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Abstract Background Lipid metabolic reprogramming in colon cancer shows a potential impact on tumor immune microenvironment and is associated with response to immunotherapy. Therefore, this study aimed to develop a lipid metabolism-related prognostic risk score (LMrisk) to provide new biomarkers and combination therapy strategies for colon cancer immunotherapy. Methods Differentially expressed lipid metabolism-related genes (LMGs) including cytochrome P450 (CYP) 19A1 were screened to construct LMrisk in TCGA colon cancer cohort. The LMrisk was then validated in three GEO datasets. The differences of immune cell infiltration and immunotherapy response between LMrisk subgroups were investigated via bioinformatic analysis. These results were comfirmed by in vitro coculture of colon cancer cells with peripheral blood mononuclear cells, human colon cancer tissue microarray analysis, multiplex immunofluorescence staining and mouse xenograft models of colon cancer. Results Six LMGs including CYP19A1, ALOXE3, FABP4, LRP2, SLCO1A2 and PPARGC1A were selected to establish the LMrisk. The LMrisk was positively correlated with the abundance of macrophages, carcinoma-associated fibroblasts (CAFs), endothelial cells and the levels of biomarkers for immunotherapeutic response including programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden and microsatellite instability, but negatively correlated with CD8+ T cell infiltration levels. CYP19A1 protein expression was an independent prognostic factor, and positively correlated with PD-L1 expression in human colon cancer tissues. Multiplex immunofluorescence analyses revealed that CYP19A1 protein expression was negatively correlated with CD8+ T cell infiltration, but positively correlated with the levels of tumor-associated macrophages, CAFs and endothelial cells. Importantly, CYP19A1 inhibition downregulated PD-L1, IL-6 and TGF-β levels through GPR30-AKT signaling, thereby enhancing CD8+ T cell-mediated antitumor immune response in vitro co-culture studies. CYP19A1 inhibition by letrozole or siRNA strengthened the anti-tumor immune response of CD8+ T cells, induced normalization of tumor blood vessels, and enhanced the efficacy of anti-PD-1 therapy in orthotopic and subcutaneous mouse colon cancer models. Conclusion A risk model based on lipid metabolism-related genes may predict prognosis and immunotherapeutic response in colon cancer. CYP19A1-catalyzed estrogen biosynthesis promotes vascular abnormality and inhibits CD8+ T cell function through the upregulation of PD-L1, IL-6 and TGF-β via GPR30-AKT signaling. CYP19A1 inhibition combined with PD-1 blockade represents a promising therapeutic strategy for colon cancer immunotherapy.

This study aimed to investigate the effects of tea polyphenol (TP), epigallocatechin gallate (EGCG), and their palmitic acid-modified derivatives palmitoyl-TP (pTP) and palmitoyl-EGCG (pEGCG) on the accumulation of N-nitrosamine and biogenic amines (BAs), residual nitrites, and lipid oxidation in Chinese sausages. The microorganisms, color, and texture properties of sausages were evaluated. TP, EGCG, pTP, or pEGCG significantly inhibited the accumulation of N-nitrosodimethylamine (NDMA) and BAs, residual nitrites, and lipid oxidation, but enhanced the redness, hardness, and chewiness of sausages. The concentration of NDMA in sausages was reduced by 58.11%, 63.51%, 36.49%, and 44.59%, respectively, after treatment with TP, EGCG, pTP, and pEGCG. Both EGCG and pEGCG exhibited excellent inhibitory effects on the predominant BAs, including putrescine, tyramine, cadaverine, histamine, and 2-phenylethylamine. Palmitoyl-EGCG was found to be the strongest inhibitor of lipid oxidation. Besides, the four antioxidants weakly affected the population of total aerobic bacteria and lactic acid bacteria but totally suppressed the growth of undesirable Enterobacteriaceae. The principal component and correlation analyses proved that BAs, nitrites, lipid oxidation, and microbiota were responsible for the formation of NDMA. The results indicated that palmitic acid-modified TPs and similar derivatives might serve as potential preservatives to improve the safety and quality of fermented meat products.

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. The WIIC-processed 4LG electrode demonstrated enhanced electrical properties and better optical performance, leading to improved device efficiency and reliability. Furthermore, our study revealed that the WIIC process not only improved the adhesion between 4LG and the substrate but also enhanced the compatibility and interfacial interactions, resulting in the superior performance of the smart window device. These findings suggest that 4LG with WIIC holds great promise as a transparent conductive electrode for flexible smart windows, offering a cost-effective and efficient alternative to conventional ITO electrodes.

A direct current magnetron sputtering (DCMS) system at room temperature was applied to deposit the Ti/TiN/TiCN films. In order to research the effect of the microstructure of the TiN/TiCN layer on the Ti/TiN/TiCN films, the deposition time ratio of the TiN/TiCN layer ranged from 28.57 to 200%, and the whole deposition time of the films and the deposition time of Ti layer were constant. In this work, the relationship between structure and mechanical properties of films were investigated. The research results showed that the composition and structure of the films only slightly changed, while the crystalline orientation of the TiCN layer was of significant variation with the deposition time of the TiN layer. It is shown that the adhesion strength and internal stresses were 18.6 ± 1.5 N and 140 MPa when the deposition time ratio was 50%. By adjusting the deposition time ratio, the films displayed significant improvement in tribological behaviors. The coefficients of friction (COF) for the films deposited under deposition time ratio of 50% were about only 0.139 when the value of COF was stabilized. This work can provide a good wear-resisting film prepared approach at room temperature.

This study aimed to investigate the situations of pornography use among male college students of China, to explore the addiction possibility for pornography use, and to study the associations between pornography use and reproductive hormone levels and semen quality. Five hundred sixty-eight participants met the inclusion criteria and finished all of the questionnaires and hormone level and semen parameter examinations. A majority of participants (except one) had pornography use experience, 94.2% participants started pornography use before college, and 95.9% participants reported they had masturbation experience when using pornography. Early contact to pornography, frequent pornography use, high amount of time spending on pornography use, and frequent masturbation during pornography use were correlated with addiction trends. Earlier pornography use was found to be associated with lower serum prolactin (PRL), follicle-stimulating hormone (FSH), and progesterone (Prog), as well as lower sperm concentration and total sperm count. Higher frequency of pornography use was associated with lower serum estrogen (E2). In conclusion, pornography use was common among male college students in China. Early contact, high frequent use, and high frequency of masturbation during pornography use could lead to addiction trends and aberrant reproductive hormone levels and semen quality.

Background: The efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition (EPN) and total parenteral nutrition (TPN) in preventing nosocomial infection (NI) in critically ill adults has been questioned. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) to evaluate and rank the effectiveness of these therapies on NI amongst critically ill adults.Methods: Four electronic databases were systematically searched up to June 30, 2019 for RCTs comparing the administration of probiotics, prebiotics, synbiotics, EPN and TPN in critically ill adults. The primary outcome was NI. The relative efficacy of all outcomes was determined by a Bayesian framework with random effects NMA. We estimated the odds ratio (OR) and mean difference (MD) and ranked the comparative effects of all regimens with the surface under the cumulative ranking probabilities. The study has been registered on PROSPERO (CRD42019147032).Results: Fifty-five RCTs (7,119 patients) were identified. Primary outcome showed that synbiotics had the best effect in preventing NI than EPN (OR 0.37; 95% CrI 0.22–0.61), probiotics followed (OR 0.52; 95% CrI 0.34–0.77), whereas TPN significantly increased NI (OR 2.29; 95% CrI 1.48–3.67). Subgroup analysis showed that TPN significantly increased NI in intensive care unit (ICU) patients (OR 1.57; 95% CrI 1.01–2.56) and severe acute pancreatitis (SAP) patients (OR 3.93; 95% CrI 1.74–9.15). Secondary outcomes showed that synbiotics were more effective in preventing hospital-acquired pneumonia (HAP) (OR 0.34; 95% CrI 0.11–0.85), catheter-related bloodstream infection (OR 0.08; 95% CrI 0.01–0.80), urinary tract infection (OR 0.27; 95% CrI 0.08–0.71) and sepsis (OR 0.34; 95% CrI 0.16–0.70) than EPN. Amongst the treatments, probiotics were most effective for shortening the mechanical ventilation duration (MD −3.93; 95% CrI −7.98 to −0.02), prebiotics were most effective for preventing diarrhea (OR 0.24; 95% CrI 0.05–0.94) and TPN was the least effective in shortening hospital length of stay (MD 4.23; 95% CrI 0.97–7.33).Conclusions: Amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients.Take-Home Message: Nosocomial infection is a leading cause of mortality in critically ill patients in the ICU. However, the efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition and total parenteral nutrition in preventing nosocomial infection in critically ill adults has been questioned. The network meta-analysis provides evidence that amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients. The results of this study will provide a new scientific basis and a new idea for the debate on the efficacy of synbiotics and other treatments in the improvement of prognosis in critically ill adult patients.Tweet: Synbiotic prevents nosocomial infection in critically ill adults, while total parenteral nutrition has the adverse curative.

Basal p53 levels are tightly suppressed under normal conditions. Disrupting this regulation results in elevated p53 levels to induce cell cycle arrest, apoptosis, and tumor suppression. Here, we report the suppression of basal p53 levels by a nuclear, p53-regulated long noncoding RNA that we termed PURPL (p53 upregulated regulator of p53 levels). Targeted depletion of PURPL in colorectal cancer cells results in elevated basal p53 levels and induces growth defects in cell culture and in mouse xenografts. PURPL associates with MYBBP1A, a protein that binds to and stabilizes p53, and inhibits the formation of the p53-MYBBP1A complex. In the absence of PURPL, MYBBP1A interacts with and stabilizes p53. Silencing MYBBP1A significantly rescues basal p53 levels and proliferation in PURPL-deficient cells, suggesting that MYBBP1A mediates the effect of PURPL in regulating p53. These results reveal a p53-PURPL auto-regulatory feedback loop and demonstrate a role for PURPL in maintaining basal p53 levels.

Abstract Laparoscopic experience and relevant reports about PD catheter emplacement in Chinese patients are seldom. In this study, we described our experience with advanced laparoscopy for PD catheter implantation in Chinese patients. There were one hundred and thirty Chinese patients accepted advanced laparoscopic approach for PD catheter emplacement in this study. Six of 26 patients with prior abdominal operations had abdominal adhesion, while six of 104 patients without prior abdominal surgeries showed abdominal adhesion. Operation time required 10 to 180 minutes. During a mean follow-up time of 26.46 months, the catheter complications were shown as outflow obstruction (n = 6, 4.62%), pericatheter leaking (n = 3, 2.31%), hydrocele of tunica vaginalis (n = 1, 0.77% in all), and umbilical hernia (n = 2, 1.54%). Cumulative revision-free survival probability for catheter loss from mechanical complications at 8 years was 0.95. During the postoperative follow-up ranged between 6 and 106 months, 98 patients (75.38%) were still on CAPD, 17 patients (13.08%) died, 8 patients (6.15%) were transferred to hemodialysis, 6 patients (4.62%) received kidney transplantation, and 1 patient (0.77%) showed improved renal function. These results showed that PD catheter placement with advanced laparoscopy is a safe and effective approach in Chinese patients with or without prior abdominal surgeries.

Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a prosurvival function in human colorectal cancer cells (CRC) in vitro and tumor growth in vivo. Targeted deletion of PINCR in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. PINCR regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including BTG2, RRM2B and GPX1. Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR, we show that PINCR associates with the enhancer region of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/PINCR/Matrin 3 axis in response to DNA damage in CRC cells.

Sertoli cells (SCs) in the testes provide physical and nutritional support to germ cells. The vimentin cytoskeleton in SCs is disrupted by dibutyl phthalate (DBP), which leads to SCs dysfunction. In a previous study, we found that peroxisome proliferator-activated receptor alpha (PPARα) influenced the distribution of vimentin by affecting its phosphorylation in DBP-exposed SCs. In the present study, we investigated the role of Smad2/3 in regulating the expression of vimentin in DBP-exposed SCs. We hypothesized that Smad2/3 affects the distribution of vimentin by regulating its expression and that there is cross talk between Smad2/3 and PPARα. The real-time PCR and ChIP-qPCR results showed that SB431542 (an inhibitor of Smad2/3) could significantly attenuate the expression of vimentin induced by DBP in SCs. Phosphorylated and soluble vimentin were both downregulated by SB431542 pretreatment. WY14643 (an agonist of PPARα) pretreatment stimulated, while GW6471 (an antagonist of PPARα) inhibited, the activity of Smad2/3; SB431542 pretreatment also inhibited the activity of PPARα, but it did not rescue the DBP-induced collapse in vimentin. Our results suggest that, in addition to promoting the phosphorylation of vimentin, DBP also stimulates the expression of vimentin by activating Smad2/3 in SCs and thereby induces irregular vimentin distribution.

The incidence rate of infection by multidrug-resistant organisms (MDROs) can affect the accuracy of etiological diagnosis when using American Thoracic Society (ATS) guidelines. We determined the accuracy of the ATS guidelines in predicting infection or colonization by MDROs over 18 months at a single ICU in eastern China.This prospective observational study examined consecutive patients who were admitted to an intensive care unit (ICU) in Nanjing, China. MDROs were defined as bacteria that were resistant to at least three antimicrobial classes, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Pseudomonas aeruginosa, Acinetobacter baumannii. Screening for MDROs was performed at ICU admission and discharge. Risk factors for infection or colonization with MDROs were recorded, and the accuracy of the ATS guidelines in predicting infection or colonization with MDROs was documented.There were 610 patients, 225 (37%) of whom were colonized or infected with MDROs at ICU admission, and this increased to 311 (51%) at discharge. At admission, the sensitivity (70.0%), specificity (31.6%), positive predictive value (38.2%), and negative predictive value (63.5%), all based on ATS guidelines for infection or colonization with MDROs were low. The negative predictive value was greater in patients from departments with MDRO infection rates of 31-40% than in patients from departments with MDRO infection rates of 30% or less and from departments with MDRO infection rates more than 40%.ATS criteria were not reliable in predicting infection or colonization with MDROs in our ICU. The negative predictive value was greater in patients from departments with intermediate rates of MDRO infection than in patients from departments with low or high rates of MDRO infection.ClinicalTrials.gov NCT01667991.

Autohemotherapy is a commonly used treatment for recalcitrant chronic urticaria in some countries. Herein we report our experience using autologous serum therapy in eight patients with recalcitrant chronic spontaneous urticaria. Autologous serum therapy was initiated weekly for nine weeks followed by every fortnightly. Urticaria Activity Score (UAS) 7, Dermatology Life Quality Index (DLQI), and reduction of antihistamine usage were used to assess the treatment response. Eight patients (age range: 25–76 years old; four females and four males) had one to ten years of duration of recalcitrant chronic spontaneous urticaria. All failed to respond to high doses of second-generation antihistamines and five to immune-modulating agents. Three did not respond to omalizumab. At week nine, the reduction of UAS7 ranged from 76.2% to 100%. There was more than an 80% improvement in DLQI in all patients. The number of wheals seemed to be reduced first followed by pruritus. Three patients had stopped antihistamines by week eight of treatment. No adverse events were reported in all eight patients. Autologous serum therapy may serve as an alternative treatment for recalcitrant chronic spontaneous urticaria. Apart from the practicality, which requires frequent clinic visits, venipuncture, and centrifugation, it is cheap and effective with minimal adverse events.

This paper presents a comprehensive investigation of the optimal design of an interior permanent magnet synchronous motor (IPMSM) for electric vehicles (EVs), utilizing the hybrid artificial bee colony algorithm–support vector machine (HAS) algorithm. The performance of the drive motor is a crucial determinant of the overall vehicle performance, particularly in EVs that rely solely on a motor for propulsion. In this context, interior permanent magnet synchronous motors (IPMSMs) offer a compelling choice due to their high torque density, wide speed range, superior efficiency, and robustness. However, accurate analysis of the nonlinear characteristics of IPMSMs necessitates finite element analysis, which can be time-consuming. Therefore, research into methods for deriving an optimal model with minimal computation is of significant importance. The HAS is a powerful multimodal optimization technique that is capable of exploring several optimal solutions. It enhances the navigation capability by combining the artificial bee colony algorithm (ABC) with the kernel support vector machine (KSVM). Specifically, the algorithm improves the search ability by optimizing the movement of bees in each region generated by the KSVM. Furthermore, hybridization with the Nelder–Mead method ensures accurate and quick convergence at pointers discovered in the ABC. To demonstrate the effectiveness of the proposed algorithm, this study compared its performance with a conventional algorithm in two mathematical test functions, verifying its remarkable performance. Finally, the HAS algorithm was applied to the optimal design of the IPMSM for EVs. Overall, this paper provides a thorough investigation of the application of the HAS algorithm to the design of IPMSMs for electric vehicles, and its application is expected to benefit from the combination of machine-learning techniques with various other optimization algorithms. [ABSTRACT FROM AUTHOR]

Background Biological treatments are effective in the management of psoriasis. However, results in the real-world setting may differ from clinical trials. Objectives We aimed to evaluate the effectiveness of biological drugs among patients with psoriasis in Malaysia. Methods This was a retrospective review of adult patients on biologics who were notified to the Malaysian Psoriasis Registry between 2011 and 2019. Univariate and multivariate logistic regression was performed to identify factors associated with response to treatment in terms of the Psoriasis Area and Severity Index (PASI) 75, PASI 90, and Dermatology Life Quality Index (DLQI) 0/1. Results Of 130 patients, the most prescribed drug was ustekinumab (40.8%), followed by adalimumab (29.2%) and secukinumab (24.6%). Overall, the differences in the median PASI scores from baseline were −23.9 at 3–6 months, −25.8 at 12 months, and −27.8 at 3 years, while the difference in the median DLQI scores was −13.0 at 3–6 months. At 3–6 months, 57.6% achieved PASI-75, 32.9% achieved PASI-90, and 4.7% achieved PASI-100. These responses were sustained at 12 months and 3 years. Adalimumab was the most effective treatment with 88.9% achieving PASI-75, 77.8% PASI-90, and 22.2% PASI-100 at 3 years. However, secukinumab was more effective at achieving a PASI-100 response at 3–6 months (9.1%). Chinese or Indian ethnicity, concurrent use of systemic therapy or phototherapy, comorbidities, and a longer duration of psoriasis were associated with poorer response. Conclusion Biological treatments, particularly adalimumab and secukinumab, are effective in reducing disease severity and improving the quality of life of patients with psoriasis in Malaysia.

Aim: Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real‐world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population. Methods: This is an open‐labeled, multicenter, 4‐week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI‐SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs). Results: A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p <.05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug‐related AEs in the Asian population with cancer pain. Conclusion: This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831) [ABSTRACT FROM AUTHOR]