, cell adhesion and migration of human CRC cells. In SW480 cells with PRL-3 stable knockdown, cell proliferation increased after Snail was up-regulated. Our data first reveal transcriptional factor Snail as a key regulator of PRL-3 in CRC. The link between Snail and PRL-3 suggests a new potential mechanism of Snail contributing to progression and metastasis of CRC.

[A photographic scale for evaluating facial pores and analysis of factors associated with pore widening in Chengdu].

OBJECTIVE: To develop a photographic scale for grading widening of pores, and to identify the factors associated with pore widening. METHODS: People with widened pores were recruited, with photographs taken on their nasal tips, nasal alas and cheeks. A questionnaire survey was undertaken by dermatologists to assess the severity of pore widening. A Cumulative Logit Model was established to identify factors that were associated with pore widening. RESULTS: A total of 115 people participated in the study and 562 photographs were taken. The photographic scale was highly consistent with the clinical judgment. Another 1011 residents aged from 18 to 70 years old in Chengdu were surveyed. The logit model revealed that facial pore widening were associated with gender, age, oily skin, sun protection and anti-aging cosmetic. CONCLUSION: The photographic scale is reliable and easy to use. Gender, age and oily skin are risk factors, and sun protection and anti-aging cosmetic are protective factors with related to pore widening.

Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer.

We studied the expression and regulatory effects of ESC self-renewal molecule Nanog in colorectal cancer (CRC). Immunohistochemical analysis of 175 colorectal tumor samples showed that overexpression of Nanog was strongly correlated with poor prognosis, lymph node metastasis and Dukes classification for CRC. Univariate and multivariate survival analyses further indicated that Nanog expression was a potential prognostic factor for CRC. Gain-of-function analysis revealed that lentivirus-mediated Nanog overexpression promoted proliferation, motility and migration of human CRC cells. Interestingly, we found that Nanog played as both an inducer and a receipt of epithelial-mesenchymal transition (EMT) related signals. Nanog induced expression of Slug and Snail, two major regulator of EMT. Meanwhile, Nanog could also be regulated by Snail and initiated by TGF-ß1. Our data demonstrate self-renewal gene Nanog has a prognostic role in CRC, which functions in progression of CRC by promoting proliferation, invasion, and motility of human CRC cells, and participates EMT process during CRC progression.