Patients with advanced cancer were treated with immune checkpoint inhibitors and injected with COVID-19 vaccine to improve their prognosis without increasing pancreatic related adverse events.

To investigate immune checkpoint inhibitors (ICIs) induced pancreatic injury (ICIPI), the prognostic effect of COVID-19 vaccine on cancer patients, and whether COVID-19 vaccine increases the incidence of ICIPI. We conducted a retrospective study of 256 stage IV cancer patients treated with ICIs at The First Affiliated Hospital of Anhui Medical University from January 2020 to November 2022. Data collected included pancreatic enzyme levels, treatment outcomes, and vaccination status. Statistical significance was determined using the χ2 test and Kaplan-Meier method (p < .05). Compared to the control group, the vaccinated group (p < .0001) and the group with elevated pancreatic enzyme levels (p = .044) demonstrated higher disease control rates, indicating a direct benefit of vaccination and enzyme monitoring on treatment outcomes. Additionally, vaccinated patients demonstrated longer overall survival versus unvaccinated patients (23.9 months [95% CI, 22.3-25.5] vs 23.6 months [95% CI, 21.1-26.2], HR = 0.45 [95% CI, 0.24-0.86], p = .015) and progression-free survival (17.2 months [95% CI, 14.3-20.1] vs 13.7 months [95% CI, 11.3-16.1], HR = 0.54 [95% CI, 0.36-0.82], p = .004). Importantly, the analysis revealed no significant association between vaccination and pancreatic injury (p = .46). Monitoring pancreatic enzymes can effectively evaluate the therapeutic impact in patients using ICIs. Patients vaccinated against COVID-19 experience better immunotherapy outcomes without an increased risk of ICIPI.

Associations of multi-human papillomavirus infections with expression of p16 in a cohort of women who underwent colposcopy: a retrospective study of 5165 patients.

Objective: Investigate HPV types in cervical specimens, their correlation with p16 expression in lesions, and diagnostic value for cervical lesions. Enhance clinical diagnosis reliability. Methods: Retrospective cross-sectional study at Fujian Maternity and Child Health Hospital's Cervical Disease Center (Jun 2019-Dec 2021). Patients with abnormal cervical screening underwent colposcopy and conization. Pathological diagnosis based on colposcopy, cervical biopsy, ECC, and conization. Analyzed HPV genotyping (18 HR-HPV, 5 LR-HPV) and p16 expression correlation. Statistical analysis used R software. Results: he expression of p16 is significantly associated with the infection of high-risk HPV types, such as 16, 33, 52, and 58, with an increased risk of 1.4 times or higher (OR=1.91, 3.14, 1.40, and 1.78, respectively). The risk of p16 expression increased 4-fold for multiple high-risk HPV types [adjusted OR (95% CI) = 4 (2.92~5.5), P-value <0.001]. Compared to the p16(-) group, the p16(+) group had a higher association with cervical lesions worse than HSIL (High-grade Squamous Intraepithelial Lesions).In the group with multiple Human Papillomavirus Infections with types 16, 33, 52, and 58, the risk of cervical lesions worse than HSIL increased by up to 660-fold compared to the negative group (adjusted OR=660.62, 95% CI: 91.39~4775.53, P<0.001), indicating that this combination of HPV types posed the greatest risk for cervical lesions above HSIL. Conclusions: p16 plays a crucial role in cervical lesion progression, linked to high-risk HPV. Combining p16 with HPV screening improves cervical cancer detection. Studying multiple HPV infections will enhance prevention and management.

Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection.

Influenza A virus (IAV) is a leading cause of human respiratory infections and poses a major public health concern. IAV replication can affect the expression of DNA methyltransferases (DNMTs), and the subsequent changes in DNA methylation regulate gene expression and may lead to abnormal gene transcription and translation, yet the underlying mechanisms of virus-induced epigenetic changes from DNA methylation and its role in virus-host interactions remain elusive. Here in this paper, we showed that DNMT1 expression could be suppressed following the inhibition of miR-142-5p or the PI3K/AKT signaling pathway during IAV infection, resulting in demethylation of the promotor region of the 2'-5'-oligoadenylate synthetase-like (OASL) protein and promotion of its expression in A549 cells. OASL expression enhanced RIG-I-mediated interferon induction and then suppressed replication of IAV. Our study elucidated an innate immunity mechanism by which up-regulation of OASL contributes to host antiviral responses via epigenetic modifications in IAV infection, which could provide important insights into the understanding of viral pathogenesis and host antiviral defense.

Generation and Characterization of a Replication-Competent Human Adenovirus Type 55 Encoding EGFP.

Human adenovirus 55 (HAdV-55) has recently caused outbreaks of acute respiratory disease (ARD), posing a significant public threat to civilians and military trainees. Efforts to develop antiviral inhibitors and quantify neutralizing antibodies require an experimental system to rapidly monitor viral infections, which can be achieved through the use of a plasmid that can produce an infectious virus. Here, we used a bacteria-mediated recombination approach to construct a full-length infectious cDNA clone, pAd55-FL, containing the whole genome of HadV-55. Then, the green fluorescent protein expression cassette was assembled into pAd55-FL to replace the E3 region to obtain a recombinant plasmid of pAd55-dE3-EGFP. The rescued recombinant virus rAdv55-dE3-EGFP is genetically stable and replicates similarly to the wild-type virus in cell culture. The virus rAdv55-dE3-EGFP can be used to quantify neutralizing antibody activity in sera samples, producing results in concordance with the cytopathic effect (CPE)-based microneutralization assay. Using an rAdv55-dE3-EGFP infection of A549 cells, we showed that the assay could be used for antiviral screening. Our findings suggest that the rAdv55-dE3-EGFP-based high-throughput assay provides a reliable tool for rapid neutralization testing and antiviral screening for HAdV-55.

Integration of cross-scale milli/microlenses by ion beam etching and femtosecond laser modification.

Integrated cross-scale milli/microlenses offer irreplaceable functions in modern integrated optics with the advantage of reducing the size of the optical system to millimeters or microns. However, the technologies for fabricating millimeter-scale lenses and microlenses are always incompatible, which makes the successful fabrication of cross-scale milli/microlenses with a controlled morphology challenging. Here, ion beam etching is proposed as a means to fabricate smooth millimeter-scale lenses on various hard materials. In addition, by combining femtosecond laser modification and ion beam etching, an integrated cross-scale concave milli/microlens (27,000 microlenses on a lens with a diameter of 2.5 mm) is demonstrated on fused silica, and can be used as the template for a compound eye. The results provide a new, to the best of our knowledge, route for the flexible fabrication of cross-scale optical components for modern integrated optical systems.

Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake.

Residual feed intake (RFI) is one of the indicators of feed efficiency. To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations.

Construction of flexible fiber-shaped boron-doped diamond film and its supercapacitor application.

Flexible fiber-shaped supercapacitors (FSSCs) are promising candidates as electrode materials for the development of deformable electronic devices. Although tremendous efforts have been focused on the preparation of flexible electrode materials, traditional FSSCs materials face problems of inferior stability and complicated processes. Boron-doped diamond (BDD) holds promise as a FSSC electrode, owing to its well-established preparation process, strong acid and alkali corrosion resistance, environmentally and skin-friendly characteristics. Here, we reported a novel strategy for the construction of BDD-based FSSCs by growing a BDD film on a flexible tantalum (Ta) fiber substrate through hot filament chemical vapor deposition technique. Results showed that the BDD fiber film featured 10 folds improvement in specific capacitance than a planar BDD electrode. A symmetric supercapacitor device was assembled using the BDD fiber electrode and achieved an energy density of 25.6 mJ cm-2 at a power density of 0.6 mW cm-2, and a desirable stability with higher capacitance retention of 93.5% after 20,000 cycles. Furthermore, the symmetric BDD fiber device exhibited satisfactory bendability with high specific capacitance retention under various bending deformations. The findings in this research work hold promise for the fabrication of high performance flexible FSSCs.

Identification and characterization of hypothalamic circular RNAs associated with bovine residual feed intake.

Residual feed intake (RFI) is crucial economic indicator used for calculating the feed efficiency of growing beef cattle. circRNA plays an important biological role in gene transcriptional regulation, but little is known about its potential functional regulation underlying RFI phenotypic variation. As the core center of regulation of animal feeding, the hypothalamus is closely associated with RFI. Therefore, the present study aimed to identify the key genes and functional pathways contributing to variance in cattle RFI phenotypes using RNA sequencing from hypothalamic tissue samples, in order to gain insight into the potential regulatory role of circRNAs in bovine RFI phenotypic variation. Differentially expressed genes were detected by RNA sequencing for beef cattle in the high and low RFI groups, followed by GO, KEGG enrichment, and circRNA-miRNA co-expression network analysis. A total of 257 circRNAs were differentially expressed between the two groups, with 128 significantly upregulated and 129 significantly downregulated genes in H group compared to L group. Among them, 9 unique circRNAs were present in group L and 4 unique circRNAs were present in group H. GO and KEGG enrichment analysis of the source genes of the differentially expressed circRNAs revealed that they were mainly involved in metabolic processes, such as cellular metabolic processes, cellular macromolecular metabolic processes, and regulatory pathways related to nutrient metabolism, including protein and amino acid metabolism, as well as vitamin metabolism and pancreatic secretion associated with the animal feeding behavior. The circRNAs detected in this study were mostly novel, and have not been investigated directly to be associated with the RFI phenotype. Interestingly, most miRNAs of differentially expressed circRNAs predicted based on the circRNA-miRNA co-expression network analysis by using top 50 differentially expressed circRNAs and 13 unique circRNAs, have been reported to be related to animal RFIs, implying that circRNAs in bovine hypothalamic tissue may regulate phenotypic variation in RFI through miRNAs. The study results illustrate the complex biological functions of the hypothalamus in regulating feed efficiency and showing the potential role of circRNAs in the feeding behavior regulation of livestock, which would contributing to expanding the understanding of circRNA.

The Effect of Inflammatory Markers on the Survival of Advanced Gastric Cancer Patients Who Underwent Anti-Programmed Death 1 Therapy.

PURPOSE: This clinical study sought to determine whether the levels of inflammatory markers predicted the survival of advanced gastric cancer (AGC) patients who underwent anti-programmed death 1 (PD-1) therapy. METHODS: Using AGC patient plasma samples and baseline characteristics, we investigated the specific value of inflammatory markers in AGC from a clinical perspective in immunotherapy. RESULTS: One hundred and six patients with AGC who underwent anti-PD-1 therapy were enrolled in this study between 20 July 2019 and 16 March 2021. A significant decrease in NLR, dNLR, and SII was noticed among the PR (P=0.023; P=0.036; P=0.001), SD (P=0.048; P=0.022; P=0.023), ORR (P=0.021; P=0.032; P=0.001), and DCR (P=0.003; P=0.001; P<0.001) groups after anti-PD-1 therapy. Additionally, a significant decline of PLR was also observed in PR (P=0.010), ORR (P=0.007), and DCR (P=0.005) after anti-PD-1 therapy. Only MLR levels increased significantly at the time of anti-PD-1 immunotherapy the failure compared to baseline (P=0.039). And statistically significant elevations in NLR (P=0.001), MLR (P=0.020), dNLR (P=0.002), and SII (P=0.019) were found in failure of anti-PD-1 treatment compared to optimal efficacy in AGC patients. In first-line treatment, the number of metastatic sites (P=0.001) was an independent prognostic factor for PFS, and peritoneal metastases (P=0.004) and platelet-to-lymphocyte ratio (PLR) level (P=0.014) were independent prognostic predictors of OS according to Cox regression analysis. In second-line or posterior treatment, the number of metastatic sites (P=0.007), ECOG (P=0.011), and PLR level (P=0.033) were independent prognostic factors for PFS in AGC patients, and the number of metastatic sites (P=0.003), differentiation (P=0.030), and NLR level (P<0.001) were independent prognostic factors for OS according to Cox regression analysis. CONCLUSIONS: NLR, PLR, MLR, dNLR, and SII can reflect the short-term efficacy of immunotherapy in patients who underwent anti-PD-1 therapy with AGC. PLR is an independent prognostic factor for OS in AGC patients receiving first-line immunotherapy and PFS in those receiving second-line or posterior immunotherapy. And NLR was an independent prognostic factor for OS in AGC patients receiving second-line or posterior immunotherapy. The number of metastatic sites was significantly associated with the prognosis of AGC patients who received immunotherapy.

A false alarm of COVID-19 pneumonia in lung cancer with anti-PD-1 related pneumonitis: a case report and review of the literature.

BACKGROUND: Pneumonitis belongs to the fatal toxicities of anti-PD-1/PD-L1 treatments. Its diagnosis is based on immunotherapeutic histories, clinical symptoms, and the computed tomography (CT) imaging. The radiological features were typically ground-glass opacities, similar to CT presentation of 2019 Novel Coronavirus (COVID-19) pneumonia. Thus, clinicians are cautious in differential diagnosis especially in COVID-19 epidemic areas. CASE PRESENTATION: Herein, we report a 67-year-old Han Chinese male patient presenting with dyspnea and normal body temperature on the 15th day of close contact with his son, who returned from Wuhan. He was diagnosed as advanced non-small cell lung cancer and developed pneumonitis post Sintilimab injection during COIVD-19 pandemic period. The chest CT indicated peripherally subpleural lattice opacities at the inferior right lung lobe and bilateral thoracic effusion. The swab samples were taken twice within 72 hours and real-time reverse-transcription polymerase-chain-reaction (RT-PCR) results were COVID-19 negative. The patient was thereafter treated with prednisolone and antibiotics for over 2 weeks. The suspicious lesion has almost absorbed according to CT imaging, consistent with prominently falling CRP level. The anti-PD-1 related pneumonitis mixed with bacterial infection was clinically diagnosed based on the laboratory and radiological evidences and good response to the prednisolone and antibiotics. CONCLUSION: The anti-PD-1 related pneumonitis and COVID-19 pneumonia possess similar clinical presentations and CT imaging features. Therefore, differential diagnosis depends on the epidemiological and immunotherapy histories, RT-PCR tests. The response to glucocorticoid is still controversial but helpful for the diagnosis.

Attempting AG-Doped Diamond-Like Carbon Film to Improve Seal Performance of Hydraulic Servo-Actuator.

A hydraulic servo-actuator is a critical aircraft control device whose sealing performance directly affects the sensitivity and accuracy of the aircraft flight attitude. Foreign intrusive particles in hydraulic oil may induce the vulnerable friction pair wear and the seal leak; they may even lead to oil spill accidents. This work attempts to conduct a systematical investigation of Ag-doped diamond-like carbon (Ag-DLC) film to improve the seal performance. The failure of the servo-actuator was analyzed. Then, a series of Ag-DLC films was deposited; the structure and combined tribological performances of the Ag-DLC films were investigated. The results show that the intensity of the Ag (111) crystal face in the films increases with an increase of Ag content. The hardness, intrinsic stress, frictional coefficient, and wear rate of the films tend to decrease with the amount of doping metal. The a:C-Ag10.5% film exhibits optimal combined properties. The Ag doping makes the film toughness improve; both soft Ag particles and a graphitized top layer act as solid lubricants. Our findings may offer a novel approach to make DLC film applicable for improving the seal performance of hydraulic servo-actuator. Based on the experimental data, a mechanism behind the film modification of Ag-DLC film is also revealed.

Prognostic value of DNA aneuploidy in gastric cancer: a meta-analysis of 3449 cases.

BACKGROUND: DNA aneuploidy has attracted growing interest in clinical practice. Nevertheless, its prognostic value in gastric cancer patients remains controversial. This meta-analysis aims to explore the impact of DNA ploidy status on the survival of gastric cancer patients. METHODS: We used PubMed and Web of Science databases to retrieve relevant articles. The correlation between DNA aneuploidy and the clinicopathological features of gastric cancer, such as stage, depth of invasion (T), lymph node metastasis (N), distant metastasis (M), differentiation (G), tumor types (Lauren classification) and overall survival (OS) were evaluated. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were collected carefully from each article OS was presented with HRs. The relationships between DNA aneuploidy and each characteristic were analyzed using risk ratios (RR) and a 95% confidence interval (CI). Significance was established using P < 0.05. Funnel plot was conducted to detect the publication bias. RESULTS: After careful selection, 25 studies involving 3449 cases were eligible for further analyses. Patients with DNA aneuploidy were considered at risk of more advanced stages (stage III-IV vs. stages I-II, RR = 1.23; 95% CI, 1.07 to 1.42; P = 0.003), lymph node metastasis (N+ vs. N-: RR = 1.43; 95% CI, 1.12 to 1.82, P = 0.004), and intestinal tumor type (intestinal vs. diffuse: RR = 1.45; 95% CI, 1.02 to 2.06; P = 0.04). And an adverse relation was observed between DNA aneuploidy and tumor differentiation. While no association was found between DNA aneuploidy and distant metastasis (P = 0.42) nor depth of tumor invasion (P = 0.86). Regarding overall survival, aneuploid tumors were associated with worse survival in all patients (P < 0.00001). CONCLUSIONS: We found that DNA aneuploidy was an important predictor for gastric cancer patients, and should be used as a potential biomarker for further classification in gastric cancer.

Methylation of DACT2 promotes papillary thyroid cancer metastasis by activating Wnt signaling.

Thyroid cancer is the most common endocrine malignant disease and the incidence is increasing. DACT2 was found frequently methylated in human lung cancer and hepatocellular carcinoma. To explore the epigenetic change and the role of DACT2 in thyroid cancer, 7 thyroid cancer cell lines, 10 cases of non-cancerous thyroid tissue samples and 99 cases of primary thyroid cancer samples were involved in this study. DACT2 was expressed and unmethylated in K1, SW579, FTC-133, TT, W3 and 8505C cell lines. Loss of expression and complete methylation was found in TPC-1 cells. Restoration of DACT2 expression was induced by 5-aza-2'deoxycytidine treatment. It demonstrates that the expression of DACT2 was regulated by promoter region methylation. In human primary papillary thyroid cancer, 64.6% (64/99) was methylated and methylation of DACT2 was related to lymph node metastasis (p<0.01). Re-expression of DACT2 suppresses cell proliferation, invasion and migration in TPC-1 cells. The activity of TCF/LEF was inhibited by DACT2 in wild-type or mutant ß-catenin cells. The activity of TCF/LEF was increased by co-transfecting DACT2 and Dvl2 in wild-type or mutant ß-catenin cells. Overexpression of wild-type ß-catenin promotes cell migration and invasion in DACT2 stably expressed cells. The expression of ß-catenin, c-myc, cyclinD1 and MMP-9 were decreased and the level of phosphorylated ß-catenin (p-ß-catenin) was increased after restoration of DACT2 expression in TPC-1 cells. The expression of ß-catenin, c-myc, cyclinD1 and MMP-9 were increased and the level of p-ß-catenin was reduced after knockdown of DACT2 in W3 and SW579 cells. These results suggest that DACT2 suppresses human papillary thyroid cancer growth and metastasis by inhibiting Wnt signaling. In conclusion, DACT2 is frequently methylated in papillary thyroid cancer. DACT2 expression was regulated by promoter region methylation. DACT2 suppresses papillary thyroid cancer proliferation and metastasis by inhibiting Wnt signaling.