ZNF692 drives malignant development of hepatocellular carcinoma cells by promoting ALDOA-dependent glycolysis.

Hepatocellular carcinoma (HCC) is one of the malignancies with the worst prognosis worldwide, in the occurrence and development of which glycolysis plays a central role. This study uncovered a mechanism by which ZNF692 regulates ALDOA-dependent glycolysis in HCC cells. RT-qPCR and western blotting were used to detect the expression of ZNF692, KAT5, and ALDOA in HCC cell lines and a normal liver cell line. The influences of transfection-induced alterations in the expression of ZNF692, KAT5, and ALDOA on the functions of HepG2 cells were detected by performing MTT, flow cytometry, Transwell, cell scratch, and colony formation assays, and the levels of glucose and lactate were determined using assay kits. ChIP and luciferase reporter assays were conducted to validate the binding of ZNF692 to the KAT5 promoter, and co-IP assays to detect the interaction between KAT5 and ALDOA and the acetylation of ALDOA. ZNF692, KAT5, and ALDOA were highly expressed in human HCC samples and cell lines, and their expression levels were positively correlated in HCC. ZNF692, ALDOA, or KAT5 knockdown inhibited glycolysis, proliferation, invasion, and migration and promoted apoptosis in HepG2 cells. ZNF692 bound to the KAT5 promoter and promoted its activity. ALDOA acetylation levels were elevated in HCC cell lines. KAT5 bound to ALDOA and catalyzed ALDOA acetylation. ALDOA or KAT5 overexpression in the same time of ZNF692 knockdown, compared to ZNF692 knockdown only, stimulated glycolysis, proliferation, invasion, and migration and reduced apoptosis in HepG2 cells. ZNF692 promotes the acetylation modification and protein expression of ALDOA by catalyzing KAT5 transcription, thereby accelerating glycolysis to drive HCC cell development.

Sex-Specific Variations in the mRNA Levels of Candidate Genes in Peripheral Blood Mononuclear Cells from Patients with Diabetes: A Multistep Study.

BACKGROUND: Type 2 diabetes (T2D) is one of the most prevalent diseases that also show sexual dimorphism in many different aspects. OBJECTIVES: This study aimed to distinguish the mRNA expression of genes in peripheral blood mononuclear cells (PBMCs) in men or women with T2D using a multistep analysis. METHODS: A total of 95 patients with T2D were compared based on their sex in terms of clinical variables and mRNA expression in their PBMCs. RESULTS: Men with T2D had lower LDLC, HDLC, and HbA1c values in their blood, but greater creatinine levels. In men with T2D, TLR4, CCR2, NOX2, and p67phox mRNA expression was greater, but IL6 and NF-κB mRNA expression was lesser in PBMCs. There was a link between fasting plasma glucose (FPG), triglycerides, and hs-CRP, as well as COX1 mRNA in men with T2D. In women with T2D, FPG was associated with the mRNA expression of THBS1 and p67phox, as well as triglycerides and HDLC levels. We found the exclusive effect of FPG on HDLC, HbA1c, as well as p67phox mRNA in PBMCs of women with T2D. Analysis revealed the exclusive effect of FPG on hs-CRP and PAFR mRNA in PBMCs of men with T2D. FPG was shown to be associated with body mass index, hs-CRP, triglycerides, and COX1 mRNA in men with T2D, and with serum triglycerides, THSB1, and p67phox mRNA in women with T2D, according to network analysis. HbA1c was linked with NF-κB mRNA in women with T2D. CONCLUSIONS: Using a multistep analysis, it was shown that network analysis outperformed traditional analytic techniques in identifying sex-specific alterations in mRNA gene expression in PBMCs of T2D patients. The development of sex-specific therapeutic approaches may result from an understanding of these disparities.

MRI-Conditional Eccentric-Tube Injection Needle: Design, Fabrication, and Animal Trial.

Effective radiation therapy aims to maximize the radiation dose delivered to the tumor while minimizing damage to the surrounding healthy tissues, which can be a challenging task when the tissue-tumor space is small. To eliminate the damage to healthy tissue, it is now possible to inject biocompatible hydrogels between cancerous targets and surrounding tissues to create a spacer pocket. Conventional methods have limitations in poor target visualization and device tracking. In this paper, we leverage our MR-tracking technique to develop a novel injection needle for hydrogel spacer deployment. Herein, we present the working principle and fabrication method, followed by benchtop validation in an agar phantom, and MRI-guided validation in tissue-mimic prostate phantom and sexually mature female swine. Animal trials indicated that the spacer pockets in the rectovaginal septum can be accurately visualized on T2-weighted MRI. The experimental results showed that the vaginal-rectal spacing was successfully increased by 12 ± 2 mm anterior-posterior.

Effect of wrist dorsiflexion on ultrasound-guided radial artery catheterisation using dynamic needle tip positioning technique in adult patients: a randomised controlled clinical trial.

BACKGROUND: It is generally recommended to keep the wrist joint mildly dorsiflexed during radial artery catheterisation. However, wrist dorsiflexion might decrease the success rate of radial artery catheterisation with dynamic needle tip positioning technique. Therefore, we assessed the success rates of two groups with or without wrist dorsiflexion by 5 cm wrist elevation in adult patients. METHODS: This randomised controlled clinical trial was performed between March and December 2018 in the First Affiliated Hospital of Shantou University Medical College, China. We recruited 120 adult patients undergoing major surgical procedures and randomly allocated them into two groups: dorsiflexion group (group D) and neutral group (group N). The primary outcome was first-attempt success rates of two groups. Secondary outcomes were overall success rates within 5 min; numbers of insertion and cannulation attempts; overall catheterisation time; duration of localisation, insertion and cannulation; and complication rates of catheterisation. RESULTS: First-attempt success rate was 88.3% in group D and 81.7% in group N (p=0.444). The overall success rate within 5 min was 93.3% in group D compared with 90.0% in group N (p=0.743). Numbers of insertion and cannulation attempts, overall catheterisation time, duration of localisation and insertion, and complication rates did not show a significant difference between the two groups. Cannulation time was longer in group N (35.68 s) than that in group D (26.19 s; p<0.05). CONCLUSION: Wrist dorsiflexion may not be a necessity for ultrasound-guided radial artery catheterisation using dynamic needle tip positioning technique in adult patients. TRIAL REGISTRATION NUMBER: ChiCTR1800015262.

Evaluation of functionality for serine and threonine phosphorylation with different evolutionary ages in human and mouse.

BACKGROUND: Rapid evolution of phosphorylation sites could provide raw materials of natural selection to fit the environment by rewiring the regulation of signal pathways. However, a large part of phosphorylation sites was suggested to be non-functional. Although the new-arising phosphorylation sites with little functional implications prevailed in fungi, the evolutionary performance of vertebrate phosphorylation sites remained elusive. RESULTS: In this study, we evaluated the functionality of human and mouse phosphorylation sites by dividing them into old, median and young age groups based on the phylogeny of vertebrates. We found the sites in the old group were more likely to be functional and involved in signaling pathways than those in the young group. A smaller proportion of sites in the young group originated from aspartate/glutamate, which could restore the ancestral functions. In addition, both the phosphorylation level and breadth was increased with the evolutionary age. Similar to cases in fungi, these results implied that the newly emerged phosphorylation sites in vertebrates were also more likely to be non-functional, especially for serine and threonine phosphorylation in disordered regions. CONCLUSIONS: This study provided not only insights into the dynamics of phosphorylation evolution in vertebrates, but also new clues to identify the functional phosphorylation sites from massive noisy data.

Risk factors of bicycle traffic injury among middle school students in chaoshan rural areas of china.

BACKGROUND: Bicycle injuries are a leading cause of accidental death among children in the world, and bicycle-related injuries are also very common in China, thus to find out bicycle injury risk factors is imperative. This study aims to identify the cyclist-, bicycle- and road-related risk factors of bicycle injury, to develop health education programs as an intervention and to provide a scientific basis for establishing policies against bicycle injury. METHODS: We selected two middle schools randomly among seven schools in Chaoshan rural areas,where the main means of transportation for students from home to school was bicycle. The subjects were middle school students from 7th to 9th grades from Gucuo Middle School and Hefeng Middle School. Cyclists were surveyed through questionnaires about bicycle injury in the past 12 months. RESULTS: Multivariable logistic analysis showed that compared with a combination-type road、 motor lane and a non-intact road were both risk factors of bicycle injuries. This was followed by riding with fatigue, non-motor lane and inattentive riding. CONCLUSION: Bicycle injuries are frequent in China. Three risk factors on bicycle traffic injury among middle school students in Chaoshan rural areas of China were identified. This study provides important data to develop intervention strategies for China and other developing countries.

Effect of butorphanol-soaked nasal packing after endoscopic nasal surgery: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: This study was designed to investigate the effect of butorphanol-soaked nasal packing on analgesia and sleep quality in patients undergoing bilateral endoscopic nasal surgery. METHODS: Sixty-six patients were enrolled and randomly allocated into three groups: group B1 (butorphanol 0.03mg/kg), group B2 (butorphanol 0.04mg/kg) and group N (control group). The primary outcome was postoperative pain scores evaluated by a Visual Analogue Scale (VAS) at 2h (T1), 8h (T2), 24h (T3) and 48h (T4) after surgery. Secondary outcome was postoperative sleep quality measured using Subjective Sleep Quality Value (SSQV). RESULTS: Postoperative VAS scores of butorphanol groups were significantly lower than the control group at T2, T3 and T4. VAS scores at each time point did not differ between groups B1 and B2. On the first and second nights after surgery, SSQV was higher in butorphanol groups than in the control group. There were no significant differences in SSQV1 and SSQV2 between group B1 and group B2. The incidence of respiratory depression, dizziness, agitation and rescue analgesic use did not show difference among three groups. CONCLUSIONS: Butorphanol-soaked nasal packing can reduce pain and improve sleep quality after bilateral endoscopic nasal surgery without increasing adverse effects. A concentration of 0.03mg/kg may be appropriate for clinical application. LEVEL OF EVIDENCE: Level 1B.

Effect of Helicobacter Pylori Infection on Glucose Metabolism, Lipid Metabolism and Inflammatory Cytokines in Nonalcoholic Fatty Liver Disease Patients.

Objective: To probe into the influence of Helicobacter pylori (Hp) infection on glucose metabolism, lipid metabolism, and inflammatory cytokines in patients with nonalcoholic fatty liver disease (MASLD). Methods: A total of 140 MASLD patients admitted to our Hospital between June 2020 and May 2021 were selected as the research objects. Based on the presence or absence of Hp infection, they were divided into the study group (73 cases with infection) and control group (67 cases without infection). Glucose metabolism indicators [fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), fasting insulin (FINS), glycated hemoglobin (HbAlc)], lipid metabolism indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], and inflammatory indicators [interleukin-37 (IL-37), interleukin-18 (IL-18)] were measured and compared between the two groups. Results: In terms of glucose metabolism indicators, the study group exhibited higher levels of FBG (5.84±0.49 vs 5.40±0.51, t=2.535, P=0.012), 2hPG (7.26±1.30 vs 6.50±1.53, t=3.321, P<0.001), and FINS (11.13±4.13 vs 9.12±3.72, t=3.224, P<0.001), and Insulin resistance index (HOMA-IR) (2.97±0.35 VS 2.13±0.54, t=3.761, P<0.001) and a lower level of HbAlc (5.25±0.56 vs 6.12±0.57, t=5.473, P<0.001) compared to the control group. Regarding lipid metabolism indicators, the study group exhibited higher levels of TC (5.64±1.49 vs 5.01±1.32, t=3.332, P<0.001), TG (1.89±0.34 vs 1.32±0.43, t=3.411, P<0.001), and LDL-C (3.31±0.43 vs 2.12±0.29, t=4.142, P<0.001), and a lower level of HDL-C (1.45±0.21 vs 1.78±0.42, t=4.347, P<0.001) compared to the control group. As for the inflammatory indicators, the study group exhibited higher levels of IL-37 (45.56±6.02 vs 34.02±3.28, t=9.332, P<0.001) and IL-18 (73.57±5.82 vs 60.34±4.84, t=10.141, P<0.001) compared to the control group. Conclusion: It is crucial to place appropriate emphasis on the impact of Hp infection on the glucose metabolism, lipid metabolism, and inflammatory response in MASLD patients, warranting careful consideration during the treatment of these patients.

Comparison of propofol-esketamine versus propofol for anesthesia in gastroscopy: a double-blind, randomized controlled clinical trial.

Objective: To compare the effects of propofol-esketamine and propofol in gastroscopy in adults. Methods: This randomized controlled clinical trial was performed from January 2021 to March 2021. Eighty patients were enrolled and allocated into normal saline group (group N) and esketamine group (group E). The primary outcome was total amount of propofol. Secondary outcomes included incidences of injection pain, involuntary movement, hemodynamic and respiratory adverse events during examination, total examination time, recovery time and postoperative adverse effects. Results: Total amount of propofol was significantly smaller in group E (101.64 ± 32.64 mg) than in group N (129.55 ± 36.34 mg, p = 0.001). Incidences of injection pain, involuntary movement and hypotension was significantly lower in group E than in group N. Incidences of hypertension and tachycardia was higher in group E than in group N. There was no significant difference in incidences of laryngospasm or hypoxemia, total examination time, recovery time, incidences of postoperative adverse effects between two groups. Conclusion: Combination of propofol with 0.2 mg/kg esketamine reduced total amount of propofol, provided a more stable hemodynamic status and did not affect recovery time in gastroscopy. Clinical trial registration: http://www.chictr.org, identifier ChiCTR2100042406.

Two dimensional semiconducting materials for ultimately scaled transistors.

Two dimensional (2D) semiconductors have been established as promising candidates to break through the short channel effect that existed in Si metal-oxide-semiconductor field-effect-transistor (MOSFET), owing to their unique atomically layered structure and dangling-bond-free surface. The last decade has witnessed the significant progress in the size scaling of 2D transistors by various approaches, in which the physical gate length of the transistors has shrank from micrometer to sub-one nanometer with superior performance, illustrating their potential as a replacement technology for Si MOSFETs. Here, we review state-of-the-art techniques to achieve ultra-scaled 2D transistors with novel configurations through the scaling of channel, gate, and contact length. We provide comprehensive views of the merits and drawbacks of the ultra-scaled 2D transistors by summarizing the relevant fabrication processes with the corresponding critical parameters achieved. Finally, we identify the key opportunities and challenges for integrating ultra-scaled 2D transistors in the next-generation heterogeneous circuitry.

Clinical Value of PPM1G Gene in Survival Prognosis and Immune Infiltration of Hepatocellular Carcinoma.

OBJECTIVE: Liver cancer is one of the most common malignancies, but its prognosis is still poor. Exploring potential biomarkers is an important direction of tumor research. We intend to use bioinformatics methods to explore potential biomarkers related to survival and prognosis of HCC. METHODS: The mRNA and protein expressions of PPM1G in liver cancer were analyzed by HPA, TIMER, and UALCAN databases, and the effects of PPM1G on the prognosis of liver cancer patients were explored by the GEPIA database. We also explored the correlation between PPM1G expression and liver cancer immune infiltration through the TIMER database and further explored the potential protein interaction network of PPM1G through the STRING database. RESULTS: The mRNA and protein expression of PPM1G gene in hepatocellular carcinoma tissues was lower than that in normal adjacent tissues. Liver cancer patients with high expression of PPM1G have a better prognosis than those with low expression of PPM1G. The expression of PPM1G is positively or negatively correlated with different immune cells of liver cancer, such as CD4+ T lymphocytes, CD8+ T lymphocytes, B cells, macrophages, and neutrophils. CONCLUSION: The liver cancer patients with high expression of PPM1G have a good prognosis, and PPM1G gene may be a potential immunotherapy target and prognostic marker of liver cancer.

MR-Conditional Actuations: A Review.

Magnetic resonance imaging (MRI) is one of the most prevailing technologies to enable noninvasive and radiation-free soft tissue imaging. Operating a robotic device under MRI guidance is an active research area that has the potential to provide efficient and precise surgical therapies. MR-conditional actuators that can safely drive these robotic devices without causing safety hazards or adversely affecting the image quality are crucial for the development of MR-guided robotic devices. This paper aims to summarize recent advances in actuation methods for MR-guided robots and each MR-conditional actuator was reviewed based on its working principles, construction materials, the noteworthy features, and corresponding robotic application systems, if any. Primary characteristics, such as torque, force, accuracy, and signal-to-noise ratio (SNR) variation due to the variance of the actuator, are also covered. This paper concludes with a perspective on the current development and future of MR-conditional actuators.

Genome assembly and transcriptome analysis provide insights into the antischistosome mechanism of Microtus fortis.

Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection. However, the underlying molecular mechanisms of this resistance are not yet known. Here, we perform the first de novo genome assembly of M. fortis, comprehensive gene annotation analysis, and evolution analysis. Furthermore, we compare the recovery rate of schistosomes, pathological changes, and liver transcriptomes between M. fortis and mice at different time points after infection. We observe that the time and type of immune response in M. fortis are different from those in mice. M. fortis activates immune and inflammatory responses on the 10th day post infection, such as leukocyte extravasation, antibody activation, Fc-gamma receptor-mediated phagocytosis, and the interferon signaling cascade, which play important roles in preventing the development of schistosomes. In contrast, an intense immune response occurrs in mice at the late stages of infection and could not eliminate schistosomes. Infected mice suffer severe pathological injury and continuous decreases in cell cycle, lipid metabolism, and other functions. Our findings offer new insights into the intrinsic resistance mechanism of M. fortis against schistosome infection. The genome sequence also provides the basis for future studies of other important traits in M. fortis.

Effect of butorphanol-soaked nasal packing after endoscopic nasal surgery: a double-blind, randomized, placebo-controlled trial

Abstract Objective This study was designed to investigate the effect of butorphanol-soaked nasal packing on analgesia and sleep quality in patients undergoing bilateral endoscopic nasal surgery. Methods Sixty-six patients were enrolled and randomly allocated into three groups: group B1 (butorphanol 0.03 mg/kg), group B2 (butorphanol 0.04 mg/kg) and group N (control group). The primary outcome was postoperative pain scores evaluated by a Visual Analogue Scale (VAS) at 2 h (T1), 8 h (T2), 24 h (T3) and 48 h (T4) after surgery. Secondary outcome was postoperative sleep quality measured using Subjective Sleep Quality Value (SSQV). Results Postoperative VAS scores of butorphanol groups were significantly lower than the control group at T2, T3 and T4. VAS scores at each time point did not differ between groups B1 and B2. On the first and second nights after surgery, SSQV was higher in butorphanol groups than in the control group. There were no significant differences in SSQV1 and SSQV2 between group B1 and group B2. The incidence of respiratory depression, dizziness, agitation and rescue analgesic use did not show difference among three groups. Conclusions Butorphanol-soaked nasal packing can reduce pain and improve sleep quality after bilateral endoscopic nasal surgery without increasing adverse effects. A concentration of 0.03 mg/kg may be appropriate for clinical application. Level of Evidence Level 1B.

RabGTD: a comprehensive database of rabbit genome and transcriptome.

The rabbit is a very important species for both biomedical research and agriculture animal breeding. They are not only the most-used experimental animals for the production of antibodies, but also widely used for studying a variety of human diseases. Here we developed RabGTD, the first comprehensive rabbit database containing both genome and transcriptome data generated by next-generation sequencing. Genomic variations coming from 79 samples were identified and annotated, including 33 samples of wild rabbits and 46 samples of domestic rabbits with diverse populations. Gene expression profiles of 86 tissue samples were complied, including those from the most commonly used models for hyperlipidemia and atherosclerosis. RabGTD is a web-based and open-access resource, which also provides convenient functions and friendly interfaces of searching, browsing and downloading for users to explore the big data.Database URL: http://www.picb.ac.cn/RabGTD/.

Systematic analysis reveals molecular characteristics of ERG-negative prostate cancer.

The TMPRSS2:ERG gene fusion is the most prevalent early driver gene activation in prostate cancers of European ancestry, while the fusion frequency is much lower in Africans and Asians. The genomic characteristics and mechanisms for patients lacking ERG fusion are still unclear. In this study, we systematically compared the characteristics of gene fusions, somatic mutations, copy number alterations and gene expression signatures between 201 ERG fusion positive and 296 ERG fusion negative prostate cancer samples. Both common and group-specific genomic alterations were observed, suggesting shared and different mechanisms of carcinogenesis in prostate cancer samples with or without ERG fusion. The genomic alteration patterns detected in ERG-negative group showed similarities with 77.5% of tumor samples of African American patients. These results emphasize that genomic and gene expression features of the ERG-negative group may provide a reference for populations with lower ERG fusion frequency. While the overall expression patterns were comparable between ERG-negative and ERG-positive tumors, we found that genomic alterations could affect the same pathway through distinct genes in the same pathway in both groups of tumor types. Altogether, the genomic and molecular characteristics revealed in our study may provide new opportunities for molecular stratification of ERG-negative prostate cancers.

Prioritizing functional phosphorylation sites based on multiple feature integration.

Protein phosphorylation is an important type of post-translational modification that is involved in a variety of biological activities. Most phosphorylation events occur on serine, threonine and tyrosine residues in eukaryotes. In recent years, many phosphorylation sites have been identified as a result of advances in mass-spectrometric techniques. However, a large percentage of phosphorylation sites may be non-functional. Systematically prioritizing functional sites from a large number of phosphorylation sites will be increasingly important for the study of their biological roles. This study focused on exploring the intrinsic features of functional phosphorylation sites to predict whether a phosphosite is likely to be functional. We found significant differences in the distribution of evolutionary conservation, kinase association, disorder score, and secondary structure between known functional and background phosphorylation datasets. We built four different types of classifiers based on the most representative features and found that their performances were similar. We also prioritized 213,837 human phosphorylation sites from a variety of phosphorylation databases, which will be helpful for subsequent functional studies. All predicted results are available for query and download on our website (Predict Functional Phosphosites, PFP, http://pfp.biosino.org/).