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Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.

Background and aims: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. Methods: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. Results: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099–0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129–0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. Conclusion: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

Abstract Background Gastroesophageal reflux disease (GERD) is among the most common complications of bariatric surgery. This study aimed to analyse the risk factors affecting the worsening of GERD symptoms after laparoscopic sleeve gastrectomy (LSG), and to establish and validate a related nomogram model. Methods The study recruited 236 participants and randomly divided them into training and validation sets in a ratio of 7:3. LASSO regression technique was used to select the optimal predictive features, and multivariate logistic regression was used to construct the column line graphs. The performance of the nomogram was evaluated and validated by analyzing the area under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results In this study, Lasso-logistic regression was applied to select 5 predictors from the relevant variables, which were body mass index (BMI), diabetes, hiatal hernia, GERD, and triglyceride levels. These 5 predictor variables constructed a model with moderate predictive power, with an area under the ROC curve of 0.779 for the training set and 0.796 for the validation set. Decision curve analysis showed that in external validation, if the risk thresholds were between 4 and 98% and 14–95%, then the nomogram can be applied to the clinic. Conclusions We have developed and validated a nomogram that effectively predicts the risk of worsening gastroesophageal reflux symptoms following LSG.

Abstract Background & aims The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. Methods Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). Results Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378–0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379–0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. Conclusion Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.

Abstract Background Epstein-Barr virus (EBV) infection has been closely linked to the development of various types of cancer. EB nuclear antigen 1 binding protein 2 (EBNA1BP2) is a crucial molecule for stable isolation of EBV in latent infection. However, the role of EBNA1BP2 in multiple tumor types is remains unclear. In this study, we comprehensively analyzed the functional characteristics of EBNA1BP2 and investigate its potential as a prognostic biomarker in pan-cancer. Methods We utilized data from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) databases and employed various bioinformatics analysis tools, including TIMER2.0, HPA, GEPIA2.0, PrognoScan, cBioPortal, CancerSEA, and BioGRID to explore the expression pattern, prognostic value, immune infiltration, and methylation level of EBNA1BP2 in pan-cancer. Additionally, we conducted enrichment analysis of genes associated with EBNA1BP2 to identify potential biological functions and pathways. Results Our analysis revealed that EBNA1BP2 expression was significantly higher in tumor tissues compared to tumor-adjacent tissues. We observed that lower expression of EBNA1BP2 in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), sarcoma (SARC), and uterine carcinosarcoma (UCS) was significantly associated with improved overall survival (OS) and disease-free survival (DFS). Furthermore, the promoter methylation level of EBNA1BP2 was downregulated in the majority of cancer types. At the single-cell level, EBNA1BP2 was found to be positively correlated with cell cycle and DNA repair processes, while negatively correlated with hypoxia. Additionally, EBNA1BP2 was associated with the infiltration of immune cells such as B cells, cancer-associated fibroblast cells, and CD8+ T cells. Gene enrichment analysis indicated that EBNA1BP2 was mainly involved in nucleoplasm and RNA binding pathways. Conclusion Our findings suggest that EBNA1BP2 may serve as a potential prognostic biomarker for survival in pan-cancer. Further experimental studies are needed to validate these findings and explore the underlying mechanisms by which EBNA1BP2 contributes to tumorigenesis.

To optimize the processing technology of Gastrodia elata by water in which millet had been cooked and investigate the effects of LPS-induced microglia (BV2) inflammatory responses. Determination of gastrodin, p-hydroxybenzyl alcohol, parishin A, parishin B, parishin C, parishin E in the extract of Gastrodia elata by high-performance liquid chromatography (HPLC), and the content of six components were used as evaluation index, the volume ratio of water in which millet had been cooked to water, cooking time and drying temperature were selected as single factor variables. The designation of orthogonal test was based on single factor on three indicators, then optimization of the preparation technology. Comparison of the content of six components in different processed product. The neuroinflammatory cell model was induced by LPS and the cell viability was evaluated after treatment with the extract of processed products by a Cell Counting kit 8 (CCK-8) assay. The levels of TNF-α, IL-6, IL-1β in the cell culture medium were measured with ELISA kits. The protein expressions of TLR4, MYD88, P65, INOS, COX-2, IL-1β in LPS-induced BV2 cells were detected by Western blot. The results showed that the cooking time and the volume ratio of water in which millet had been cooked to water had a significant effect on the test results. The water in which millet had been cooked of Gastrodia elata processing technology: The ratio of the volume water in which millet had been cooked to water was 1:3, the boiling time was 25 min and the temperature of drying was 75 ℃. The comprehensive score of the six components in processing with water in which millet had been cooked products was higher than that of steamed products. The extract of Gastrodia elata had exhibited varying degrees of protective activity on LPS-induced BV2 cells. The results showed that the secretion of TNF-α, IL-6, IL-1β was significantly increased in BV2 microglial cells induced by LPS compared with the normal control group (P

Abstract Fractional flow reserve (FFR) has become the gold standard for evaluating coronary lesion-specific ischemia. However, FFR is an invasive method that may cause possible complications in the coronary artery and requires expensive equipment, which limits its use. Promising noninvasive diagnostic methods, such as computed tomography angiography–derived FFR (CT-FFR) and the quantitative flow ratio (QFR), have been proposed. In this study, we evaluated the diagnostic performance of the QFR and CT-FFR in predicting coronary lesion-specific ischemia, with the FFR serving as the reference standard. Patients with suspected or known coronary artery disease who underwent coronary CT angiography revealing 30–90% diameter stenosis in the main coronary artery (≥ 2.0 mm reference diameter) were enrolled. The FFR was measured during invasive coronary angiography (within 15 days after coronary CT angiography). An FFR ≤ 0.8 was the reference standard for coronary lesion-specific ischemia. A total of 103 vessels from 92 consecutive patients (aged 59.8 ± 9.2 years; 60.9% were men) were evaluated. The diagnostic performance of a QFR ≤ 0.80 for predicting coronary lesion-specific ischemia demonstrated good diagnostic accuracy, sensitivity, and specificity (92.2%, 87.2%, and 96.4%, respectively), with an area under the receiver operating characteristic curve (AUC) of 0.987 (P

Introduction: Mechanical ventilation after respiratory insufficiency can induce diaphragm dysfunction through various hypothesized mechanisms. In this study, we evaluated the rehabilitative effect of acupuncture on diaphragm function in patients with respiratory insufficiency using meta-analysis and summarised the rules of acupoints through association rules analysis. Methods: Articles (published from January 2000 to February 2024) were retrieved from the following databases: PubMed, Cochrane Library, Embase, Web of Science, CNKI, VIP, SinoMed, and Wanfang. Two researchers conducted literature selection, data extraction, and statistical analysis independently. The risk of bias was assessed utilizing the Physical Therapy Evidence Database (PEDro) scale. The meta-analysis was performed with RevMan 5.4 software, and the quality of each outcome evidence was assessed via the online software GRADEpro GDT. The regularity of acupoint selection was summarized using association rules analysis. This study is registered on PROSPERO, number CRD42024526705. Results: Eleven articles were eventually included, all of which were of low to moderate quality. Results of the meta-analysis showed a significant increase in diaphragmatic thickening fraction (MD 3.40 [1.52, 5.27]) and diaphragmatic excursion (MD 0.95 [0.58, 1.31]) in patients with respiratory insufficiency after acupuncture treatment. Also, OI (MD 28.52 [15.93, 41.11]) and PaO2 (MD 7.18 [2.22, 12.13]) were significantly elevated and PaCO2 (MD −6.94 [-12.30, −1.59]) was decreased. Mechanical ventilation time (MD-1.86 [-2.28, −1.45]) was also significantly improved. The overall quality of the outcome evidence is deemed moderate. Association rules analysis showed that ST36, RN4, RN6, and others are core acupoints for the treatment of diaphragmatic dysfunction in patients with respiratory insufficiency by acupuncture. Conclusion: Acupuncture shows potential in the rehabilitation of patients with respiratory insufficiency and may serve as a complementary and alternative therapy for related conditions. We suggest the use of ST36 as a core acupoint, in combination with other acupoints. Due to the potential publication bias and high heterogeneity of the current data, further high-quality RCTs are needed to confirm these findings.

Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous chemicals routinely detected in personal care products (PCPs). However, few studies have evaluated the impact of PCP use on PFAS concentrations in pregnant and lactating populations. Objective: We investigated associations between PCP use and PFAS concentrations in prenatal plasma and human milk. Methods: We leveraged the Maternal-Infant Research on Environmental Chemicals (MIREC) Study to evaluate the contribution of PCP use on PFAS concentrations in prenatal plasma (6 to 13 weeks’ gestation; n = 1,940) and human-milk (2 to 10 weeks’ postpartum; n = 664). Participants reported frequency of use across 8 PCP categories during the 1st and 3rd trimesters, 1 to 2 days postpartum, and 2 to 10 weeks’ postpartum. We used adjusted linear regression models to quantify percent differences and corresponding 95 % confidence intervals. Results: In 1st trimester pregnant people, we found higher use of nailcare products (≥once a week vs. never: perfluorooctanoic acid (PFOA): 21 % [9.7 %, 32 %]; perfluorooctane-sulfonic acid (PFOS): 11 % [0.3 %, 23 %]), fragrances (daily vs. never: PFOA: 14 % [7.8 %, 21 %]; PFOS: 7.8 % [1.3 %, 15 %]), makeup (daily vs. never: PFOA: 14 % [5.8 %, 23 %]), hair dyes (never vs. 1-2 times during pregnancy: PFOA: 8.3 % [2.4 %, 15 %]), and hair sprays or gels (daily vs. never: PFOA: 12 % [5.0 %, 19 %], PFOS: 7.1 % [0.2 %, 15 %]) were associated with higher plasma PFAS concentrations. Similar results were observed for 3rd trimester PCP use and 2 to 10 weeks’ postpartum human-milk PFAS concentrations. In addition, we also found that people using colored-permanent dye 1 to 2 days postpartum had higher Sm-PFOS (18 % [2.7 %, 35 %]), PFOA (16 % [4.3 %, 29 %]), and perfluorononanoic acid (17 % [3.6 %, 33 %]) postpartum human-milk concentrations. Conclusions: Our results show that PCP use may be a modifiable source of PFAS exposure in pregnant and lactating populations. These results along with growing scientific evidence can help inform PFAS regulation and guide individual choices to reduce PFAS exposure.

Narrow-linewidth semiconductor lasers are highly valued in scientific research and industrial applications owing to their high coherence and low phase noise characteristics, particularly in high-performance optical communications, sensing, and microwave photonic systems. Accuracy, a key objective of many application systems, is determined by the noise of the light source. As system accuracy improves, the requirements for the light source become more stringent, with linewidth reduction and noise reduction being the top priorities. Currently, extensive attention and research are focused on suppressing noise generated by narrow-linewidth lasers. This paper presents noise measurement methods, analyses of the mechanisms for noise suppression, and recent research progress in low-noise semiconductor lasers, focusing on material optimization, structural design, and feedback control. The limitations of current technological solutions are discussed, and future scientific trends are outlined.

Abstract Although robotic radical resection for hilar cholangiocarcinoma (HCCA) has been reported in some large hepatobiliary centers, biliary-enteric reconstruction (BER) remains a critical step that hampers the operation’s success. This study aimed to evaluate the feasibility and quality of BER in robotic radical resection of HCCA and propose technical recommendations. A retrospective study was conducted on patients with HCCA who underwent minimally invasive radical resection at Zhejiang Provincial People’s Hospital between January 2016 and July 2023. A 1:2 propensity score matching (PSM), widely used to reduce selection bias, was performed to evaluate the outcomes, especially BER-related data, between the robotic and laparoscopic surgery. Forty-six patients with HCCA were enrolled; ten underwent robotic-assisted resection, while the others underwent laparoscopic surgery. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robot-assisted and laparoscopic groups, respectively. The baseline characteristics of both groups were generally well-balanced. The average liver resection time was longer in the robotic group than in the laparoscopic group (139.5 ± 38.8 vs 108.1 ± 35.8 min, P = 0.036). However, the former had less intraoperative blood loss [200 (50–500) vs 310 (100–850) ml], despite no statistical difference (P = 0.109). The number of residual bile ducts was 2.6 ± 1.3 and 2.7 ± 1.2 (P = 0.795), and anastomoses were both 1.6 ± 0.7 in the two groups (P = 0.965). The time of BER was 38.4 ± 13.6 and 59.1 ± 25.5 min (P = 0.024), accounting for 9.9 ± 2.8% and 15.4 ± 4.8% of the total operation time (P = 0.001). Although postoperative bile leakage incidence in laparoscopic group (40%) was higher than that in robotic group (10%), there was no significant difference between the two groups (P = 0.204); 6.7 ± 4.4 and 12.1 ± 11.7 days were observed for tube drawing (P = 0.019); anastomosis stenosis and calculus rate was 10% and 30% (P = 0.372), 0% and 15% (P = 0.532), respectively. Neither group had hemorrhage- or bile leakage-related deaths. Robotic radical resection for HCCA may offer perioperative outcomes comparable to conventional laparoscopic procedures and tends to be advantageous in terms of anastomosis time and quality. We are optimistic about its wide application in the future with the improvement of surgical techniques and experience.

Abstract Background The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. Methods Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. Results A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022–3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259–4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184–3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519–4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. Conclusions NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Abstract Background & aims Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. Methods Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. Results Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P

Objective: The cause of syncope is generally determined based on clinical manifestations. There has been little discussion about the value of electrocardiograms for diagnosing neurally mediated syncope. The aim of this study was to test the predictive value of the isolated very low QRS voltage in tilt-table testing for suspected neurally mediated syncope in a Chinese population. Methods: This retrospective study enrolled patients with suspected neurally mediated syncope. Tilt-table testing was a part of the diagnostic examination. Each patient underwent echocardiography and electrocardiogram. isolated very low QRS voltage referred to a voltage of ⩽0.3 mV for the QRS complex in an isolated frontal lead or ⩽0.7 mV for the QRS complex in an isolated precordial lead. Results: In total, 157 patients were included in the tilt-table testing positive group, and 242 patients were included in the tilt-table testing negative group. Compared with the testing negative group, the testing positive group had more patients with isolated very low QRS voltage in the frontal leads ( p

Ionic conductive hydrogel has recently garnered significant research attention due to its potential applications in the field of wearable and flexible electronics. Nonetheless, the integration of multifunctional and synergistic advantages, including reliable electronic properties, high swelling capacity, exceptional mechanical characteristics, and self-adhesive properties, presents an ongoing challenge. In this study, we have developed an ionic conductive hydrogel through the co-polymerization of 4-Acryloylmorpholine (ACMO) and sodium acrylate using UV curing technology. The hydrogel exhibits excellent mechanical properties, high conductivity, superior swelling capacity, and remarkable self-adhesive attributes. The hydrogel serves as a highly sensitive strain sensor, enabling precise monitoring of both substantial and subtle human motions. Furthermore, the hydrogel demonstrates the capability to adhere to human skin, functioning as a human-machine interface for the detection of physiological signals, including electromyogram (EMG) signals, with low interfacial impedance. This work is anticipated to yield a new class of stretchable and conductive materials with diverse potential applications, ranging from flexible sensors and wearable bio-electronics to contributions in the field of artificial intelligence.

Abstract Background Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. Methods The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (

Abstract Background This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). Methods Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. Results Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (β= − 0.060, 95% CI − 0.044 to − 0.076; P = 2.416e−14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (β= − 0.021, 95% CI − 0.003 to − 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. Conclusions Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice.

The BeiDou Navigation Satellite System (BDS-3) has officially provided services worldwide since July 2020. BDS-3 has added new signals for B1C, B2a and B2b based on old BDS-2 B1I and B3I signals, which brings opportunities for achieving high-precision time transfer. In this research, the BDS-3/BDS-2 combined penta-frequency common-view (CV) single-differenced (SD) precise time transfer model is established with B1I, B3I, B2I, B1C, B2a and B2b signals, including dual-, triple-, quad- and penta-frequency (abbreviated as DF, TF, QF and PF) ionosphere-free (IF) combination CV SD models. Taking four long baseline time links (from 637.6 km to 1331.6 km) as examples, the accuracy and frequency stability of the BDS-3/BDS-2 combined DF, TF, QF and PF SD time transfer models were evaluated. The experimental results show that the frequency stability of the TF, QF and PF SD models were improved by 2.5%, 5.3% and 8.5%, on average, over the DF SD model. Compared with the traditional DF (B1I/B3I IF combination) SD model, the standard deviation (STD) of the multi-frequency SD model was reduced by 5.9%, on average, and the frequency stability was improved by 4.0% on average, which had the most apparent effect on the improvement of short-term frequency stability. Specifically, the DF1 (B1C and B2a DF IF combination), TF1 (B1C, B2a and B2b TF IF combination), QF1 (B1C, B1I, B2a and B2b QF IF combination) and PF4 (B1C, B1I, B2a, B2b and B3I PF IF combination) SD models had better performance in timing, and the PF4 SD model had the best performance. Considering that the PF4 (one PF signal IF combination) SD model does not require an estimated inter-frequency bias and that its noise factor is minor compared with the PF1 (four DF signal IF combination), PF2 (three TF signal IF combination) and PF3 (two QF signal IF combination) SD models, we recommend the PF4 SD model for multi-frequency time transfer and the use of the PF2, PF2 or PF3 SD model to supplement the PF4 SD model in cases of penta-frequency observation loss.

Alport Syndrome (AS) is a genetic kidney disorder characterized by progressive hearing loss and atypical eye symptoms, resulting in a poor prognosis and lack of effective targeted therapy. The primary mode of inheritance is X-linked dominant (XLAS) due to variants in the COL4A5 gene. This study revealed a previously unidentified alternative form of the COL4A5 gene, namely, the c.4822–10T>C variant, which was confirmed through in vitro experiments. To investigate the impact of a splicing variant on COL4A5 mRNA production, an in vitro minigene splicing assay was utilized. Additionally, molecular dynamics was employed to predict the ability of α5(IV) to form a triple helix. Results from the experiment revealed that the wild-type (WT) plasmid produced two distinct mRNA products simultaneously. Sequence analysis using the BLAST database revealed a 173-bp deletion in the mRNA sequence of the first product, indicating a potential similarity to the XM_016942897.2 transcript of Pan troglodytes. The second mRNA product of the WT plasmid contained the full sequence of exons 51, 52, and 53, as anticipated. Conversely, the mutant (MT) plasmid generated a single mRNA product with a 173-bp deletion in exon 52, leading to the identification of the mature mRNA expression as NM_033380.2: COL4A5: c.4822_4994del. In the context of nonsense-mediated mRNA decay (NMD), the deletion c.4822_4994 results in the production of a truncated protein, p.His1608*, that terminates prematurely. This truncated protein may disrupt the secondary structure of α5(IV) and potentially cause an abnormal conformation of α345(IV). This study examines the relationship between the variable splicing pattern in the NM_033380.2 transcript of the COL4A5 gene in XLAS patients and the presence of the COL4A5 gene splice variant c.4822–10T>C. Our findings indicate that the c.4822–10T>C splice variant leads to activation of nonsense-mediated mRNA degradation (NMD) and reduced COL4A5 mRNA expression, resulting in inadequate synthesis of the corresponding proteins. This aligns with the patient’s immunofluorescence results showing negative α5(IV) chain presence at the glomerular basement membrane, bursa, and tubular basement membrane, confirming the pathogenic nature of c.4822–10T>C.

Abstract Background Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy. Methods Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR. Results 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P

Abstract With advances in tissue engineering and bioelectronics, flexible electronic hydrogels that allow conformal tissue integration, online precision diagnosis, and simultaneous tissue regeneration are expected to be the next-generation platform for the treatment of myocardial infarction. Here, we report a functionalized polyaniline-based chronological adhesive hydrogel patch (CAHP) that achieves spatiotemporally selective and conformal embedded integration with a moist and dynamic epicardium surface. Significantly, CAHP has high adhesion toughness, rapid self-healing ability, and enhanced electrochemical performance, facilitating sensitive sensing of cardiac mechanophysiology-mediated microdeformations and simultaneous improvement of myocardial fibrosis-induced electrophysiology. As a result, the flexible CAHP platform monitors diastolic-systolic amplitude and rhythm in the infarcted myocardium online while effectively inhibiting ventricular remodeling, promoting vascular regeneration, and improving electrophysiological function through electrocoupling therapy. Therefore, this diagnostic and therapeutic integration provides a promising monitorable treatment protocol for cardiac disease.

This paper introduces a semiconductor optical amplifier (SOA) with high power and narrow linewidth broadening achieved through active region mode control. By integrating mode control with broad-spectrum epitaxial material design, the device achieves high gain, high power, and wide band output. At a wavelength of 1550 nm and an ambient temperature of 20 °C, the output power reaches 757 mW when the input power is 25 mW, and the gain is 21.92 dB when the input power is 4 mW. The 3 dB gain bandwidth is 88 nm, and the linewidth expansion of the input laser after amplification through the SOA is only 1.031 times. The device strikes a balance between high gain and high power, offering a new amplifier option for long-range light detection and ranging (LiDAR).

As LiDAR technology progressively advances, the capability of radar in detecting targets has become increasingly vital across diverse domains, including industrial, military, and automotive sectors. Frequency-modulated continuous-wave (FMCW) LiDAR in particular has garnered substantial interest due to its efficient direct velocity measurement and excellent anti-interference characteristics. It is widely recognized for its significant potential within radar technology. This study begins by elucidating the operational mechanism of FMCW LiDAR and delves into its basic principles. It discuss, in depth, the influence of various parameters on FMCW LiDAR’s performance and reviews the latest progress in the field. This paper proposes that future studies should focus on the synergistic optimization of key parameters to promote the miniaturization, weight reduction, cost-effectiveness, and longevity of FMCW LiDAR systems. This approach aims at the comprehensive development of FMCW LiDAR, striving for significant improvements in system performance. By optimizing these key parameters, the goal is to promote FMCW LiDAR technology, ensuring more reliable and accurate applications in automated driving and environmental sensing.