Prognostic prediction of oxidative stress related hematological biomarkers in locally advanced cervical cancer patients undergoing chemoradiotherapy.

OBJECTIVE: This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. METHODS: A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. RESULTS: A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (p = 0.001) and PFS (p < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. CONCLUSION: This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.

Effects of 6-methoxybenzoxazolinone (6-MBOA) on animals: state of knowledge and open questions.

6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-ß-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry.

TAZ reverses the inhibitory effects of LPS on the osteogenic differentiation of human periodontal ligament stem cells through the NF-κB signaling pathway.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are important candidate seed cells for periodontal tissue engineering, but the presence of lipopolysaccharide(LPS) in periodontal tissues inhibits the self-renewal and osteogenic differentiation of hPDLSCs. Our previous studies demonstrated that TAZ is a positive regulator of osteogenic differentiation of hPDLSCs, but whether TAZ can protect hPDLSCs from LPS is still unknown. The present study aimed to explore the regulatory effect of TAZ on the osteogenic differentiation of hPDLSCs in an LPS-induced inflammatory model, and to preliminarily reveal the molecular mechanisms related to the NF-κB signaling pathway. METHODS: LPS was added to the culture medium of hPDLSCs. The influence of LPS on hPDLSC proliferation was analyzed by CCK-8 assays. The effects of LPS on hPDLSC osteogenic differentiation were detected by Alizarin Red staining, ALP staining, Western Blot and qRT-PCR analysis of osteogenesis-related genes. The effects of LPS on the osteogenic differentiation of hPDLSCs with TAZ overexpressed or knocked down via lentivirus were analyzed. NF-κB signaling in hPDLSCs was analyzed by Western Blot and immunofluorescence. RESULTS: LPS inhibited the osteogenic differentiation of hPDLSCs, inhibited TAZ expression, and activated the NF-κB signaling pathway. Overexpressing TAZ in hPDLSCs partly reversed the negative effects of LPS on osteogenic differentiation and inhibited the activation of the NF-κB pathway by LPS. TAZ knockdown enhanced the inhibitory effects of LPS on osteogenesis. CONCLUSION: Overexpressing TAZ could partly reverse the inhibitory effects of LPS on the osteogenic differentiation of hPDLSCs, possibly through inhibiting the NF-κB signaling pathway. TAZ is a potential target for improving hPDLSC-based periodontal tissue regeneration in inflammatory environments.

HDAC1 suppresses radiotherapy sensitivity in cervical cancer via regulating HIF-1α/VEGF signaling pathway.

Cervical cancer (CC) is the fourth most common cancer amongst females worldwide. Histone deacetylase (HDAC) 1 plays a vital role in several tumors. Nevertheless, its potential and mechanism in radiotherapy sensitivity underlying CC remains obscure. Hence, the objective of this research was to probe the potential of HDAC1 in CC radiotherapy sensitivity and its mechanism of action. The expression HDACs and survival analysis of HDAC1 were investigated based on the GEPIA database. Immunohistochemical staining was implemented to detect HDAC1 and Ki-67 expression in tumor tissues. RT-qPCR and Western blot were conducted to assess HDAC1, HIF-1α, VEGFA, along with VEGFR expressions in CC cells and tumor tissues. Cell viability, apoptosis, invasion, migration, along with cell cycle were analyzed by functional assays. Tumor-bearing nude mice model was established, and the tumor weight and volume were determined. HDAC1 was high-expressed in the tumor tissue and CC cells. In vitro, overexpression of HDAC1 suppressed radiotherapy sensitivity in C33A cells, while knockdown of HDAC1 promoted radiotherapy sensitivity in SiHa cells. In vivo, we found that HDAC1 silence hindered tumor growth and cell proliferation and promoted tumor cell apoptosis in nude mice after radiotherapy. In addition, we found that HDAC1 impacted radiotherapy sensitivity by modulating the HIF-1α/VEGF signaling pathway. In conclusion, HDAC1 suppressed the radiotherapy sensitivity of CC via regulating HIF-1α/VEGF signaling pathway, suggesting that HDAC1 may act as a crucial participant in regulating CC radiosensitivity, which may provide a novel method for treating CC.

Calcium-sensing receptor protects intestinal integrity and alleviates the inflammatory response via the Rac1/PLCγ1 signaling pathway.

This study aimed to test the hypothesis that the calcium-sensing receptor (CaSR) can protect intestinal epithelial barrier integrity and decrease inflammatory response mediated by the Ras-related C3 botulinum toxin substrate 1 (Rac1)/phospholipase Cγ1 (PLC-γ1) signaling pathway. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of CaSR antagonist (NPS 2143), CaSR overexpression, and Rac1 silencing, PLCγ1 silencing or spermine. Results showed that spermine increased transepithelial electrical resistance (TER), tight junction protein levels, the protein concentration of Rac1/PLC-γ1 signaling pathway, and decreased paracellular permeability in the presence of TNF-α. NPS2143 inhibited spermine-induced change in above-mentioned parameters. CaSR overexpression increased TER, the levels of tight junction proteins and the protein concentration of CaSR, phosphorylated PLCγ1, Rac1, and IP3, and decreased paracellular permeability and contents of interleukin-8 (IL-8) and TNF-α after TNF-α challenge. Rac1 and PLCγ1 silencing inhibited CaSR-induced increase in barrier function and the protein concentration of phosphorylated PLCγ1, Rac1, and IP3, and decrease in contents of IL-8 and TNF-α after TNF-α challenge. These results suggest that CaSR activation protects intestinal integrity and alleviates the inflammatory response by activating Rac1 and PLCγ1 signaling after TNF-α challenge, and spermine can maintain barrier function via CaSR/Rac1/PLC-γ1 pathway.

Tryptophan alleviates lipopolysaccharide-induced liver injury and inflammation by modulating necroptosis and pyroptosis signaling pathways in piglets.

The liver plays crucial roles in material metabolism and immune response. Bacterial endotoxin can cause various liver diseases, thereby causing significant economic losses to pig industry. Tryptophan is an essential amino acid in piglets. However, whether tryptophan can alleviate liver injury and inflammation by regulating necroptosis and pyroptosis has not been clarified. This study aimed to investigate whether dietary tryptophan can alleviate lipopolysaccharide (LPS)-induced liver injury in weaned piglets. 18 weaned piglets were randomly distributed to three treatments, each with 6 replicates: (1) control; (2) LPS-challenged control; (3) LPS + 0.2% tryptophan. After feeding with control or 0.2% tryptophan-supplemented diets for 35 d, pigs were intraperitoneally injected with saline or LPS (100 mg/kg body weight). At 4 h post-injection, blood samples and liver were collected. Results indicated that tryptophan reduced alanine aminotransferase, aspartate aminotransferase, decreased the mRNA expression and protein expression of 70-kDa heat shock proteins. Moreover, tryptophan increased the mRNA expression and protein expression of claudin-1, occludin and zonula occludens and decreased hydrogen peroxide and malondialdehyde contents, and increased catalase, glutathione peroxidase and total superoxide dismutase activities and proinflammatory cytokine levels in the liver. Meanwhile, tryptophan inhibited pyroptosis-related and necroptosis-related protein expression in liver. Collectively, tryptophan could relieve liver damage, increased the antioxidant capacity and reduced inflammation by inhibiting pyroptosis and necroptosis signaling pathways.

Tryptophan alleviates intestinal damage through regulating necroptosis and TLR4/NOD signaling pathways in pigs after lipopolysaccharide challenge.

This study aimed to test the hypothesis that necroptosis, toll-like receptor 4 (TLR4)/nucleotide-binding oligomerization domain (NOD) signaling pathway in the jejunum of lipopolysaccharide (LPS)-challenged piglets are involved in the alleviation of intestinal injury and inflammation by tryptophan supplementation. Tryptophan supplementation has improved intestinal morphology. Also, tryptophan has been found to increase the mRNA and protein expression of tight junction proteins and decrease the expression of pro-inflammatory cytokines. Dietary tryptophan decreased the mRNA expression of heat shock protein 70, TLR4, NOD1, NOD2, myeloid differentiation primary response gene 88, interleukin 1 receptor-associated kinase 1, TNF receptor-associated factor 6, receptor-interacting serine/threonine-protein kinase 2-like, nuclear factor-kappaB transcription factor P65 in the jejunum of piglets. Tryptophan alleviated LPS-induced necroptosis and decreased the mRNA expression of mixed lineage kinase domain-like, receptor-interacting serine/threonine kinase 1, receptor-interacting serine/threonine-protein kinase 3-like, Fas (TNFRSF6)-associated via death domain, PGAM family member 5. Collectively, our results suggest that tryptophan supplementation helps in the attenuation of intestinal injury and inflammation by alleviating necroptosis and TLR4/NOD in lipopolysaccharide-challenged pigs.

Weekly versus triweekly cisplatin-alone adjuvant chemoradiotherapy after radical hysterectomy for stages IB-IIA cervical cancer with risk of recurrence.

Weekly and triweekly cisplatin-alone concomitant chemoradiotherapy regimens after radical surgery were compared in stages IB-IIA cervical cancer with intermediate- or high-risk factors to identify the better therapeutic regimen. We retrospectively analyzed patients with stages IB-IIA cervical cancer who received radical hysterectomy followed by concurrent adjuvant chemoradiotherapy to compare the efficiency between weekly and triweekly regimen groups. We evaluated between-group differences in survival, recurrence, compliance, and adverse effects. A total of 217 patients were included in this study (triweekly group vs. weekly group; 97 vs. 120). The mean follow-up was 47.2 months. The 5-year disease-free survival (DFS) was 84.4% or 76.5% for patients treated with triweekly cisplatin chemotherapy or the weekly regimen, respectively (P = 0.110). The 5-year overall survival (OS) was 82.4 and 78.6% for the same treatment groups, respectively (P = 0.540). The DFS of the patients with pelvic lymph node metastasis were marginally better in triweekly regimen group compared with the weekly group (P = 0.031). Grades 3-4 leukopenia was significantly more common in the triweekly group (P = 0.028). The weekly cisplatin chemotherapy group experienced the same therapeutic effect as the triweekly cisplatin-alone chemotherapy group but with less toxicity. However, triweekly cisplatin regimen reduced the recurrence in patients with pelvic lymph node metastasis.

TAZ promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells via the p-SMAD3.

OBJECTIVE: This study aims to offer insights about the biological influence of TAZ, which is a transcriptional coactivator containing a PDZ-binding motif, upon the apoptosis, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (h-PDLSCs). METHODS: We used the green fluorescence protein lentivirus infection system to knockdown or overexpress TAZ in h-PDLSCs. 5-ethynyl-2'-deoxyuridine (EdU) staining detected the proliferative activity, and h-PDLSC apoptosis was analyzed by Annexin V-APC staining. TAZ knockdown or overexpression was performed to determine the osteogenic differentiation function of TAZ during the osteogenic induction of h-PDLSCs. The molecular mechanism of TAZ in the promotion of h-PDLSC osteogenesis was also explored. The chemical inhibitor of SMAD2/3 SIS3 HCL was used to identify the effects in vitro osteogenic differentiation and bone formation in h-PDLSCs overexpressing TAZ. RESULTS: TAZ overexpression resulted in enhanced cell rapid multiplication, which increased the expression of messenger RNA in stemness-related genes. By comparison, TAZ knockdown reduced proliferative activity and increased the apoptosis of h-PDLSCs. After the 7-day osteogenic induction period, alkaline phosphatase activity in the TAZ-overexpression group was significantly increased, and mineralized nodules increased significantly after osteogenic induction for 21 days. Similarly, osteoblast differentiation of h-PDLSCs was impaired after TAZ knockdown. However, the osteogenic potential of the group exposed to the p-SMAD3 inhibitor was restored to its original level. CONCLUSION: Hippo/TAZ plays a positive role inside the proliferation, stemness maintenance, and osteogenic specialization of h-PDLSCs, and the specific downstream factor of osteogenic differentiation is SMAD3.

The Change of Systemic Immune-Inflammation Index Independently Predicts Survival of Colorectal Cancer Patients after Curative Resection.

BACKGROUND: The systemic immune-inflammation index (SII) has an important role in predicting survival in some solid tumors. However, little information is available concerning the change of the SII (∆SII) in colorectal cancer (CRC) after curative resection. This study was designed to evaluate the role of ∆SII in CRC patients who received surgery. METHODS: A total 206 patients were enrolled in this study. Clinicopathologic characteristics and survival were assessed. The relationships between overall survival (OS), disease-free survival (DFS), and ∆SII were analyzed with both univariate Kaplan-Meier and multivariate Cox regression methods. RESULTS: Based on the patient data, the receiver operating characteristic (ROC) optimal cutoff value of ∆SII was 127.7 for OS prediction. The 3-year and 5-year OS rates, respectively, were 60.4% and 36.7% in the high-∆SII group (>127.7) and 87.6% and 79.8% in the low-∆SII group (≤127.7). The 3-year and 5-year DFS rates, respectively, were 54.1% and 34.1% in the high-∆SII group and 80.3% and 78.5% in the low-∆SII group. In the univariate analysis, smoking, pathological stages III-IV, high-middle degree of differentiation, lymphatic invasion, vascular invasion, and the high-ΔSII group were associated with poor OS. Adjuvant therapy, pathological stages III-IV, vascular invasion, and ΔSII were able to predict DFS. Multivariate analysis revealed that pathological stages III-IV (HR = 0.442, 95% CI = 0.236-0.827, p = 0.011), vascular invasion (HR = 2.182, 95% CI = 1.243-3.829, p = 0.007), and the high-ΔSII group (HR = 4.301, 95% CI = 2.517-7.350, p < 0.001) were independent predictors for OS. Adjuvant therapy (HR = 0.415, 95% CI = 0.250-0.687, p = 0.001), vascular invasion (HR = 3.305, 95% CI = 1.944-5.620, p < 0.001), and the high-ΔSII group (HR = 4.924, 95% CI = 2.992-8.102, p < 0.001) were significant prognostic factors for DFS. CONCLUSIONS: The present study demonstrated that ∆SII was associated with the clinical outcome in CRC patients undergoing curative resection, supporting the role of ∆SII as a prognostic biomarker.

Reusable Mesh Signature Scheme for Protecting Identity Privacy of IoT Devices.

The development of the Internet of Things (IoT) plays a very important role for processing data at the edge of a network. Therefore, it is very important to protect the privacy of IoT devices when these devices process and transfer data. A mesh signature (MS) is a useful cryptographic tool, which makes a signer sign any message anonymously. As a result, the signer can hide his specific identity information to the mesh signature, namely his identifying information (such as personal public key) may be hidden to a list of tuples that consist of public key and message. Therefore, we propose an improved mesh signature scheme for IoT devices in this paper. The IoT devices seen as the signers may sign their publishing data through our proposed mesh signature scheme, and their specific identities can be hidden to a list of possible signers. Additionally, mesh signature consists of some atomic signatures, where the atomic signatures can be reusable. Therefore, for a large amount of data published by the IoT devices, the atomic signatures on the same data can be reusable so as to decrease the number of signatures generated by the IoT devices in our proposed scheme. Compared with the original mesh signature scheme, the proposed scheme has less computational costs on generating final mesh signature and signature verification. Since atomic signatures are reusable, the proposed scheme has more advantages on generating final mesh signature by reconstructing atomic signatures. Furthermore, according to our experiment, when the proposed scheme generates a mesh signature on 10 MB message, the memory consumption is only about 200 KB. Therefore, it is feasible that the proposed scheme is used to protect the identity privacy of IoT devices.

Improved Performance of SRAM-Based True Random Number Generator by Leveraging Irradiation Exposure.

Encryption is an important step for secure data transmission, and a true random number generator (TRNG) is a key building block in many encryption algorithms. Static random-access memory (SRAM) chips can be easily available sources of true random numbers, benefiting from noisy SRAM cells whose start-up values flip between different power-on cycles. Embarking from this phenomenon, a novel performance (i.e., randomness and throughput) improvement method of SRAM-based TRNG is proposed, and its implementation can be divided into two phases: irradiation exposure and hardware postprocessing. As the randomness of original SRAM power-on values is fairly low, ionization irradiation is utilized to enhance its randomness, and the min-entropy can increase from about 0.03 to above 0.7 in the total ionizing irradiation (TID) experiments. Additionally, while the data remanence effect hampers obtaining random bitstreams with high speed, the ionization irradiation can also weaken this impact and improve the throughput of TRNG. In the hardware postprocessing stage, Secure Hash Algorithm 256 (SHA-256) is implemented on a Field Programmable Gate Array (FPGA) with clock frequency of 200 MHz. It can generate National Institute of Standards and Technology (NIST) SP 800-22 compatible true random bitstreams with throughput of 178 Mbps utilizing SRAM chip with 1 Mbit memory capacity. Furthermore, according to different application scenarios, the throughput can be widely scalable by adjusting clock frequency and SRAM memory capacity, which makes the novel TRNG design applicable for various Internet of Things (IOT) devices.

The prognostic value of excission repair cross-complementation group one enzyme expression in locally advanced cervical carcinoma patients treated with cisplatin-based treatment: a meta-analysis.

BACKGROUND: Recently, several studies observed that locally advanced cervical carcinoma with negative excision repair crross-complementation group one enzyme expression has better outcomes in cisplatin-based chemotherapy or chemoradiotherapy than carcinoma with positive excission repair cross-complementation group one enzyme expression. In this meta-analysis, we quantitatively evaluated the prognostic value of excission repair cross-complementation group one enzyme expression in locally advanced cervical carcinoma patients receiving platinum-based chemotherapy or chemoradiotherapy. MATERIALS: A systematic search for relevant studies was conducted in the PubMed, Cochrane Library, EMBASE and Medline databases. Fixed- or random-effects models were used for pooled analysis. The endpoints were overall survival and disease-free survival () reported as ORs and 95% CIs. The effects of excission repair cross-complementation group one enzyme expression on the clinicopathological parameters were measured by the pooled ORs and their 95% CIs. RESULTS: Eight studies (612 patients in total) satisfied the inclusion criteria. Negative/low excission repair cross-complementation group one enzyme expression was significantly associated with better overall survival (OR, 1.92; 95% CI, 1.22 to 3.05; P = 0.005) and disease-free survival (OR, 5.77; 95% CI, 1.90 to 17.54; P = 0.002). Additionally, there were significant associations between excission repair cross-complementation group one enzyme expression and lymph node metastasis (OR, 2.57; 95% CI, 1.28 to 5.16; P = 0.008). CONCLUSIONS: This meta-analysis suggested that pretreatment excission repair cross-complementation group one enzyme expression might be a useful biomarker to predict prognoses for locally advanced cervical carcinoma patients receiving platinum-based chemotherapy or chemoradiotherapy.

Prognostic Value of Serum Lactate Dehydrogenase in Patients with Nasopharyngeal Carcinoma: a Meta-Analysis.

BACKGROUND: Serum-lactate dehydrogenase (S-LDH) is reported to be associated with poor survival in patients with nasopharyngeal carcinoma (NPC); however, the results are inconsistent. The aim of the study was to perform a meta-analysis to evaluate the prognostic value of S-LDH in patients with NPC. METHODS: PubMed and Web of Science were searched for relevant studies, and the fixed-effects model was employed to pool the hazard risks (HRs) from individual studies when no substantial heterogeneity was detected; otherwise, the random-effects model was used. Heterogeneity and publication bias were also analyzed. RESULTS: A total of 18 studies involving 13,789 patients were included in the meta-analysis, serum LDH level was associated with worse outcome in NPC patients. The combined HR for overall survival (OS) was 1.86 (95% confidence interval [CI]: 1.66 - 2.08; p < 0.01), and the pooled HRs for disease-free survival (DFS), distant metastasisfree survival (DMFS), and distant local relapse-free survival (LRFS) were 1.64 (95% CI: 1.45 - 1.86), 2.64 (95% CI: 2.15 - 3.25), and 2.59 (95% CI: 1.74 - 3.87), respectively. CONCLUSIONS: Our results suggest that higher serum LDH level is associated with worse survival in patients with NPC, which is helpful for a personalized treatment strategy for NPC patients.

Exploiting Host-Guest Interactions for the Synthesis of a Rod-Rod Block Copolymer with Crystalline and Liquid-Crystalline Blocks.

By making use of the host-guest interactions between the host molecule tris-o-phenylenedioxycyclotriphosphazene (TPP) and the rod-coil block copolymer (BCP) poly(ethylene oxide)-block-poly(octyl 4'-octyloxy-2-vinylbiphenyl-4-carboxylate) (PEO-b-PVBP), the supramolecular rod-rod block copolymer P(EO@TPP)-b-PVBP was constructed. It consists of a crystalline segment P(EO@TPP) with a hexagonal crystalline structure and a columnar nematic liquid-crystalline segment (PVBP). As the PVBP segments arrange themselves as columnar nematic phases, the crystalline structure of the inclusion complex P(EO@TPP), which has a smaller diameter, is destroyed. The self-assembled nanostructure is thus clearly affected by the interplay between the two blocks. On the basis of wide- and small-angle X-ray scattering analysis, we conclude that the supramolecular rod-rod BCP can self-assemble into a cylinder-in-cylinder double hexagonal structure.

PYCR2, induced by c-Myc, promotes the invasiveness and metastasis of breast cancer by activating AKT signalling pathway.

BACKGROUND: Pyrroline-5-carboxylate reductase 2 (PYCR2) expression is aberrantly upregulated in colon cancer. However, the functions and underlying mechanisms of PYCR2 in breast cancer remain elusive. The primary objective of the present study was to elucidate the function of PYCR2 in breast cancer and investigate whether PYCR2 may be transcriptionally regulated by c-Myc to activate the AKT signaling pathway. METHODS: Immunohistochemical analysis was performed to examine the expression of PYCR2 in breast cancer and adjacent non-cancerous tissues. Western blot and RT-qPCR were utilized to detect PYCR2 expression in breast cancer cells. Cellular functionalities were evaluated through Transwell assays in vitro and lung metastasis formation assays in vivo. Moreover, the impact of PYCR2 on the activation of AKT signaling was determined through western blot and immunohistochemistry analysis. The transcriptional regulation of PYCR2 expression by c-Myc was evaluated via both western blot analysis and luciferase gene reporter assay. RESULTS: PYCR2 overexpression was noted in breast cancer. Silencing PYCR2 expression attenuated the invasive and metastatic abilities of breast cancer cells. Furthermore, the activation of the AKT signaling pathway is indispensable for the promotion of invasion and metastasis mediated by PYCR2. Lastly, the binding of c-Myc to the promoter sequence of PYCR2 resulted in the upregulation of PYCR2 transcription. CONCLUSION: Taken together, these results indicate that PYCR2 is transcriptionally regulated by c-Myc and promotes invasion and metastasis in breast cancer through the activation of the AKT pathway.

A low noise capacitance to voltage readout circuit based on active feedback charge sensitive amplifier for micro-gyro.

Trans-impedance amplifier (TIA) based capacitance-voltage (C-V) readout circuits are widely used in micro-machined gyroscopes' control system. In this work, the noise performance of a TIA and charge sensitive amplifier (CSA) based C-V readout circuit is analyzed in detail. The theoretical derivation and simulation experiments carried out in this paper show that the thermal noise of high value feedback resistors in TIA dominates the output noise of the circuit, while a CSA-based readout circuit can overcome this shortcoming. Then, a CSA-based C-V readout circuit is designed with a 1.8 V transistor on a 180 nm complementary metal-oxide-semiconductor. This C-V-based readout circuit occupies an area of 0.039 mm2, which is smaller than the area of a 0603 package resistor. When 1 V bias voltage (Vb) is added to the capacitors under test, the tested C-V gain of this circuit is as high as 225 dB, and the tested output noise of the circuit is less than 150 nV/Hz. Finally, the fabricated chip achieved a resolution of 840 zF/Hz at Vb as low as 1 V. This CSA-based C-V readout circuit has more advantages in terms of noise and area over the TIA circuit and is more suitable for integration into the interface integrated circuit for micro-gyroscopes.

ANOS1 accelerates the progression of esophageal cancer identified by multi-omic approaches.

To assess the role of ANOS1 in esophageal cancer (ESCA) progression, multi-omic analysis and experimental validation were employed. It was revealed that ANOS1 expression is significantly enhanced in ESCA patients and cell lines. The expression level of ANOS1 in ESCA patients can distinguish the malignancy from normal tissue with an area under curve (AUC) >0.75. Moreover, increased expression of ANOS1 is associated with advanced T stage and worse disease-free survival of ESCA patients. Therefore, a clinically applicable nomogram with ANOS1 was established with strong predictive power. Furthermore, high expression of ANOS1 in ESCA is correlated with (i) the enrichment of epithelial-mesenchymal transition by gene set enrichment analysis, (ii) the involvement in hypoxia, angiogenesis, WNT signaling pathway, and TGFß signaling pathway by gene set variation analysis, (iii) the presence of the small insertion and deletion mutational signature ID9, associated with chromothripsis, in the single-nucleotide polymorphism analysis, (iv) the amplification of 11q13.3 in the copy number variants analysis, (v) the enrichment of cancer-associated fibroblasts and mesenchymal stromal cells in the tumor microenvironment. All the results from multi-omic analysis indicate that ANOS1 plays a pivotal role in accelerating the progression of ESCA. Results from in vivo and in vitro experiments show that the knockdown of ANOS1 hampers the proliferation of ESCA cells, further validating the oncogenic role of ANOS1 in ESCA. Additionally, potential chemotherapeutics with sensitivity were identified in the high-ANOS1 group. In conclusion, ANOS1 accelerates the progression of ESCA.

X-ray-downregulated nucleophosmin induces abnormal polarization by anchoring to G-actin.

Ionizing radiation poses significant risks to astronauts during deep space exploration. This study investigates the impact of radiation on nucleophosmin (NPM), a protein involved in DNA repair, cell cycle regulation, and proliferation. Using X-rays, a common space radiation, we found that radiation suppresses NPM expression. Knockdown of NPM increases DNA damage after irradiation, disrupts cell cycle distribution and enhances cellular radiosensitivity. Additionally, NPM interacts with globular actin (G-actin), affecting its translocation and centrosome binding during mitosis. These findings provide insights into the role of NPM in cellular processes in responding to radiation. This article enhances our comprehension of radiation-induced genomic instability and provides a foundational platform for prospective investigations within the realm of space radiation and its implications for cancer therapy.

Coarse- and Fine-Grained Fusion Hierarchical Network for Hole Filling in View Synthesis.

Depth image-based rendering (DIBR) techniques play an essential role in free-viewpoint videos (FVVs), which generate the virtual views from a reference 2D texture video and its associated depth information. However, the background regions occluded by the foreground in the reference view will be exposed in the synthesized view, resulting in obvious irregular holes in the synthesized view. To this end, this paper proposes a novel coarse and fine-grained fusion hierarchical network (CFFHNet) for hole filling, which fills the irregular holes produced by view synthesis using the spatial contextual correlations between the visible and hole regions. CFFHNet adopts recurrent calculation to learn the spatial contextual correlation, while the hierarchical structure and attention mechanism are introduced to guide the fine-grained fusion of cross-scale contextual features. To promote texture generation while maintaining fidelity, we equip CFFHNet with a two-stage framework involving an inference sub-network to generate the coarse synthetic result and a refinement sub-network for refinement. Meanwhile, to make the learned hole-filling model better adaptable and robust to the "foreground penetration" distortion, we trained CFFHNet by generating a batch of training samples by adding irregular holes to the foreground and background connection regions of high-quality images. Extensive experiments show the superiority of our CFFHNet over the current state-of-the-art DIBR methods. The source code will be available at https://github.com/wgc-vsfm/view-synthesis-CFFHNet.