Prognostic Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Acute Ischemic Stroke Patients After Thrombolysis.

Context: The neutrophil to lymphocyte ratio (NLR) or platelet to lymphocyte ratio (PLR) is an inflammation marker of acute ischemic stroke, but the predictive value of NLR and PLR before and after thrombolysis for short-term prognosis in acute ischemic stroke patients after thrombolysis remains largely obscure. This study attempts to clarify the predictive value of NLR and PLR before and after thrombolysis for short-term prognosis in acute ischemic stroke patients after thrombolysis. Design: A retrospective study was carried out in the Affiliated Hospital of Hangzhou Normal University involving 120 patients visiting the neurology department of our hospital from May 2019 to October 2022 and meeting the selection criteria. The participants were assigned to the good prognosis group and the poor prognosis group based on the modified Rankin scale score. Laboratory data collected include NLR and PLR at admission as well as NLR and PLR collected from venous blood within 24 h after thrombolysis. Results: Age, hyperlipidemia, atrial fibrillation, rheumatic heart disease, and National Institutes of Health Stroke Scale (NIHSS) scores after thrombolysis depicted statistical significance between both groups (P < .05). Hyperlipidemia, atrial fibrillation, and NIHSS scores before thrombolysis were independent risk elements for adverse prognosis (P < .05). NLR and PLR before and after thrombolysis in the poor prognosis group depicted an elevation relative to that in the good prognosis group (P < .05). The area under the curve of NLR or PLR predicting adverse prognosis after thrombolysis depicted an elevation relative to that before thrombolysis (P < .05). Conclusion: The predictive value of NLR and PLR post-thrombolysis for short-term prognosis in acute ischemic stroke patients depicts an elevation relative to pre-thrombolysis; our study provides effective predictive indicators for short-term prognosis in acute ischemic stroke patients.

The safety of not implementing endoscopic nasobiliary drainage after elective clearance of choledocholithiasis: a systematic review and meta-analysis.

BACKGROUND: Endoscopic nasobiliary drainage (ENBD) is used as a drainage technique in patients with choledocholithiasis after stone removal. However, ENBD can cause discomfort, displacement, and other complications. This study aims to evaluate the safety of not using ENBD following elective clearance of choledocholithiasis. METHODS: Relevant studies were identified by searching PubMed, Web of Science, EMBASE, EBSCO, and Cochrane Library from their inception until August 2023. The main outcomes assessed were postoperative complications and postoperative outcomes. Subgroup analyses were conducted based on study design types and treatment procedures. RESULTS: Six studies, including three randomized controlled trials (RCTs) and three cohort studies, were analyzed. Among these, four studies utilized endoscopic techniques, and two employed surgical methods for choledocholithiasis clearance. The statistical analysis showed no significant difference in postoperative complications between the no-ENBD and ENBD groups, including pancreatitis (RR: 1.55, p = 0.36), cholangitis (RR: 1.81, p = 0.09), and overall complications (RR: 1.25, p = 0.38). Regarding postoperative outcomes, the subgroup analysis indicated that the bilirubin normalization time was longer in the no-ENBD group compared to the ENBD group in RCTs (WMD: 0.24, p = 0.07) and endoscopy studies (WMD: 0.23, p = 0.005), although the former did not reach statistical difference. There was also no significant difference in the length of postoperative hospital stay between the groups (WMD: -0.30, p = 0.60). CONCLUSION: It appears safe to no- ENBD after elective clearance of choledocholithiasis.

The circZEB1/miR-337-3p/OGT axis mediates angiogenesis and metastasis via O-GlcNAcylation and up-regulating YBX1 in breast cancer.

Background: A growing corpus of research has revealed that circular RNAs (circRNAs) have become increasingly important for the growth of malignancies in recent years. CircRNAs as ideal candidates for breast cancer (BC) therapeutic targets is still absent. Methods: In our study, the dysregulated circRNAs in BC progression were explored, we analysed the BC's circRNA expression profiles using publicly available datasets (GSE101124 and GSE101122). The expression of circZEB1 in BC and cell lines was investigated by qPCR. RNase and actinomycin D were used to examine the features of circZEB1. The function of circZEB1 was subsequently investigated through the utilisation of colony formation, tube formation, transwell assays, and xenograft animal models.RNA immunoprecipitation (RIP), luciferase reporter assays, immunoprecipitation (co-IP) test in conjunction with LC-MS, and ChIP-seq assay to investigate the molecular mechanism underlying the biological activity of circZEB1 in BC. Results: Among the circRNAs, we were particularly interested in hsa_circ_0000228, which is spliced from the oncogene ZEB1. In BC cell lines, CircZEB1 expression was upregulated. CircZEB1 knockdown prevented BC cells from migrating and invading, as well as HUVECs from forming tubes and developing. By sponging miR-337-3p, functional testing revealed that circZEB1 promoted O-GlcNAcylation, increased YBX1, and OGT expression. Moreover, circZEB1 overexpression is reversible, in contrast to YBX1 knockdown, which mostly results in the downregulation of multiple oncogenes. Conclusion: Our study indicate that circZEB1 had oncogenic function in BC by focusing on circZEB1/miR-337-3p/OGT and YBX1. It might be inferred that circZEB1 could be a promising new target for BC treatment.

Risk of Hematologic Malignancies in Patients with Inflammatory Bowel Disease: A Meta-Analysis of Cohort Studies.

Background/Aims: Inflammatory bowel disease (IBD) may contribute to the development of hematologic malignancies. In this study, the potential relationship between IBD and hematologic malignancies was investigated. Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for all cohort studies comparing the incidence of hematologic malignancies in non-IBD populations with that in IBD patients, and we extracted relevant data from January 2000 to June 2023 for meta-analysis. Results: Twenty cohort studies involving 756,377 participants were included in this study. The results showed that compared with the non-IBD cohort, the incidence of hematologic malignancies in the IBD cohort was higher (standardized incidence ratio [SIR]=3.05, p<0.001). According to the specific types of IBD, compared with the non-IBD patients, the incidences of hematologic malignancies in ulcerative colitis patients (SIR=2.29, p=0.05) and Crohn's disease patients (SIR=3.56, p=0.005) were all higher. In the subgroup analysis of hematologic malignancy types, compared with the control group, the incidences of non-Hodgkin's lymphoma (SIR=1.70, p=0.01), Hodgkin's lymphoma (SIR=3.47, p=0.002), and leukemia (SIR=3.69, p<0.001) were all higher in the IBD cohort. Conclusions: The incidence of hematologic malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and leukemia is higher in patients with IBD (ulcerative colitis or Crohn's disease) than in non-IBD patients.

Effects of Metformin on CIMT and FMD in PCOS patients: a systematic review and meta-analysis.

BACKGROUND: This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS). METHODS: A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239). RESULTS: A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p < 0.01). No statistically significant difference was observed in nitroglycerin-mediated dilation (NMD) between the two groups (MD = 0.65, p = 0.51). Subgroup analysis showed that a relatively lower MD of CIMT in PCOS patients from Europe in the endpoint group compared with the baseline group (MD = -0.09, 95% CI = -0.14 to -0.04, p < 0.001). However, the MD in CIMT was not significantly different between the endpoint group and baseline group in PCOS patients from Asia (p = 0.270). CONCLUSION: Metformin may have a beneficial effect on CIMT and FMD, but not on NMD, suggesting that metformin may help reduce cardiovascular events in PCOS patients. Notably, the clinical efficacy of metformin can be influenced by regional differences and study types.

The Essential Oils Obtained from (Lonicerae japonicae Flos) Flower Buds Could Affect the Deposition of Sunflower Oil under Common High Temperature Conditions and the Traditional Frying Process in Maye.

The essential oil extracted from the flower buds of Lonicerae japonicae (LJEO) was employed in the high-temperature (65℃) accelerated preservation of sunflower oil. In the present investigation, the addition of the essential oil at a concentration of 800 ppm significantly inhibited the decrease in the oxidative stability of sunflower oil. This positive effect was achieved by significantly hindering the reduction in acidity value (AV), peroxide value (PV), p-anisidine value (AnV), the total oxidation value (TOTOX) (p < 0.01), and the levels of thiobarbituric acid reactive substance (TBARS), the absorbance at 232/268 nm (K232/K268) and total polar compounds (TPC) (p < 0.01). Besides, it also significantly enhances the sensory attributes of Maye, including taste, flavor, and appearance, improving its overall acceptability through the addition of certain potential fragrance molecules (p < 0.01). Furthermore, one of the primary chemical compounds in LJEO, eugenol, has demonstrated significant natural antioxidant properties in the traditional deep-frying procedure for the product, Maye. Consequently, together with eugenol, the essential oil LJEO could be employed as a possible effective antioxidant for the typical long-term preservation and even the traditional deep-frying procedures, and developed as effective antioxidant extracted from plants for the whole food industry.

Chinese Visceral Adiposity Index Predict Prehypertension Progression and Regression: A Prospective Cohort Study Involving Middle-Aged and Older Adults.

BACKGROUND: Limited data are published on the relationship of the Chinese visceral adiposity index (CVAI) with prehypertension progression or regression. Therefore, we investigated this association through the China Health and Retirement Longitudinal Study. METHODS: Participants with prehypertension were assigned to two groups according to baseline CVAI, and after 4 years of follow-up, their blood pressure was analyzed for deterioration or improvement. We constructed logistic regression models for assessing the association of CVAI with the progression or regression of prehypertension. A restricted cubic spline (RCS) model was utilized for determining the dose-response association. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: The study included 2,057 participants with prehypertension. During the follow-up, 695 participants progressed to hypertension, 561 participants regressed to normotension, and 801 participants remained as prehypertensive. An association was observed between a high CVAI value and a higher incidence of progression to hypertension and between a high CVAI value and a lower incidence of regression to normotension (OR = 1.66 and 0.58, 95% CI: 1.35-2.05 and 0.47-0.73, respectively). The RCS model exhibited a linear association between CVAI and prehypertension progression and regression (all P for non-linear > 0.05). The results of the subgroup and sensitivity analyses agreed with those of the primary analysis. CONCLUSIONS: A significant association was noted between CVAI and prehypertension progression and regression. Thus, as part of the hypertension prevention strategy, monitoring CVAI is crucial in individuals with prehypertension.

Multifunctional metalens optical tweezers for optical information recognition.

Traditional optical information recognition (OIR), particle capture and manipulation require many optical devices or mechanical moving system components to achieve a specific function, which is difficult to achieve integration. This paper proposes a new method to realize these functions by using multi-focus metalens combining spectrum and polarization selection. The design incorporates three spectral bands, namely 500 nm, 580 nm, and 660 nm, within the visible light range. Additionally, it utilizes either left-handed or right-handed circularly polarized (LCP/RCP) light, resulting in six distinct focus focusing effects on a single focal plane. By analyzing the normalized light intensity (NLI) at the corresponding focus position, the OIR of any wavelength and polarization detection in the design can be realized, and the particle capture at different focusing positions can be realized. Our work can provide a new idea for the high integration of on-chip light recognition and operation and inspire the design of a highly integrated optical system with a smaller size and more substantial function.

Primer extension refractory PCR: an efficient and reliable genome walking method.

Genome walking, a molecular technique for obtaining unknown flanking genomic sequences from a known genomic sequence, has been broadly applied to determine transgenic sites, mine new genetic resources, and fill in chromosomal gaps. This technique has advanced genomics, genetics, and related disciplines. Here, an efficient and reliable genome walking technique, called primer extension refractory PCR (PER-PCR), is presented. PER-PCR uses a set of primary, secondary, and tertiary walking primers. The middle 15 nt of the primary walking primer overlaps with the 3' parts of the secondary and tertiary primers. The 5' parts of the three primers are heterologous to each other. The short overlap allows the walking primer to anneal to its predecessor only in a relaxed-stringency PCR cycle, resulting in a series of single-stranded DNAs; however, the heterologous 5' part prevents the creation of a perfect binding site for the walking primer. In the next stringent cycle, the target single strand can be extended into a double-stranded DNA molecule by the sequence-specific primer and thus can be exponentially amplified by the remaining stringent cycles. The nontarget single strand fails to be enriched due to the lack of a perfect binding site for any primer. PER-PCR was validated by extension into unknown flanking regions of the hyg gene in rice and the gadR gene in Levilactobacillus brevis CD0817. In summary, in this study, a new practical PER-PCR method was constructed as a potential alternative to existing genome walking methods.

Effects of sigmoidoscopy screening (including colonoscopy) on colorectal cancer: A meta-analysis based on randomized controlled trials.

Background: This study aimed to investigate the role of endoscopy screening in colorectal cancer (CRC). Methods: Up to January 2023, databases were searched for studies related to sigmoidoscopy and colonoscopy screening. The incidence of CRC, and/or CRC mortality were the main observation outcomes. Results: A total of 5 randomized controlled trials (RCTs) published from 2017 to 2022 were included. Among them, four studies used sigmoidoscopy screening and one study involved colonoscopy screening. Statistical results showed that the incidence (RR: 0.78, p < 0.001) and mortality (RR: 0.75, p < 0.001) of CRC were significantly lower in the screening group than in the control group. Further, a subgroup analysis of CRC site indicated that the incidence and mortality of CRC in the screening group were significantly lower than those in the non-screened group, regardless of distal CRC (Incidence: RR: 0.66, p < 0.001; Mortality: RR: 0.62, p < 0.001) or proximal CRC (Incidence: RR: 0.94, p = 0.038; Mortality: RR: 0.89, p = 0.038). In terms of gender, compared with the non-screening group, both males (Incidence: RR: 0.73, p < 0.001; Mortality: RR: 0.68, p < 0.001) and females (Incidence: RR: 0.85, p < 0.001; Mortality: RR: 0.85, p = 0.017), the screening group had a significant decrease in the incidence and mortality of CRC. Conclusion: This meta-analysis demonstrated that sigmoidoscopy screening (including colonoscopy) could effectively reduce the incidence and mortality of CRC.

Seroprevalence of Toxoplasma gondii in water buffaloes and cats in Guangxi, China.

Toxoplasma gondii is a pathogen that poses a serious threat to human health and causes significant economic losses to the global livestock industry. The prevalence of toxoplasmosis infection has been reported to be high in humans and animals around the world, but the occurrence of the disease has not yet been reported in water buffaloes in Guangxi Zhuang Autonomous Region, southern China. To understand the overall seroprevalence of T. gondii infection in Guangxi, a total of 1041 water buffalo and 114 cat serum samples were examined using an indirect enzyme-linked immunosorbent assay (I-ELISA). Of the 1041 water buffaloes analyzed, an overall seroprevalence of 52.9% (551/1041) was obtained, with year, season, and city location being significant factors affecting the rate of T. gondii infection in water buffaloes (P < 0.001). The results also revealed a high seroprevalence of 57% (65/114) in cats. Given that buffalo milk and meat products are vital food sources, these findings suggest that toxoplasmosis in water buffaloes may be a public health threat. This study provides the first T. gondii seroprevalence data in Guangxi, which could contribute to the prevention and control of toxoplasmosis in the region.

Chlamydia psittaci Pneumonia in a patient with motor neuron disease: a case report.

BACKGROUND: Motor neuron disease (MND) is a fatal neurodegenerative disorder that leads to progressive loss of motor neurons. Chlamydia psittaci (C. psittaci) is a rare etiology of community-acquired pneumonia characterized primarily by respiratory distress. We reported a case of C. psittaci pneumonia complicated with motor neuron disease (MND). CASE PRESENTATION: A 74-year-old male was referred to the Shaoxing Second Hospital at January, 2022 complaining of fever and fatigue for 2 days. The patient was diagnosed of MND with flail arm syndrome 1 year ago. The metagenomic next-generation sequencing (mNGS) of sputum obtained through bedside fiberoptic bronchoscopy showed C. psittaci infection. Then doxycycline was administrated and bedside fiberoptic bronchoscopy was performed to assist with sputum excretion. Computed Tomography (CT) and fiberoptic bronchoscopy revealed a significant decrease in sputum production. On day 24 after admission, the patient was discharged with slight dyspnea, limited exercise tolerance. One month later after discharge, the patient reported normal respiratory function, and chest CT showed significant absorption of sputum. CONCLUSIONS: The mNGS combined with bedside fiberoptic bronchoscopy could timely detect C. psittaci infection. Bedside fiberoptic bronchoscopy along with antibiotic therapy may be effective for C. psittaci treatment.

Influence of the Essential Oil of Foeniculum vulgare Mill. on Sunflower Oil during the Deep-frying Process of Chinese Maye.

Sunflower oil (SFO) is faced with serious oxidation problems during the deep-frying of Chinese Maye, and the search for natural antioxidants has become a focus of scientific research due to the potential toxicity of synthetic antioxidants. In the present study, the Foeniculum vulgare Mill. essential oil (FVEO), tert-butylhydroquinone (TBHQ) were added to SFO for a 30 h deep frying experiment and the results showed that FVEO added to sunflower oil at 1 g/kg was similar to that of TBHQ-0.01 g/kg, and FVEO-1.5 g/kg would promote the oxidation of SFO. FVEO to sunflower oil also prominently restrained the decrease of the sensory properties of the fried product, Chinese Maye, including appearance, taste, flavor and overall acceptance by 24.2%, 20.2%, 46.1% and 56.0% (p < 0.01 or p < 0.05), respectively. The results indicated that FVEO could be used as a natural antioxidant to replace TBHQ in the deep-frying process of SFO, but further research is needed on the key antioxidant constituent of FVEO.

The efficacy and safety of anti-EGFR target agents in patients with potentially resectable metastatic colorectal cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Adding anti-epidermal growth factor receptor (anti-EGFR) target agents to conversion therapy may improve the resection rates and survival of patients with potentially resectable metastatic colorectal cancer (mCRC). This study aims to analyze the efficacy and safety of additional anti-EGFR target agents. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library. And all relevant studies published in English before January 2023 were collected to explore the impact of additional anti-EGFR targeted agent on the efficacy and safety of patients with potentially resectable mCRC (PROSPERO: CRD42022340523, https://www.crd.york.ac.uk/PROSPERO/ ). RESULTS: This study included a total of 8 articles, including 2618 patients. The overall response rate (ORR) and R0 resection rates of the experimental group were higher than those of the control group, while there was no significant difference in progression-free survival (PFS) and overall survival (OS) between the two groups. In RAS/KRAS wild-type patients, the ORR (RR: 1.20, 95% Cl: 1.02-1.41, p = 0.03), R0 resection rate (RR: 1.60, 95% Cl: 1.17-2.20, p = 0.003), PFS (HR: 0.80, 95% Cl: 0.68-0.93, p = 0.003), and OS (HR: 0.87, 95% Cl: 0.76-0.99, p = 0.031) of the experimental group were higher than those of the control group. While in KRAS mutant patients, there was no statistical difference between the two groups in ORR, R0 resection rate, PFS, and OS. CONCLUSION: The addition of anti-EGFR targeted agents can improve the prognosis of RAS/KRAS wild-type patients with potentially resectable mCRC, while KRAS mutant patients may not benefit. In addition, the overall safety factor was controllable.

Association between statins exposure and risk of skin cancer: an updated meta-analysis.

This study aimed to investigate the relationship between statin (lipophilic statin and hydrophilic statin) exposure and the risk of skin cancer. The incidence of skin cancer under statin exposure was used as the primary outcome, and the relevant studies were screened from Web of Science, PubMed, Cochrane Library, and EBSCO electronic database until September 2022. Ten observational studies and two randomized controlled trials (RCTs) were included. The statistical results indicated that in lipophilic statins, the exposed group had a higher risk of skin cancer than the non-exposed group (OR: 1.09, P = 0.003). However, compared with the non-exposed group, there was no significant difference between hydrophilic statins exposure and the incidence of skin cancer (OR: 1.02, P = 0.341). Further subgroup analysis of the subtypes of statins revealed that compared with the non-exposed group, exposure to lovastatin (OR: 1.18, P = 0.048) or simvastatin (OR: 1.11, P < 0.001) was a risk factor for skin cancer. Besides, subgroup analysis based on the subtypes of skin cancer demonstrated that the risks of melanoma (OR: 1.13, P = 0.009), basal cell carcinoma (BCC) (OR: 1.05, P = 0.036), and squamous cell carcinoma (SCC) (OR: 1.13, P = 0.026) under lipophilic statin exposure were significantly higher than those in the non-exposed group. On the contrary, compared with the non-exposed group, the risk of BCC was significantly reduced under the exposure of hydrophilic statins (OR: 0.93, P = 0.031). This study showed that the relationship between statin exposure and skin cancer risk was affected by the subtypes of statins and skin cancer subtypes.

Bidirectional association between handgrip strength and ADLs disability: a prospective cohort study.

Background: Decreased handgrip strength (HGS) and activities of daily living (ADL) disability are common in aging populations. No studies have evaluated the bidirectional associations between HGS and ADL disability. This study aimed to explore the bidirectional effects of HGS and ADL disability. Methods: This study analyzed data from two waves (2011 and 2015) of China Health and Retirement Longitudinal Study (CHARLS). Low HGS is defined by the Asian Working Group for Sarcopenia criteria. Meanwhile, disability was assessed by ADLs scale. The prospective bidirectional association between HGS and ADL disability was examined using binary logistic regression. Subgroup analysis were performed according to age and gender. Results: A total of 4,902 and 5,243 participants were included in the Stage I and Stage II analyses, respectively. On the one hand, low HGS was significantly associated with subsequent ADL disability. The odds ratio (OR) value of developing BADL disability and IADL disability were 1.60 (95% confidence interval (CI): 1.23-2.08) and 1.40 (95% CI: 1.15-1.70), respectively, in participants with low HGS. On the other hand, baseline ADL disability was associated with an increased risk of developing low HGS. The OR value of developing low HGS were 1.84 (95% CI: 1.34-2.51) and 1.46 (95% CI: 1.19-1.79) for participants with BADL disability and participants with IADL disability, respectively. Lastly, the strength of the bidirectional associations varied among subgroups. Conclusions: A significant bidirectional associations were identified between HGS and ADL disability. Interventions should be developed to prevent the development or progression of both low HGS and ADL disability.

FAT4 overexpression promotes antitumor immunity by regulating the ß-catenin/STT3/PD-L1 axis in cervical cancer.

BACKGROUND: FAT4 (FAT Atypical Cadherin 4) is a member of the cadherin-associated protein family, which has been shown to function as a tumor suppressor by inhibiting proliferation and metastasis. The Wnt/ß-catenin pathway activation is highly associated with PD-L1-associated tumor immune escape. Here, we report the mechanism by which FAT4 overexpression regulates anti-tumor immunity in cervical cancer by inhibiting PD-L1 N-glycosylation and cell membrane localization in a ß-catenin-dependent manner. METHODS: FAT4 expression was first detected in cervical cancer tissues and cell lines. Cell proliferation, clone formation, and immunofluorescence were used to determine the tumor suppressive impact of FAT4 overexpression in vitro, and the findings were confirmed in immunodeficient and immunocomplete mice xenografts. Through functional and mechanistic experiments in vivo and in vitro, we investigated how FAT4 overexpression affects the antitumor immunity via the ß-catenin/STT3/PD-L1 axis. RESULTS: FAT4 is downregulated in cervical cancer tissues and cell lines. We determined that FAT4 binds to ß-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of ß-catenin by the degradation complexes (AXIN1, APC, GSK3ß, CK1). FAT4 overexpression decreases programmed death-ligand 1 (PD-L1) mRNA expression at the transcriptional level, and causes aberrant glycosylation of PD-L1 via STT3A at the post-translational modifications (PTMs) level, leading to its endoplasmic reticulum (ER) accumulation and polyubiquitination-dependent degradation. We found that FAT4 overexpression promotes aberrant PD-L1 glycosylation and degradation in a ß-catenin-dependent manner, thereby increasing cytotoxic T lymphocyte (CTL) activity in immunoreactive mouse models. CONCLUSIONS: These findings address the basis of Wnt/ß-catenin pathway activation in cervical cancer and provide combination immunotherapy options for targeting the FAT4/ß-catenin/STT3/PD-L1 axis. Schematic cartoons showing the antitumor immunity mechanism of FAT4. (left) when Wnts bind to their receptors, which are made up of Frizzled proteins and LRP5/6, the cytoplasmic protein DVL is activated, inducing the aggregation of degradation complexes (AXIN, GSK3ß, CK1, APC) to the receptor. Subsequently, stable ß-catenin translocates into the nucleus and binds to TCF/LEF and TCF7L2 transcription factors, leading to target genes transcription. The catalytically active subunit of oligosaccharyltransferase, STT3A, enhances PD-L1 glycosylation, and N-glycosylated PD-L1 translocates to the cell membrane via the ER-to-Golgi pathway, resulting in immune evasion. (Right) FAT4 exerts antitumor immunity mainly through following mechanisms: (i) FAT4 binds to ß-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of ß-catenin by the degradation complexes (AXIN1, APC, GSK3ß, CK1); (ii) FAT4 inhibits PD-L1 and STT3A transcription in a ß-catenin-dependent manner and induces aberrant PD-L1 glycosylation and ubiquitination-dependent degradation; (iii) Promotes activation of cytotoxic T lymphocytes (CTL) and infiltration into the tumor microenvironment.

Design of OMC-Sagnac Loop Using PDMS and Different Package Structures to Improve Sensing Performance and Optimize the Ill-Conditioned Matrix.

In the process of ocean exploration, highly accurate and sensitive measurements of seawater temperature and pressure significantly impact the study of seawater's physical, chemical, and biological processes. In this paper, three different package structures, V-shape, square-shape, and semicircle-shape, are designed and fabricated, and an optical microfiber coupler combined Sagnac loop (OMCSL) is encapsulated in these structures with polydimethylsiloxane (PDMS). Then, the temperature and pressure response characteristics of the OMCSL, under different package structures, are analyzed by simulation and experiment. The experimental results show that structural change hardly affects temperature sensitivity, and square-shape has the highest pressure sensitivity. In addition, with an input error of 1% F.S., temperature and pressure errors were calculated, which shows that a semicircle-shape structure can increase the angle between lines in the sensitivity matrix method (SMM), and reduce the effect of the input error, thus optimizing the ill-conditioned matrix. Finally, this paper shows that using the machine learning method (MLM) effectively improves demodulation accuracy. In conclusion, this paper proposes to optimize the ill-conditioned matrix problem in SMM demodulation by improving sensitivity with structural optimization, which essentially explains the cause of the large errors for multiparameter cross-sensitivity. In addition, this paper proposes to use the MLM to solve the problem of large errors in the SMM, which provides a new method to solve the problem of the ill-conditioned matrix in SMM demodulation. These have practical implications for engineering an all-optical sensor that can be used for detection in the ocean environment.