Phospholipase C Delta 3 inhibits apoptosis and promotes proliferation, migration, and invasion of thyroid cancer cells via Hippo pathway.

In recent decades, the incidence of thyroid cancer (TC) has rapidly increased, leading us to explore the complex underlying mechanisms. We identified the gene Phospholipase C Delta 3 (PLCD3) as a potential oncogene in TC by conducting the whole transcriptome sequencing. Our study is to understand the oncogenic role of PLCD3 in TC. We verified the overexpression of PLCD3 in TC from The Cancer Genome Atlas, Gene Expression Omnibus databases, and a locally validated cohort. Clinical correlation analysis showed that PLCD3 expression was related to histological type, T stage, lymph node metastasis (LNM), and disease stage. The high expression of PLCD3 could be a distinguishing factor for TC and its LNM. The biological function was examined using small interfering RNA-transfected TC cell lines. Silenced PLCD3 could inhibit colony formation, migration, and invasion ability and promote apoptosis of TC cell lines. PLCD3 silencing reversed the epithelial-mesenchymal transition but induced the apoptotic progress. Further exploration revealed that PLCD3 might be associated with critical genes of the Hippo pathway. The expressions of RHOA, YAP1/TAZ, and their downstream targets were decreased significantly when PLCD3 was down-regulated. YAP1 overexpression rescued the tumor-suppressive effect caused by PLCD3 silencing. This study demonstrates that PLCD3 is an oncogene that supports tumorigenesis and progression in TC, and PLCD3 may be a potential target gene for TC treatment.

Intestinal Microbiota Is Altered in Patients with Gastric Cancer from Shanxi Province, China.

BACKGROUND: Many diseases have been associated with intestinal microbial dysbiosis. Host-microbial interactions regulate immune function, which influences the development of gastric cancer. AIMS: The aims were to investigate the characteristics of intestinal microbiota composition in gastric cancer patients and correlations between the intestinal microbiota and cellular immunity. METHODS: Fecal samples were collected from 116 gastric cancer patients and 88 healthy controls from Shanxi Province, China. The intestinal microbiota was investigated by 16S rRNA gene sequencing. Peripheral blood samples were also collected from the 66 gastric cancer patients and 46 healthy controls. The populations of peripheral T lymphocyte subpopulations and NK cells were analyzed by flow cytometry. RESULTS: The intestinal microbiota in gastric cancer patients was characterized by increased species richness, decreased butyrate-producing bacteria, and the enrichment of other symbiotic bacteria, especially Lactobacillus, Escherichia, and Klebsiella. Lactobacillus and Lachnospira were key species in the network of gastric cancer-associated bacterial genera. The combination of the genera Lachnospira, Lactobacillus, Streptococcus, Veillonella, and Tyzzerella_3 showed good performance in distinguishing gastric cancer patients from healthy controls. There was no significant difference in enterotype distribution between healthy controls and gastric cancer patients. The percentage of CD3+ T cells was positively correlated with the abundance of Lactobacillus and Streptococcus, and CD3+ T cells, CD4+ T cells, and NK cells were associated with Lachnospiraceae taxa. CONCLUSIONS: Our study revealed a dysbiotic intestinal microbiota in gastric cancer patients. The abundance of some intestinal bacterial genera was correlated with the population of peripheral immune cells.

Cross-domain policy adaptation with dynamics alignment.

The implementation of robotic reinforcement learning is hampered by problems such as an unspecified reward function and high training costs. Many previous works have used cross-domain policy transfer to obtain the policy of the problem domain. However, these researches require paired and aligned dynamics trajectories or other interactions with the environment. We propose a cross-domain dynamics alignment framework for the problem domain policy acquisition that can transfer the policy trained in the source domain to the problem domain. Our framework aims to learn dynamics alignment across two domains that differ in agents' physical parameters (armature, rotation range, or torso mass) or agents' morphologies (limbs). Most importantly, we learn dynamics alignment between two domains using unpaired and unaligned dynamics trajectories. For these two scenarios, we propose a cross-physics-domain policy adaptation algorithm (CPD) and a cross-morphology-domain policy adaptation algorithm (CMD) based on our cross-domain dynamics alignment framework. In order to improve the performance of policy in the source domain so that a better policy can be transferred to the problem domain, we propose the Boltzmann TD3 (BTD3) algorithm. We conduct diverse experiments on agent continuous control domains to demonstrate the performance of our approaches. Experimental results show that our approaches can obtain better policies and higher rewards for the agents in the problem domains even when the dataset of the problem domain is small.

Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway.

BACKGROUND: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity. METHODS: A heterograft mouse model using triple negative breast cancer (TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis. RESULTS: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro. In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal model of breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth. CONCLUSIONS: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy.

Efficient Electrooxidation of 5-Hydroxymethylfurfural Using Co-Doped Ni3 S2 Catalyst: Promising for H2 Production under Industrial-Level Current Density.

Replacing oxygen evolution reaction (OER) by electrooxidations of organic compounds has been considered as a promising approach to enhance the energy conversion efficiency of the electrolytic water splitting proces. Developing efficient electrocatalysts with low potentials and high current densities is crucial for the large-scale productions of H2 and other value-added chemicals. Herein, non-noble metal electrocatalysts Co-doped Ni3 S2 self-supported on a Ni foam (NF) substrate are prepared and used as catalysts for 5-hydroxymethylfurfural (HMF) oxidation reaction (HMFOR) under alkaline aqueous conditions. For HMFOR, the Co0.4 NiS@NF electode achieves an extremely low onset potential of 0.9 V versus reversible hydrogen electrode (RHE) and records a large current density of 497 mA cm-2 at 1.45 V versus RHE for HMFOR. During the HMFOR-assisted H2 production, the yield rates of 2,5-furandicarboxylic acid (FDCA) and H2 in a 10 mL electrolyte containing 10 × 10-3 M HMF are 330.4 µmol cm-2 h-1 and 1000 µmol cm-2 h-1 , respectively. The Co0.4 NiS@NF electrocatalyst displays a good cycling durability toward HMFOR and can be used for the electrooxidation of other biomass-derived chemicals. The findings present a facile route based on heteroatom doping to fabricate high-performance catalyses that can facilitate the industrial-level H2 production by coupling the conventional HER cathodic processes with HMFOR.

Studies on stratum corneum metabolism: function, molecular mechanism and influencing factors.

BACKGROUND: Stratum corneum is located in the outermost layer of the skin and is the most important part of the skin barrier. Stratum corneum mainly contains keratinocytes, lipids, and desmosomes. Their normal metabolic process is closely related to the function of skin barrier. AIMS: This paper reviews the structure and function of stratum corneum, influencing factors, skin diseases, and common solutions. METHODS: An extensive literature search was conducted on the structure and function of stratum corneum, influencing factors, skin diseases, and common solutions. RESULTS: This paper reviews the structure and function of stratum corneum and the influence of various factors on stratum corneum metabolism. At the same time, the existing skin problems, skin diseases, and common solutions are summarized. CONCLUSIONS: This information will help to understand the function, molecular mechanism, and influencing factors of stratum corneum metabolism, and provide new ideas for stratum corneum health management and cosmetic research and development.

Application of epigenetics in dermatological research and skin management.

BACKGROUND: Epigenetics has recently evolved from a collection of diverse phenomena to a defined and far-reaching field of study. Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in some skin diseases or cancer. AIMS: The purpose of this article was to review the development of epigenetic in recent decades and their applications in dermatological research. METHODS: An extensive literature search was conducted on epigenetic modifications since the first research on epigenetic. RESULTS: This article summarizes the concept and development of epigenetics, as well as the process and principle of epigenetic modifications such as DNA methylation, histone modification, and non-coding RNA. Their application in some skin diseases and cosmetic research and development is also summarized. CONCLUSIONS: This information will help to understand the mechanisms of epigenetics and some non-coding RNA, the discovery of the related drugs, and provide new insights for skin health management and cosmetic research and development.

SPTBN2 Promotes the Progression of Thyroid Cancer by Accelerating G1/S Transition and Inhibiting Apoptosis.

Background: Thyroid carcinoma (TC) is an increasingly common malignancy of endocrine organs, and its most frequently encountered histotype is papillary thyroid cancer (PTC). Identifying new potential gene alterations is important for completely elucidating the mechanism of PTC initiation and progression. Thus, we performed whole transcriptome sequence analysis (RNA-seq) on 79 PTC tissue samples and paired adjacent nontumor tissue samples to study the molecular mechanism of TC tumorigenesis and progression further. The results of RNA-seq analysis showed that spectrin beta, nonerythrocytic 2 (SPTBN2), was markedly overexpressed in PTC tissues relative to that in the paired nontumor tissues. Additionally, the analysis results for 502 PTC samples and 58 nontumor thyroid samples from The Cancer Genome Atlas dataset were consistent with our RNA-seq results. However, the molecular mechanisms and function of SPTBN2 in TC progression remain unknown. Methods: We examined SPTBN2 gene expression in 48 papillary thyroid tumor tissues and paired adjacent normal thyroid tissues by using qRT-PCR. SPTBN2 expression in the TC cell lines was silenced by small interfering RNA. Then, the transfected TC cells were used to investigate the in vitro function of SPTBN2. Result: The expression of SPTBN2 was significantly upregulated in our RNA-seq cohort, our local validated cohort, and TCGA RNA-seq cohort. The results of the in vitro experiment revealed that in TC cell lines, SPTBN2 downregulation considerably suppressed tumor cell proliferation, the cell cycle, migration, colony formation, and invasion and induced cell apoptosis. Furthermore, the protein levels of CCNE2, CDK2, CDK4, and Bcl-2 were downregulated, and those of P21, Bax, cleaved caspase-8, and cleaved caspase-3 had increased in transfected TC cells relative to in control TC cells. Conclusion: The downregulation of SPTBN2 caused apoptosis and retarded G1/S cell cycle transition in TC cells. Thus, SPTBN2 may be a good candidate gene for TC diagnosis and therapy.

Downstream Neighbor of Son Overexpression is Associated With Breast Cancer Progression and a Poor Prognosis.

PURPOSE: The incidence rate of breast cancer (BC) has increased annually. Downstream neighbor of son (DONSON) critically affects cell cycle progression and maintains stable genomic properties; however, its relevant effects on BC growth and progression require in-depth investigation. METHODS: DONSON upregulation was validated in public databases. DONSON expression in matched BC and adjacent tissues and cell lines (MDA-MB-231, BT-549, and HS-578T) was determined using quantitative reverse transcription polymerase chain reaction. In vitro apoptosis, invasion, migration, and proliferation tests were performed to ascertain the functions of DONSON in BC cell lines. Then, using western blot analysis, the levels of DONSON downstream proteins were determined. RESULTS: Compared to the control, DONSON was expressed at higher levels in BC tissues and cell lines. DONSON knockdown facilitated apoptosis and limited proliferation, migration, invasion, and S/G2 transition of BC cells in vitro. Furthermore, DONSON overexpression promoted BC cell proliferation and inhibited apoptosis in vitro. Moreover, DONSON knockdown reduced cyclin A1 and cyclin-dependent kinase 2 levels. Moreover, DONSON knockdown limited the progression of epithelial-mesenchymal transition. CONCLUSION: DONSON critically affects BC growth and serves as a possible target and marker for the efficacy of subsequent therapies.

The ETNK2 gene promotes progression of papillary thyroid carcinoma through the HIPPO pathway.

Thyroid cancer is a disease with an extremely high incidence rate and is divided into papillary, follicular, medullary, and undifferentiated thyroid cancers. Among them, papillary carcinoma is the most common subtype. We assessed expression of ETNK2 in public databases and found that ETNK2 is upregulated in PTC. Cohort and RNA sequencing data were used to verify this discovery. To further determine the relationship between ETNK2 and papillary thyroid carcinoma, we performed an in vitro experiment. In a PTC cell line, silencing ETNK2 inhibited cell proliferation, weakened cell migration and invasion ability, promoted apoptosis, and blocked the cell cycle. In addition, western blotting suggested that ETNK2 is related to the HIPPO pathway and may activate the EMT pathway through the HIPPO pathway to promote the development of thyroid cancer. These results revealed that ETNK2 is related to the occurrence and development of papillary thyroid carcinoma, suggesting that ETNK2 may be an oncogene associated with PTC.

Vanadium-Doping and Interface Engineering for Synergistically Enhanced Electrochemical Overall Water Splitting and Urea Electrolysis.

Fabricating effective non-precious metal-based catalysts for hydrogen production via electrochemical water splitting is of considerable importance but remains challenging. Transition metal nitrides possessing metallic character and corrosion resistance have been considered as potential replacements for precious metals. However, their activities for water electrolysis are impeded by the strong hydrogen adsorption and low water adsorption energies. Herein, V-doped bimetallic nitrides, V-FeNi3N/Ni3N heterostructure, are synthesized via a hydrothermal-nitridation protocol and used as electrocatalysts for water splitting and urea electrolysis. The V-FeNi3N/Ni3N electrode exhibits superior HER and OER activities, and the overpotentials are 62 and 230 mV to acquire a current density of 10 mA cm-2, respectively. Moreover, as a bifunctional electrocatalyst for overall water splitting, a two-electrode device needs a voltage of 1.54 V to reach a current density of 10 mA cm-2. The continuous electrolysis can be run for more than 120 h, surpassing most previously reported electrocatalysts. The excellent performance for water electrolysis is dominantly due to V-doping and interface engineering, which could enhance water adsorption and regulate the adsorption/desorption of intermediates species, thereby accelerating HER and OER kinetic processes. Besides, a urea-assisted two-electrode electrolyzer for electrolytic hydrogen production requires a cell voltage of 1.46 V at 10 mA cm-2, which is 80 mV lower than that of traditional water electrolysis.

Exploration of the Prognostic and Immunotherapeutic Value of B and T Lymphocyte Attenuator in Skin Cutaneous Melanoma.

B and T lymphocyte attenuator (BTLA) is a newly identified immune checkpoint molecular belonging to the CD28 immunoglobulin superfamily. However, the expression and clinical value of BTLA in skin cutaneous melanoma (SKCM) has not been widely characterized. We found that BTLA levels were upregulated in metastatic melanoma compared to normal skin tissues and primary melanoma. Higher BTLA was also correlated with improved prognosis in SKCM based on several datasets. The multivariate Cox regression model revealed that BTLA was an independent survival indicator in metastatic melanoma. Tumor microenvironment analysis indicated BTLA was positively associated with the infiltrating levels of different immune cells and the activity of the anti-cancer immunity cycle. Importantly, BTLA accurately predicted the outcome of melanoma patients treated with MAGE-A3 blocker or first-line anti-PD-1. The present findings disclose that BTLA is a reliable biomarker for prognosis and immunotherapeutic response and might contribute to developing novel SKCM immunological treatment strategies.

Self-supported Co-doped FeNi carbonate hydroxide nanosheet array as a highly efficient electrocatalyst towards the oxygen evolution reaction in an alkaline solution.

The evolution of molecular hydrogen from electrochemical water splitting has currently emerged as one of the promising strategies to address the ever-increasing energy crisis and environmental pollution. The development of low-cost, highly efficient and long-term durable electrocatalysts is still challenging for practical large-scale water splitting applications. Herein, a highly crystallized Co-doped FeNi carbonate hydroxide nanosheet array was strongly grown on a conductive nickel foam (Co-FeNi CH/NF) and was used as an oxygen evolution reaction (OER) electrocatalyst. The ternary Co-FeNi CH/NF electrode exhibited an improved OER activity and good durability for at least 20 hours. The electrode delivered current densities of 10 and 500 mA cm-2 at extremely low overpotentials of 202 and 254 mV along with a small Tafel slope of 37.5 mV dec-1 in a 1.0 M KOH electrolyte solution. The incorporation of an equivalent amount of cobalt into the trigonal FeNi CH crystal lattice significantly increased the electrochemical active surface area and reduced the electron transport resistance by effectively regulating the electronic structure of the resultant electrocatalyst. These interesting observations highlight the importance of the subtle combinations of the active earth-abundant metals with electronic structure modulations.