Corneal nerve changes by anti-glaucoma medications examined by in vivo confocal microscopy.

AIM: To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy (IVCM). METHODS: This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals. Among the glaucoma patients, 54 were treated with medication, while 25 remained untreated. Central corneal images were evaluated by IVCM, and then ACCMetrics was used to calculate the following parameters: corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman's rank correlation coefficient. RESULTS: The CNFD was reduced in glaucoma groups compared to healthy subjects (P<0.01). Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients. As the number of medications and usage count increased, CNFD, CNBD, CNFL, CTBD, CNFA, and CNFrD experienced a decline, while CNFW increased (all P<0.01). For the brinzolamide-therapy group, there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups (P<0.001). In the absence of medication, CNFD in males was lower than that in females (P<0.05). Among patients under medication therapy, CNFD remained consistent between males and females. CONCLUSION: Antiglaucoma eye drops affect the microstructure of corneal nerves. IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes.

Inserting colloidal quantum dots into GaN mesa-array subsurface porous structures through electrochemical etching for display color conversion application.

High-efficiency photon color conversion is an approach of great potential for implementing color display. Inspired by the observation of emission enhancement in a nanoscale cavity, a novel technique to fabricate an array of color converter by mixing colloidal quantum dots (QDs) with the electrolyte of an electrochemical etching (ECE) process is demonstrated. In this process, QDs flow with the electrolyte into the etched subsurface nanoscale porous structure (PS) and settle inside. Since the PS formation and hence QD insertion are controlled by the flow path of the applied electric current in the ECE process, this technique can be used for fabricating any graphic pattern. The nanostructure of such a QD-inserted mesa is examined to confirm QD insertion. Although only single-color mesa arrays are demonstrated in this paper, this technique can be used for fabricating a multiple-color mesa array if a QD or a light-emitting nanoparticle of higher thermal stability is available.

Activation of iron oxides through organic matter-induced dissolved oxygen penetration depth dynamics enhances iron-cycling driven ammonium oxidation in microaerobic granular sludge.

The iron redox cycle can enhance anammox in treating low-strength ammonia wastewater. However, maintaining an effective iron redox cycle and suppressing nitrite-oxidizing bacteria in a one-stage partial nitritation and anammox (PN/A) process poses challenges during long-term aeration. We proposed a novel and simple strategy to achieve an efficient iron redox cycle in an iron-mediated anoxic-microaerobic (A/O) process by controlling organic matter (OM) at medium-strength levels (30-110 mg COD/L) in microaerobic granular sludge (MGS)-dominated reactor. The developed A/O process consistently achieved >90 % OM removal and >75 % nitrogen removal. Medium-strength OM varied the penetration depths of dissolved oxygen (DO) in MGS, regulating redox conditions and promoting redox reactions across MGS layers, thus activating accumulated inert iron oxides. Ammonia-oxidizing bacteria (Nitrosomonas), iron-reducing bacteria (e.g., Ignavibacterium, Geobacter), and anammox bacteria (Ca. Kuenenia) coexisted harmoniously in MGS. This coexistence ensured high anammox and Feammox rates along with a robust iron redox cycle, thereby mitigating the adverse impacts of fluctuating DO and OM on one-stage PN/A process stability. The identification of iron reduction-associated genes within Ca. Kuenenia, Ignavibacterium, and Geobacter suggests their potential roles in supporting Feammox coupled in one-stage PN/A process. This study introduces an iron-cycle-driven A/O process as an energy-efficient alternative for simultaneous carbon and nitrogen removal from low-strength wastewater.

Mendelian randomization analysis reveals causal effects of blood lipidome on gestational diabetes mellitus.

BACKGROUND: Observational studies have revealed associations between maternal lipid metabolites and gestational diabetes mellitus (GDM). However, whether these associations are causal remain uncertain. OBJECTIVE: To evaluate the causal relationship between lipid metabolites and GDM. METHODS: A two-sample Mendelian randomization (MR) analysis was performed based on summary statistics. Sensitivity analyses, validation analyses and reverse MR analyses were conducted to assess the robustness of the MR results. Additionally, a phenome-wide MR (Phe-MR) analysis was performed to evaluate potential side effects of the targeted lipid metabolites. RESULTS: A total of 295 lipid metabolites were included in this study, 29 of them had three or more instrumental variables (IVs) suitable for sensitivity analyses. The ratio of triglycerides to phosphoglycerides (TG_by_PG) was identified as a potential causal biomarker for GDM (inverse variance weighted (IVW) estimate: odds ratio (OR) = 2.147, 95% confidential interval (95% CI) 1.415-3.257, P = 3.26e-4), which was confirmed by validation and reverse MR results. Two other lipid metabolites, palmitoyl sphingomyelin (d18:1/16:0) (PSM(d18:1/16:0)) (IVW estimate: OR = 0.747, 95% CI 0.583-0.956, P = 0.021) and triglycerides in very small very low-density lipoprotein (XS_VLDL_TG) (IVW estimate: OR = 2.948, 95% CI 1.197-5.215, P = 0.015), were identified as suggestive potential biomarkers for GDM using a conventional cut-off P-value of 0.05. Phe-MR results indicated that lowering TG_by_PG had detrimental effects on two diseases but advantageous effects on the other 13 diseases. CONCLUSION: Genetically predicted elevated TG_by_PG are causally associated with an increased risk of GDM. Side-effect profiles indicate that TG_by_PG might be a target for GDM prevention, though caution is advised due to potential adverse effects on other conditions.

Mining unique cysteine synthetases and computational study on thoroughly eliminating feedback inhibition through tunnel engineering.

L-cysteine is an essential component in pharmaceutical and agricultural industries, and synthetic biology has made strides in developing new metabolic pathways for its production, particularly in archaea with unique O-phosphoserine sulfhydrylases (OPSS) as key enzymes. In this study, we employed database mining to identify a highly catalytic activity OPSS from Acetobacterium sp. (AsOPSS). However, it was observed that the enzymatic activity of AsOPSS suffered significant feedback inhibition from the product L-cysteine, exhibiting an IC50 value of merely 1.2 mM. A semi-rational design combined with tunnel analysis strategy was conducted to engineer AsOPSS. The best variant, AsOPSSA218R was achieved, totally eliminating product inhibition without sacrificing catalytic efficiency. Molecular docking and molecular dynamic simulations indicated that the binding conformation of AsOPSSA218R with L-cys was altered, leading to a reduced affinity between L-cysteine and the active pocket. Tunnel analysis revealed that the AsOPSSA218R variant reshaped the landscape of the tunnel, resulting in the construction of a new tunnel. Furthermore, random acceleration molecular dynamics simulation and umbrella sampling simulation demonstrated that the novel tunnel improved the suitability for product release and effectively separated the interference between the product release and substrate binding processes. Finally, more than 45 mM of L-cysteine was produced in vitro within 2 h using the AsOPSSA218R variant. Our findings emphasize the potential for relieving feedback inhibition by artificially generating new product release channels, while also laying an enzymatic foundation for efficient L-cysteine production.

Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a common consequence of radical partial hepatectomy in hepatocellular carcinoma (HCC). AIMS: To investigate the relationship between preoperative antiviral therapy and PHLF, as well as assess the potential efficacy of hepatitis B virus (HBV) DNA level in predicting PHLF. METHODS: A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy. Receiver operating characteristic (ROC) analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses. Logistic regression analyses were performed to assess the independent risk factors of PHLF. The increase in the area under the ROC curve, categorical net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to quantify the efficacy of HBV DNA level for predicting PHLF. The P < 0.05 was considered statistically significant. RESULTS: Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF (P < 0.05). HBV DNA level with an optimal cutoff value of 269 IU/mL (P < 0.001) was an independent risk factor of PHLF. All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve, categorical NRI, and IDI, particularly for the fibrosis-4 model, with values of 0.729 (95%CI: 0.705-0.754), 1.382 (95%CI: 1.341-1.423), and 0.112 (95%CI: 0.110-0.114), respectively. All the above findings were statistically significant. CONCLUSION: In summary, preoperative antiviral treatment can reduce the incidence of PHLF, whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

Central precocious puberty should be taken seriously in children with Leydig cell tumors of the testis after surgical treatment: a tertiary center experience.

ABSTRACT: Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children's Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40-140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1-6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.

Structure and performance regulation of energetic complexes through multifunctional molecular self-assembly.

The design of novel energetic compounds constitutes a pivotal research direction within the field of energetic materials. However, exploring the intricate relationship between their molecular structure and properties, in order to uncover their potential applications, remains a challenging endeavor. Therefore, employing multi-molecule assembly techniques to modulate the structure and performance of energetic materials holds immense significance. This approach enables the creation of a new generation of energetic materials, fueling research and development efforts in this field. In this study, a series of coordination compounds are synthesized by utilizing tetranitroethide (TNE) as an anion, which possesses a high nitrogen and oxygen content. The synthesis involves the synergistic modification between metal ions and small molecule ligands. Characterization of the obtained compounds is carried out using various techniques, including single crystal X-ray diffraction, IR spectroscopy, elemental analysis, and simultaneous TG-DSC analysis. Additionally, the energy of formation for these compounds is calculated using bomb calorimetry, based on the heat of combustion. The detonation performances of the compounds are determined through calculations using the EXPLO 5 software, and their sensitivities to external stimuli are evaluated.

Lower fecal microbiota transplantation ameliorates ulcerative colitis by eliminating oral-derived Fusobacterium nucleatum and virulence factor.

BACKGROUND: Recently, the oral oncobacterium Fusobacterium nucleatum (F. nucleatum), has been linked with ulcerative colitis (UC). Here, we aim to investigate whether Fecal Microbiota Transplantation (FMT) can alleviate UC by restoring gut microbiota and eliminating oral-derived F. nucleatum and virulence factor fadA. METHOD: C57BL/6J mice were randomly divided into a healthy control group (HC), Dextran Sulfate Sodium group (DSS), oral inoculation group (OR), upper FMT group (UFMT), and lower FMT group (LFMT). Disease activity index, body weight, survival rate, and histopathological scores were used to measure the severity of colitis. The function of the intestinal mucosal barrier was evaluated by performing immunohistochemical staining of the tight junction protein Occludin. Real-time PCR was used to assess the relative abundance of the nusG gene and the virulence gene fadA. Cytokine levels were detected by ELISA. Full-length sequencing of 16S rRNA was used to analyze the changes and composition of gut microbiota. FINDINGS: Oral incubation of F. nucleatum further exacerbated the severity of colitis and gut dysbiosis. Peptostreptococcaceae, Enterococcaceae, and Escherichia coli were significantly enriched in OR mice. However, LFMT mice showed an obvious decrease in disease activity and were more effective in restoring gut microbiota and eliminating F. nucleatum than UFMT mice. Bacteroidota, Lachnospiraceae, and Prevotellaceae were mainly enriched bacteria in LFMT mice. In addition, Genera such as Lactobacillus, Allobaculum, and Bacteroidales were found negative correlation with TNF-α, IL-1ß, and IL-6. Genera like Romboutsia, Escherichia Shigella, Enterococcus, and Clostridium were found positively correlated with TNF-α, IL-1ß, and IL-6. CONCLUSIONS: Oral incubation of F. nucleatum further exacerbates the severity and dysbiosis in DSS-induced colitis mice. Besides, lower tract FMT can ameliorate colitis by restoring the gut microbiota diversity and eliminating F. nucleatum and virulence factor fadA.

[Factors affecting the postoperative prognosis of penile cancer].

OBJECTIVE: To investigate the risk factors affecting the prognosis of penile cancer after surgery. METHODS: We retrospectively analyzed the clinical data on 112 cases of penile cancer treated in Weifang People's Hospital from January 2013 to December 2023. Using the Kaplan-Meier survival curve, χ2 test, Fisher's exact test, and univariate and multivariate Cox risk regression analyses, we compared the clinical characteristics among different groups, and determined the independent prognostic risk factors for cancer-specific survival (CSS) of the patients. RESULTS: The 1-, 3- and 5-year CSS rates of the penile cancer patients were 78.2%, 66.1% and 63.7%, respectively. Kaplan-Meier analysis indicated a significant correlation of a higher neutrophil-to-lymphocyte ratio (NLR) with a lower CSS rate (P < 0.001). Multivariate Cox regression analysis showed high NLR (HR = 2.6; 95% CI: 1.031－6.558; P = 0.043) to be an independent risk factor for CSS. CONCLUSION: Preoperative NLR is an independent risk factor for the prognosis of penile cancer. In addition, older age, farmer or worker occupation, lower education, preoperative lymphocyte-to-monocyte ratio (LMR)≤2.81, preoperative fibrinogen (FIB)≥3.41 g/L, advanced tumor stage and tumor differentiation are associated with the poor prognosis the malignancy.

Oxysulfonylation of Alkynes with Sodium Sulfinates to Access ß-Keto Sulfones Catalyzed by BF3·OEt2.

An efficient and operationally simple method for the synthesis of ß-keto sulfones through the BF3·OEt2-promoted reaction of alkynes and sodium sulfinates is developed. With its facile and selective access to the targets, it features good functional group compatibility, mild conditions, easily available starting materials, and good yields. Notably, the reaction does not require metal catalysts or chemical reagents with pungent odors.

The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity: A Meta-Analysis.

Objective: Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on asthma, which is often comorbid with type 2 diabetes mellitus (T2DM) and obesity. Therefore, we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1 (GLP-1) receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. Methods: PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were systematically searched from inception to July 2023. Randomized controlled trials (RCTs) of GLP-1 receptor-based agonists (GLP-1RA, GLP-1 based dual and triple receptor agonist) with reports of asthma events were included. Outcomes were computed as risk ratios ( RR) using a fixed-effects model. Results: Overall, 39 RCTs with a total of 85,755 participants were included. Compared to non-GLP-1 receptor-based agonist users, a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments, although the difference was not statistically significant [ RR = 0.91, 95% confidence interval ( CI): 0.68 to 1.24]. Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users ( RR = 0.65, 95% CI: 0.43 to 0.99, P = 0.043). We also performed sensitivity analyses for participant characteristics, study design, drug structure, duration of action, and drug subtypes. However, no significant associations were observed. Conclusion: Compared with non-users, a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments. Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Shear wave elastography of transverse carpal ligament increased with simulated carpal tunnel pressure.

BACKGROUND: Elevation of carpal tunnel pressure is known to be associated with carpal tunnel syndrome. This study aimed to correlate the shear wave elastography in the transverse carpal ligament (TCL) with carpal tunnel pressures using a cadaveric model. METHODS: Eight human cadaveric hands were dissected to evacuate the tunnels. A medical balloon was inserted into each tunnel and connected to a pressure regulator to simulate tunnel pressure in the range of 0-210 mmHg with an increment of 30 mmHg. Shear wave velocity and modulus was measure in the middle of TCL. RESULTS: SWV and SWE were significantly dependent on the pressure levels (p < 0.001), and positively correlated to the tunnel pressure (SWV: R = 0.997, p < 0.001; SWE: R = 0.996, p < 0.001). Regression analyses showed linear relationship SWV and pressure (SWV = 4.359 + 0.0263 * Pressure, R2 = 0.994) and between SWE and pressure (SWE = 48.927 + 1.248 * Pressure, R2 = 0.996). CONCLUSION: The study indicated that SWV and SWE in the TCL increased linearly as the tunnel pressure increased within the current pressure range. The findings suggested that SWV/SWE in the TCL has the potential for prediction of tunnel pressure and diagnosis of carpal tunnel syndrome.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma.

Hepatic artery infusion chemotherapy (HAIC) has good clinical efficacy in the treatment of advanced hepatocellular carcinoma (HCC); however, its efficacy varies. This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications. As of October 25, 2023, 51 articles have been retrieved based on keyword predictions and HAIC. Sixteen eligible articles were selected for inclusion in this study. Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing, gene testing, and imaging testing. The above indicators and their combined forms showed excellent predictive effects in retrospective studies. This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC, analyzed each marker's ability to predict HAIC efficacy, and provided a reference for the clinical application of the prediction system.

The comparison of white-to-white via triple person-times caliper measuring and machine-measuring in V4c implantable collamer lens implantation.

This study aimed to compare the differences and characteristics of white-to-white (WTW) values obtained before V4c implantation using triple person-times caliper, IOL-Master 700, Pentacam HR, and UBM, and to assess their correlation with vaulting. A total of 930 myopia patients (1842 eyes) who were interested in undergoing ICL surgery were assessed before the procedure using various instruments. The WTW measurements were obtained using a triple person-times caliper, Pentacam HR, and IOL-Master 700, whereas the angle-to-angle (ATA) measurements were obtained using UBM. The size of the ICL was subsequently calculated using triple person-times caliper measurements. The vault of the ICL was assessed using Pentacam HR three months after the surgery. The WTW was determined to be 11.30 ± 0.29 mm, 11.43 ± 0.29 mm, and11.86 ± 0.38 mm, respectively, using the triple person-times caliper, Pentacam HR, and IOL-Master 700. The measurement of ATA was 11.57 ± 0.51 mm, as done by UBM. The ICL vault was measured to be 400.97 ± 198.46 µm when examined with Pentacam HR three monthsafter the procedure. The linear regression analyses of ICL size and WTW of triple person-times caliper, ICL vault and WTW were (R = 0.703, p < 0.001; R = 0.0969, p < 0.001) respectively. The highest correlation was found between IOL-Master and Pentacam HR (r = 0.766, p = 0.000). The lowest correlation was found between UBM and Pentacam HR (r = 0.358, p = 0.002). Bland-Altman analysis showed that the 95% limits of agreement (LoA) were the triple person-times caliper and Pentacam HR (- 0.573, 0.298) and the triple person-times caliper and UBM (- 1.15, - 0.605). This indicated a strong agreement between the triple person-times caliper and Pentacam HR and a lack of agreement between the triple person-times caliper and UBM. Triple person-times caliper measurements offer excellent maneuverability, practicality, and reliable outcomes for determining ICL vaults. Measurements obtained using the triple-person caliper were less differece than those obtained using the Pentacam HR.

[Radial growth response of Populus euphratica to climate change in the Cele desert oasis ecotone, China]. / ç­–å‹’æ²™æ¼ ç»¿æ´²è¿‡æ¸¡å¸¦èƒ¡æ¨å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Populus euphratica is an important tree species in the arid regions of Northwest China, which is sensitive to climate changes. Climate of the Northwest China is changing to be "warm and humid", but how it would affect the regional forest growth is not clear. In this study, the radial growth response of P. euphratica to major climatic factors and their temporal changes during 1984-2021 were analyzed by using dendrochronology method in the desert oasis ecotone of Cele in the southern Tarim basin. The results showed that tree-ring width index of P. euphratica had a significant negative correlation with temperature in September of the previous year, and in February and May of current year, had significant positive correlation with precipitation in September of previous year and March and May of current year, and had significant positive correlations with SPEI in February and May of current year. The relationships between tree-ring width index and combined month climatic factors were more obvious. The results of moving correlation analysis showed that the correlation between tree-ring width index and temperature in the growing season tended to be strengthened in recent years, while the correlation between tree-ring width index and precipitation, SPEI tended to be declined or remain stable. The variations of the relationships between tree-ring width index and combined month climatic factors were more obvious compared that with single month. Current regional climate is conducive to the growth and development, as well as the improvement of ecological shelter function of P. euphratica forest in the desert oasis ecotone of Cele.