The association of systemic inflammatory response index and neutrophil-to-high-density lipoprotein ratio mediated by fasting blood glucose with 90-day prognosis in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: The contribution of individual and combined inflammatory markers for the prognosis of acute ischemic stroke (AIS) remains elusive. This study investigated the effect of systemic inflammatory response index (SIRI), and neutrophil to high-density lipoprotein ratio (NHR), which is mediated by fasting blood glucose (FBG), on 90-day prognosis of patients with AIS. METHODS: In this pre-specified substudy of an observational cohort study, 2828 patients with AIS were enrolled from the Nanjing Stroke Registry between January 2017 to July 2021. Peripheral venous blood was collected from patients fasting for at least 8 hours within 24 hours of admission to gather information on the following parameters: neutrophil count, lymphocyte count, monocyte count, HDL level, and fasting blood glucose level. Then, the SIRI and NHR values were calculated. Following this, the correlation among SIRI, NHR, and modified Rankin Scale (mRS) scores 90d after onset was examined via univariate and multivariate logistic analyses. Lastly, mediation analysis was performed to examine the relationship between systematic inflammatory response and study outcomes mediated by FBG. RESULTS: SIRI and NHR were both negatively correlated with clinical outcomes (p < 0.05). Logistic regression analysis revealed that SIRI and NHR were independently associated with poor outcomes after adjusting for potential confounders. Subgroup analyses further validated these correlations. Meanwhile, mediation analysis corroborated that FBG partially mediated the associations between SIRI and a poor prognosis at 90d (indirect effect estimate = 0.0038, bootstrap 95% CI 0.001 to 0.008; direct effect estimate = 0.1719, bootstrap 95% CI 0.1258 to 0.2179). Besides, FBG also played a mediating role between NHR and poor outcomes (indirect effect estimate = 0.0066, bootstrap 95% CI 0.002 to 0.120; direct effect estimate = 0.1308, bootstrap 95% CI 0.0934 to 0.1681). CONCLUSIONS: Our study demonstrated that SIRI and NHR are positively associated with poor clinical and mortality outcomes at 90d in AIS patients, which was partially mediated by FBG.

Generation of FOXJ1-EGFP knock-in reporter human embryonic stem cell line, WAe001-A-2D, using CRISPR/Cas9-based gene targeting.

Forkhead box protein J1 (FOXJ1), a member of the forkhead family, is an important transcription factor regulating multiciliated cell differentiation and motile ciliogenic program. Here, we established a FOXJ1- EGFP knock-in human embryonic stem cell (hESC) line by inserting a P2A-EGFP gene cassette of FOXJ1 using CRISPR/Cas9 system. The reporter cell line retained a normal karyotype, expressed comparable pluripotent marker genes, and maintained differentiation potential. This reporter cell line enables live identification of multiciliated cells during the general lung differentiation and will be a valuable tool for studying the multiciliated cell differentiation, ciliogenesis and mechanism of related pulmonary diseases.

Nomogram to predict ventilator-associated pneumonia in large vessel occlusion stroke after endovascular treatment: a retrospective study.

Background: Ventilator-Associated Pneumonia (VAP) severely impacts stroke patients' prognosis after endovascular treatment. Hence, this study created a nomogram to predict the occurrence of VAP after endovascular treatment. Methods: The individuals with acute ischemic stroke and large vessel occlusion (AIS-LVO) who received mechanical ventilation and endovascular therapy between July 2020 and August 2023 were included in this retrospective study. The predictive model and nomogram were generated by performing feature selection optimization using the LASSO regression model and multifactor logistic regression analysis and assessed the evaluation, verification and clinical application. Results: A total of 184 individuals (average age 61.85 ± 13.25 years, 73.37% male) were enrolled, and the rate of VAP occurrence was found to be 57.07%. Factors such as the Glasgow Coma Scale (GCS) score, duration of stay in the Intensive Care Unit (ICU), dysphagia, Fazekas scale 2 and admission diastolic blood pressure were found to be associated with the occurrence of VAP in the nomogram that demonstrating a strong discriminatory power with AUC of 0.862 (95% CI, 0.810-0.914), and a favorable clinical net benefit. Conclusion: This nomogram, comprising GCS score, ICU duration, dysphagia, Fazekas scale 2 and admission diastolic blood pressure, can aid clinicians in predicting the identification of high-risk patients for VAP following endovascular treatment in large vessel occlusion stroke.

Endoplasmic reticulum-resident selenoproteins and their roles in glucose and lipid metabolic disorders.

Glucose and lipid metabolic disorders (GLMDs), such as diabetes, dyslipidemia, metabolic syndrome, nonalcoholic fatty liver disease, and obesity, are significant public health issues that negatively impact human health. The endoplasmic reticulum (ER) plays a crucial role at the cellular level for lipid and sterol biosynthesis, intracellular calcium storage, and protein post-translational modifications. Imbalance and dysfunction of the ER can affect glucose and lipid metabolism. As an essential trace element, selenium contributes to various human physiological functions mainly through 25 types of selenoproteins (SELENOs). At least 10 SELENOs, with experimental and/or computational evidence, are predominantly found on the ER membrane or within its lumen. Two iodothyronine deiodinases (DIOs), DIO1 and DIO2, regulate the thyroid hormone deiodination in the thyroid and some external thyroid tissues, influencing glucose and lipid metabolism. Most of the other eight members maintain redox homeostasis in the ER. Especially, SELENOF, SELENOM, and SELENOS are involved in unfolded protein responses; SELENOI catalyzes phosphatidylethanolamine synthesis; SELENOK, SELENON, and SELENOT participate in calcium homeostasis regulation; and the biological significance of thioredoxin reductase 3 in the ER remains unexplored despite its established function in the thioredoxin system. This review examines recent research advances regarding ER SELENOs in GLMDs and aims to provide insights on ER-related pathology through SELENOs regulation.

The resistance patterns and molecular characteristics of ESBL/AmpC-producing Escherichia coli from captive panda ecosystem in China.

Escherichia coli (E. coli) plays an important ecological role, and is a useful bioindicator to recognize the evolution of resistance in human, animal and environment. Recently, extended-spectrum ß-lactamases (ESBL) producing E.coli has posed a threat to public health. Generally, captive healthy giant pandas are not exposed to antibiotics; however, they still acquire antimicrobial resistant bacteria. In order to understand whether there is an exchange of resistance genes within the ecosystems of captive giant pandas, this study explored resistance characteristics of 330 commensal E. coli isolates from feces of giant pandas, the surroundings, and breeders. Isolates from different sources showed similar resistance phenotype, and ESBL/AmpC-producing isolates showed more profound resistance to antibiotics than non-ESBL/AmpC-producing isolates (P<0.05). Furthermore, the occurrence of broad-spectrum ß-lactamase related resistance genes and colistin resistance genes was detected, and isolates phylogenetic typing and multilocus sequence typing (MLST) were applied in this study. Seven different ß-lactamase resistance genes (blaCTX-M-55, blaCTX-M-15, blaCTX-M-27, blaCTX-M-65, blaTEM-1, blaOXA-1 and blaCMY) and mcr-1 were found in 68 ESBL/AmpC-producing isolates. blaCTX-M-55 (48.53 %) was found the most predominant resistance genes, followed by blaTEM-1 (19.12 %) and blaCTX-M-27 (16.18 %). Nonetheless, blaCTX-M-55 was commonly detected in the isolates from giant pandas (63.16 %), the surroundings (43.48 %), and breeders (33.33 %). However, there were no carbapenemase genes detected in this study. mcr-1 was harbored in only one isolate from giant panda. Forty-five tansconjugants were successfully obtained in the conjugation experiments. The presence of antimicrobial resistance and related resistance genes tested were observed in the transconjugants. The results indicated that 52.63 % of the isolates from giant panda 73.91 % of the isolates from surroundings, and 100 % of the isolates from breeders were phylogroup A. Total of 27 sequence types (ST) were recognized from the isolate by MLST and found that ST48 (19/68; 27.94 %) was the predominant ST type, especially in the isolates from giant pandas and the surroundings. In conclusion, commensal ESBL/AmpC-producing E. coli becomes a reservoir of ESBL resistance genes, which is a potential threaten to health of giant pandas. The interaction between giant pandas, surroundings and breeders contribute to development of resistant phenotypes and genotypes which might transfer across species or the surroundings easily; hence, strict monitoring based on a "One Health" approach is recommended.

The chain-mediating effect of Crp, BMI on the relationship between dietary intake of live microbes and hyperlipidaemia.

BACKGROUND: Inflammation and obesity are the risk factors for hyperlipidaemia. Nonetheless, research regarding the association between dietary live microbes intake and hyperlipidaemia is lacking. Therefore, this study focused on revealing the relationship between them and mediating roles of inflammation and obesity. METHODS: Totally 16,677 subjects were enrolled from the National Health and Nutrition Examination Survey (NHANES) (1999-2010 and 2015-2020). To explore the correlation between live microbes and hyperlipidaemia as well as blood lipid levels, respectively, multiple logistic regression and linear regression were employed. Furthermore, the mediating roles of body mass index (BMI), C-reactive protein (Crp) and their chain effect were explored through mediating analysis. RESULTS: High dietary live microbes intake was the protective factor for hyperlipidaemia. In addition, high dietary live microbes intake exhibited a positive relationship to the high-density lipoprotein cholesterol (HDL-C) among males (ß = 2.52, 95% CI: 1.29, 3.76, P < 0.0001) and females (ß = 2.22, 95% CI: 1.05, 3.38, P < 0.001), but exhibited a negative correlation with triglyceride (TG) levels in males (ß = -7.37, 95% CI: -13.16, -1.59, P = 0.02) and low-density lipoprotein cholesterol (LDL-C) levels in females (ß = -2.75, 95% CI: -5.28, -0.21, P = 0.02). Crp, BMI and their chain effect mediated the relationship between live microbes with HDL-C levels. Moreover, BMI and the chain effect mediated the relationship between live microbes with LDL-C levels. CONCLUSION: Dietary live microbes intake is related to a lower hyperlipidaemia risk. Crp, BMI and their chain effect make a mediating impact on the relationship.

Radical Three-Component Nitro Spiro-Cyclization of Unsaturated Sulfonamides/Amides to Access NO2-Featured 4-Azaspiro[4.5]decanes.

Free radical three-component nitration/spirocyclization of unsaturated sulfonamides/amides with tert-butyl nitrite was developed for the construction of diverse NO2-revised 4-azaspiro[4.5]decanes. This tandem system featured metal-free participation, simple operation, good selectivity/yields, and a green/low-cost O source. Meanwhile, one nitro-containing complex molecule and a scaled-up operation were performed well to test the synthetic potential of the cascade reaction. Isotopic labeling, radical inhibition experiments, and DFT analysis were carried out to gain insight into the reaction process.

Impact of health education on promoting influenza vaccination health literacy in primary school students: a cluster randomised controlled trial protocol.

INTRODUCTION: Influenza is a major public health threat, and vaccination is the most effective prevention method. However, vaccination coverage remains suboptimal. Low health literacy regarding influenza vaccination may contribute to vaccine hesitancy. This study aims to evaluate the effect of health education interventions on influenza vaccination rates and health literacy. METHODS AND ANALYSIS: This cluster randomised controlled trial will enrol 3036 students in grades 4-5 from 20 primary schools in Dongguan City, China. Schools will be randomised to an intervention group receiving influenza vaccination health education or a control group receiving routine health education. The primary outcome is the influenza vaccination rate. Secondary outcomes include health literacy levels, influenza diagnosis rate, influenza-like illness incidence and vaccine protection rate. Data will be collected through questionnaires, influenza surveillance and self-reports at baseline and study conclusion. ETHICS AND DISSEMINATION: Ethical approval has been sought from the Ethics Committee of the School of Public Health, Sun Yat-sen University. Findings from the study will be made accessible to both peer-reviewed journals and key stakeholders. TRIAL REGISTRATION NUMBER: NCT06048406.

Comparatively analysing the postoperative optical performance of different intraocular lenses: a prospective observational study.

BACKGROUND: Postoperative performance, including best corrected distance visual acuity (BCDVA) and optical metrics (from the OQAS and iTrace devices), was compared among 4 different intraocular lenses (IOLs). METHODS: This prospective observational study included 104 eyes from 104 subjects who underwent cataract surgery combined with implantation of 4 different IOLs: monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs and extended depth of focus (EDoF) IOLs. Postoperative BCDVA and optical metrics were collected at the 6th month. The OQAS optical metrics included the objective scattering index (OSI), Strehl ratio (SR), modulation transfer function (MTF) cut-off frequency, and predicted visual acuity (PVA); the iTrace optical metrics included blur/double vision, glare/halo, starburst, mixed focus, night myopia, and night hyperopia. RESULTS: There was no significant difference in BCDVA among the 4 groups (P = 0.059; power = 70.3%). Differences were observed in all OQAS optical metrics among the groups (all P < 0.001). Overall, Mon IOLs and EDoF IOLs exhibited better performance than Dif IOLs and SegRef IOLs. Starburst was the only iTrace optical metric that differed among the groups (P < 0.001): SegRef IOLs caused more starbursts than Mon IOLs (P = 0.001), Dif IOLs (P = 0.006) and EDoF IOLs (P < 0.001). Spearman rank correlation analysis was used to determine the relationships among the iTrace optical metrics, OQAS optical metrics and BCDVA: starburst was negatively correlated with BCDVA, PVA at contrasts of 100% and 20%, OSI, and MTF cut-off frequency (all P ≤ 0.001); mixed focus was positively correlated with BCDVA, PVA at contrasts of 100% and 20%, OSI, and MTF cut-off frequency (all P ≤ 0.001). CONCLUSIONS: Postoperative BCDVA and optical metrics varied among the different IOLs, which should be taken into account in the selection and management of IOLs for cataract patients. TRIAL REGISTRATION: This study was approved by the First Affiliated Hospital of Guangzhou Medical University Ethical Review Board (No. 50 2022).

Synthesis of ultrathin hybrid membranes via the co-polymerization of acrylic acid, styrene and molybdenum disulfide and their high adsorption selectivity for lead(II) in the mixture of metal ions.

Lead(II) is a potential carcinogen of heavy-metal ions (HIs). With the wide application of Pb-bearing products including lead alloy products, and new-energy lead-ion batteries, lead pollution has become a tricky problem. To solve such a difficulty, novel ultrathin MoS2-vinyl hybrid membranes (MVHMs) with a "spring" effect were synthesized via co-polymerization of acrylic acid, styrene and molybdenum disulfide (MoS2) and their adsorptions for HIs were explored. The "spring" effect derived from the interaction between the tendency of the short polyacrylic acid (PAA) chain connected with MoS2 to spread outward and the coulomb force between layers from MoS2 (s-MoS2), which enlarge the spacing of MoS2 layers without changing the number of layers after membrane formation, which changes the swelling membrane to a dense membrane and reduces the original thickness from 0.5 cm to 0.011 mm in the thickness direction. The adsorption experiment revealed that these MVHMs had super adsorption performance and high selectivity for Pb2+ by comparison with other five metal ions: Cu2+, Cd2+, Ni2+, Cr3+ and Zn2+. Especially, the adsorption quantity of MVHMs for Pb2+ could approach 2468 mg/g and the maximum adsorption ratio of qe[Pb2+]/qe[Cu2+] can reach 10.909. These values were much larger than the data obtained with the adsorbents reported in the last decade. A variety of models are applied to evaluate the effect of ionic groups. It was confirmed that -COOH plays a key role in adsorption of HIs and s-MoS2 also has a certain contribution. Conversely, ion exchange plays only a minor role during the period of adsorption process. Effective diffusion coefficient (Deff) of Pb(II) had the largest values among these metal ions. Hence, these hybrid membranes are promising adsorbents for the removal of Pb2+ from water containing various ions.

The Antioxidant, Anti-Inflammatory and Moisturizing Effects of Camellia oleifera Oil and Its Potential Applications.

Camellia oleifera oil (CO oil) extracted from C. oleifera seeds has a 2300-year consumption history in China. However, there is relatively little research regarding its non-edible uses. This study determined the physicochemical properties of CO oil extracted via direct pressing, identified its main components using GC-MS, and evaluated its antioxidant, moisturizing, and anti-inflammatory activities. The results revealed that CO oil's acid, peroxide, iodine, and saponification values were 1.06 ± 0.031 mg/g, 0.24 ± 0.01 g/100 g, 65.14 ± 8.22 g/100 g, and 180.41 ± 5.60 mg/g, respectively. CO oil's tocopherol, polyphenol, and squalene contents were 82.21 ± 9.07 mg/kg, 181.37 ± 3.76 mg/kg, and 53.39 ± 6.58 mg/kg, respectively; its unsaturated fatty acid (UFA) content was 87.44%, and its saturated fatty acid (SFA) content was 12.56%. CO oil also demonstrated excellent moisture retention properties, anti-inflammatory effects, and certain free radical scavenging. A highly stable CO oil emulsion with competent microbiological detection was developed using formulation optimization. Using CO oil in the emulsion significantly improved the formulation's antioxidant and moisturizing properties compared with those of the emulsion formulation that did not include CO oil. The prepared emulsion was not cytotoxic to cells and could reduce cells' NO content; therefore, it may have potential nutritional value in medicine and cosmetics.

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in ß cells. This upregulation increases both insulin secretion and susceptibility of ß cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Morphological study of superficial palmar arch and the significance in clinical operation.

BACKGROUND: The superficial palmar arch is a crucial blood supply to the palm. However, it exhibits significant variations, posing challenges in surgical procedures. Gaining a comprehensive understanding of the relationship between different types, physiological indices, and the clinical significance of the superficial palmar arch will enhance the accuracy of diagnosing and treating patients. MATERIALS AND METHODS: In this study, we dissected a total of 72 specimens, comprising 39 males and 33 females. We observed the type, length, and diameter of the superficial palmar arch and analyzed its correlation with the disease. Additionally, we conducted Doppler ultrasound measurements on 20 healthy volunteers (10 males and 10 females) and 18 patients with superficial palmar arch injury (10 males and 8 females) to assess the classification, diameter, intimal thickness, and blood flow velocity of the superficial palmar arch. We collected information on 9 male patients with finger fracture and observed the classification of the superficial palmar arch, fracture healing time, and basic function recovery time. Lastly, we analyzed rare variant specimens encountered during the anatomy process. RESULTS: In the exploration of human anatomy, there were four types of superficial palmar arch: ulnar artery arch type in 17 cases (23.61%), radial ulnar artery type in 46 cases (63.89%), ulnar artery without arch type in 6 cases (8.33%), and 3 cases (4.17%) of double arch type of radial and ulnar artery. One case non-arched type was found in imaging examination (5%). In one elderly male specimen, the hand's superficial palmar arch artery was tortuous and dilated. In addition, there was a positive correlation between the diameter and length of the superficial palmar arch (except the second common palmar digital artery in women), among which the ulnar artery and the third common palmar digital artery had the strongest correlation. Compared to healthy volunteers, patients with ulnar injury in the Radial-ulnar artery type exhibited a decrease in the diameter and blood flow velocity of the ulnar artery, as well as the second and third common palmar digital arteries. No such change was observed in patients with radial injury. Additionally, patients with ulnar injury in other types of Radial-ulnar artery also experienced a decrease in the diameter and blood flow velocity of the ulnar artery. Finger fracture patients with Ulnar artery with arch and Ulnar artery without arch had shorter fracture healing time and basic function recovery time compared to those with Radial-ulnar artery type. CONCLUSIONS: This study investigated the relationship between the classification, physiological index, and clinical significance of the superficial palmar arch at all levels. The results demonstrated that when the superficial palmar arch is damaged, it is important to consider both the classification and the site of damage, as this can potentially result in improved therapeutic outcomes. These findings provide a basis for future clinical research.

Self-assembled metal-phenolic nanocomplexes comprised of green tea catechin for tumor-specific ferroptosis.

Ferroptosis, a newly discovered form of regulated cell death, has garnered significant attention in the field of tumor therapy. However, the presence of overexpressed glutathione (GSH) and insufficient levels of H2O2 in the tumor microenvironment (TME) hinders the occurrence of ferroptosis. In response to these challenges, here we have constructed the self-assembled nanocomplexes (FeE NPs) utilizing epigallocatechin-3-gallate (EGCG) from green tea polyphenols and metal ions (Fe3+) as components. After grafting PEG, the nanocomplexes (FeE@PEG NPs) exhibit good biocompatibility and synergistically enhanced tumor-inhibitory properties. FeE@PEG NPs can be disassembled by H2O2 in the TME, leading to the rapid release of Fe3+ and EGCG. The released Fe3+ produces large amounts of toxic •OH by the Fenton reactions while having minimal impact on normal cells. The generated •OH effectively induces lipid peroxidation, which leads to ferroptosis in tumor cells. Meanwhile, the released EGCG can autoxidize to produce H2O2, which further promotes the production of •OH radicals and increases lipid peroxide levels. Moreover, EGCG also depletes the high levels of intracellular GSH, leading to an intracellular redox imbalance and triggering ferroptosis. This study provides new insights into advancing anticancer ferroptosis through rational material design, offering promising avenues for future research.

Intestinal microbiota and biliary system diseases.

Introduction: The incidence of biliary system diseases has been continuously increasing in the past decade. Biliary system diseases bring a heavy burden to humanity and society. However, the specific etiology and pathogenesis are still unknown. The biliary system, as a bridge between the liver and intestine, plays an indispensable role in maintaining the physiological metabolism of the body. Therefore, prevention and treatment of biliary diseases are crucial. It is worth noting that the microorganisms participate in the lipid metabolism of the bile duct, especially the largest proportion of intestinal bacteria. Methods: We systematically reviewed the intestinal microbiota in patients with gallstones (GS), non-calculous biliary inflammatory, and biliary tract cancer (BTC). And searched Pubmed, Embase and Web of science for research studies published up to November 2023. Results: We found that the abundance of Faecalibacterium genus is decreased in GS, primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and BTC. Veillonella, Lactobacillus, Streptococcus and Enterococcus genus were significantly increased in PSC, PBC and BTC. Interestingly, we found that the relative abundance of Clostridium was generally reduced in GS, PBC and BTC. However, Clostridium was generally increased in PSC. Discussion: The existing research mostly focuses on exploring the mechanisms of bacteria targeting a single disease. Lacking comparison of multiple diseases and changes in bacteria during the disease process. We hope to provide biomarkers forearly diagnosis of biliary system diseases and provide new directions for the mechanism of intestinal microbiota in biliary diseases.

Comparison of robot-assisted single-port-plus-one pyeloplasty vs. laparoscopic single-port pyeloplasty in the treatment of ureteropelvic junction obstruction in children.

Objective: To compare the efficacy of robot-assisted single-port-plus-one pyeloplasty (RSPY) and laparoscopic single-port pyeloplasty (LSPY) in the treatment of children with ureteropelvic junction obstruction (UPJO). Methods: The clinical data of 47 children who underwent surgery for UPJO at the Department of the Pediatric Surgery of the Fujian Provincial Hospital from October 2020 to September 2022 were analyzed retrospectively. Of these 47 children, 27 received RSPY while 20 underwent LSPY. The baseline data, operation time, intraoperative anastomosis time, intraoperative blood loss, postoperative hospital stay, complications, total cost, preoperative and postoperative renal parenchymal thickness (PT), anteroposterior renal pelvis diameter (APD), and differential renal function (DRF) of the two groups were compared to evaluate the clinical efficacy of the two surgical methods. Results: The results showed that both surgical techniques were successful and no patient transitioned to open surgery. There was no significant difference between the two groups in baseline data, intraoperative blood loss, complications, APD, and PT 6 months after surgery. There was also no significant difference in APD, PT, and DRF 12 months after surgery (all P > 0.05). Compared with the LSPY group, the RSPY group had shorter operation time [(153.04 ± 14.44) vs. (189.90 ± 32.59) min, t = -5.24, P < 0.05], less intraoperative anastomosis time [(68.81 ± 16.80) vs. (97.45 ± 11.99) min, t = -6.49, P < 0.05], shorter postoperative hospital stay [(5.96 ± 1.34) vs. (9.00 ± 1.33) d, t = -7.68, P < 0.05], but higher total cost [(57,390 ± 7,664) vs. (30,183 ± 4,219) yuan, t = 14.32, P < 0.05]. Conclusion: Compared with LSPY, RSPY achieves equivalent efficacy in the treatment of UPJO in children and has certain advantages by shortening the operation time, intraoperative anastomosis time, and postoperative hospital stay. However, its cost burden is heavy, and appropriate cases need to be selected for popularization and application.

Aptamer-mediated double strand displacement amplification with microchip electrophoresis for ultrasensitive detection of Salmonella typhimurium.

Rapid and quantitative detection of foodborne bacteria is of great significance to public health. In this work, an aptamer-mediated double strand displacement amplification (SDA) strategy was first explored to couple with microchip electrophoresis (MCE) for rapid and ultrasensitive detection of Salmonella typhimurium (S. Typhimurium). In double-SDA, a bacteria-identified probe consisting of the aptamer (Apt) and trigger sequence (Tr) was ingeniously designed. The aptamer showed high affinity to the S. Typhimurium, releasing the Tr sequence from the probe. The released Tr hybridized with template C1 chain, initiating the first SDA to produce numerous output strands (OS). The second SDA process was induced with the hybridization of the liberated OS and template C2 sequence, generating a large number of reporter strands (RS), which were separated and quantified through MCE. Cascade signal amplification and rapid separation of nucleic acids could be realized by the proposed double-SDA method with MCE, achieving the limit of detection for S. typhimurium down to 6 CFU/mL under the optimal conditions. Based on the elaborate design of the probes, the double-SDA assisted MCE strategy achieved better amplification performance, showing high separation efficiency and simple operation, which has satisfactory expectation for bacterial disease diagnosis.

Pyxinol Fatty Acid Ester Derivatives J16 against AKI by Selectively Promoting M1 Transition to M2c Macrophages.

Acute kidney injury (AKI) is a common, multicause clinical condition that, if ignored, often progresses to chronic kidney disease (CKD) and end-stage kidney disease, with a mortality rate of 40-50%. However, there is a lack of universal treatment for AKI. Inflammation is the basic pathological change of early kidney injury, and inflammation can exacerbate AKI. Macrophages are the primary immune cells involved in the inflammatory microenvironment of kidney disease. Therefore, regulating the function of macrophages is a crucial breakthrough for the AKI intervention. Our team chemically modified pyxinol, an ocotillol-type ginsenoside, to prepare PJ16 with higher solubility and bioavailability. In vitro, using a model of macrophages stimulated by LPS, it was found that PJ16 could regulate macrophage function, including inhibiting the secretion of inflammatory factors, promoting phagocytosis, inhibiting M1 macrophages, and promoting M1 transition to the M2c macrophage. Further investigation revealed that PJ16 may shield renal tubular epithelial cells (HK-2) damaged by LPS in vitro. Based on this, PJ16 was validated in the animal model of unilateral ureteral obstruction, which showed that it improves renal function and inhibits renal tissue fibrosis by decreasing inflammatory responses, reducing macrophage inflammatory infiltration, and preferentially upregulating M2c macrophages. In conclusion, our study is the first to show that PJ16 resists AKI and fibrosis by mechanistically regulating macrophage function by modulating the phenotypic transition from M1 to M2 macrophages, mainly M2c macrophages.

The biomechanical proteins different between low myopic corneas and moderate to high myopic corneas in human.

PURPOSE: To explore the biomechanical proteins different between low myopic corneas and moderate to high myopic corneas. METHODS: A total of 27 myopic corneas were used for the Tandem Mass Tag (TMT) proteomics analysis. Differentially expressed proteins (DEPs) were clustered with fold changes > 1.20 or < 0.83 and p < 0.05. Proteins and Proteins Interactions (PPIs) were conducted to find hub proteins; Uniprot database was to screen proteins with biomechanical functions, and Parallel Reaction Monitoring (PRM) was performed to verify the TMT results. Pearson analysis was used to reveal the correlations between myopic degrees and biomechanical proteins. The Immunofluorescence (IF) staining was used to observe the protein distributions. RESULTS: In total, 34 DEPs were observed between moderate myopic corneas and low myopic corneas; 103 DEPs were observed between high myopic corneas and low myopic corneas, 20 proteins overlapped. The PPIs analysis showed keratin 2, keratins 10 and PRSS1 were hub proteins. The Uniprot function analysis suggested keratin 2 and keratin 10 exhibited biomechanical functions. The PRM demonstrated keratin 2 and keratin 10 levels were significantly lower in moderate and high myopic corneas, which was consistent with the TMT proteomics results. IF staining also demonstrated keratin 2 and keratin 10 were less distributed in moderate and high myopic corneas than in low myopic corneas. CONCLUSIONS: The levels of biomechanical proteins keratin 2 and keratin 10 are significantly lower in moderate and high myopic corneas than in low myopic corneas.

TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer.

BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.