Directed Self-Assembly of Polystyrene-Block-Polyhedral Oligomeric Silsesquioxane Monolayer by Nano-Trench for Nanopatterning.

This work pioneers to combine fast self-assembly of polyhedral oligomeric silsesquioxanes (POSS) nanocage-based giant surfactants with high etching contrast and directed self-assembly for reliable long-range lateral order to create well-aligned sub-10 nm line nanopatterns via reactive ion etching (RIE). Polystyrene-block-oligo(dimethylsiloxane) substituted POSS (PS-b-oDMS7POSS) with seven oligo(dimethylsiloxane) at the corners of the POSS nanocage and one polystyrene (PS) tail is designed and synthesized as a giant surfactant with self-assembly behaviors like block copolymer (BCP). In contrast to BCP, oDMS7POSS gives a volume-persistent "nanoatom" particle with higher mobility for fast self-assembly and higher segregation strength with PS for smaller feature size. By taking advantage of directed self-assembly using nano-trench fabricated by electron beam lithography, well-ordered nanostructured monolayer with well-aligned parallel oDMS7POSS cylinders can be formed by confined self-assembly within the nano-trench. With the optimization of the RIE treatment using O2 as an etchant, the high etching contrast from the oDMS7POSS and PS gives the formation of well-defined line nanopatterns with sub-10 nm critical dimension that can serve as a mask for pattern transfer in lithography. These results demonstrate a cost-effective approach for nanopatterning by utilizing a creatively designed giant surfactant with sub-10 nm feature size and excellent etching contrast for modern lithographic applications.

Altered connectivity of central autonomic network: effects of dysautonomia in hereditary transthyretin amyloidosis with polyneuropathy.

BACKGROUND: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN. METHODS: Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed. RESULTS: Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability. CONCLUSIONS: Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

The Therapeutic Role of NPS-1034 in Pancreatic Ductal Adenocarcinoma as Monotherapy and in Combination with Chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in terms of diagnosis and treatment, with limited therapeutic options and a poor prognosis. This study explored the potential therapeutic role of NPS-1034, a kinase inhibitor targeting MET and AXL, in PDAC. The investigation included monotherapy with NPS-1034 and its combination with the commonly prescribed chemotherapy agents, fluorouracil and oxaliplatin. Our study revealed that NPS-1034 induces cell death and reduces the viability and clonogenicity of PDAC cells in a dose-dependent manner. Furthermore, NPS-1034 inhibits the migration of PDAC cells by suppressing MET/PI3K/AKT axis-induced epithelial-to-mesenchymal transition (EMT). The combination of NPS-1034 with fluorouracil or oxaliplatin demonstrated a synergistic effect, significantly reducing cell viability and inducing tumor cell apoptosis compared to monotherapies. Mechanistic insights provided by next-generation sequencing indicated that NPS-1034 modulates immune responses by inducing type I interferon and tumor necrosis factor production in PDAC cells. This suggests a broader role for NPS-1034 beyond MET and AXL inhibition, positioning it as a potential immunity modulator. Overall, these findings highlight the anticancer potential of NPS-1034 in PDAC treatment in vitro, both as a monotherapy and in combination with traditional chemotherapy, offering a promising avenue for further in vivo investigation before clinical exploration.

Ab initio MO study on direct production of H2O, N2O and CO3 from the respective CH2OO "Bee-sting-like" attack at H2, N2 and CO2.

CONTEXT: We have computationally elucidated the mechanism for formation of H2O, N2O and CO3 from the reactions of CH2OO with H2, N2 and CO2, respectively, by the direct attack of the terminal O atom of CH2OO. This unique mechanism, which is characteristically "bee-sting-like" in nature, was found to be closely parallel to their reactions with the O(1D) atom. Reactions with H2 and CO2 take place by side-on attack, while the N2 reaction occurs by end-on attack with predicted barriers, 19.4, 13.1 and 25.3 kcal.mol-1, respectively. The CO2 reaction with CH2OO was found to occur by producing the C2v CO3, O = C < (O)O, instead of its D3h conformer, essentially similar to the O(1D) + CO2 reaction. The rate constants for the three reactions have been computed by the transition state theory (TST) based on the predicted potential energy profiles. We have also utilized the isodesmic nature of the dative bond exchange in the N2 reaction, CH2O → O + N2 = CH2O + N2 → O, to estimate the heat of the formation of CH2OO. Based on the heat of reaction computed at the highest level of theory employed, we obtained ΔfHo0 (CH2OO) = 27.5 kcal.mol-1; the value agrees with the recent results within ± 1 kcal.mol-1. METHODS: All calculations were performed using Gaussian 16 software. Geometry, frequency, and IRC analysis calculations were conducted at the M06-2X/aug-cc-pVTZ level of theory. The heats of reaction have been evaluated at the highest level, CCSD(T)/CBS(T,Q,5)//M06-2x/aug-cc-pvTz.

Predicting Sprint Performance From the Vertical and Horizontal Jumps in National Football League Combine Athletes.

ABSTRACT: Agar-Newman, DJ, MacRae, F, Tsai, M-C, and Klimstra, M. Predicting sprint performance from the vertical and horizontal jumps in National Football League Combine athletes. J Strength Cond Res 38(8): 1433-1439, 2024-Identifying fast athletes is an important part of the National Football League (NFL) Combine. However, not all athletes partake in the 36.58-m sprint, and relying on this single test may miss potentially fast athletes. Therefore, the purpose of this study was to determine whether sprinting times can be predicted using simple anthropometric and jumping measures. Data from the NFL Combine between the years 1999-2020 inclusive were used (n = 4,149). Subjects had a mean (±SD) height = 1.87 ± 0.07 m and body mass = 111.96 ± 20.78 kg. The cross-validation technique was used, partitioning the data into a training set (n = 2,071) to develop regression models to predict time over the 9.14-, 9.14- to 18.29-, 18.29- to 36.58-m, and 36.58-m segments using vertical jump, broad jump, height, and mass as the independent variables. The models were then evaluated against a test set (n = 2,070) for agreement. Statistically significant (p < 0.01) models were determined for 9.14-m time (adjusted R2 = 0.76, SEE = 0.05 seconds), 9.14- to 18.29-m time (adjusted R2 = 0.74, SEE = 0.04 seconds), 18.29- to 36.59-m time (adjusted R2 = 0.79, SEE = 0.07 seconds), and 36.58-m time (adjusted R2 = 0.84, SEE = 0.12 seconds). When evaluated against the test set, the models showed biases of -0.05, -0.04, -0.02, and -0.02 seconds and root-mean-square error of 0.07, 0.05, 0.07, and 0.12 seconds for the 9.14-, 9.14- to 18.29-, 18.29- to 36.58-m, and 36.58-m segments, respectively. However, 5-6% of the predictions lay outside of the limits of agreement. This study provides 4 formulae that can be used to predict sprint performance when the 36.58-m sprint test is not performed, and practitioners can use these equations to determine training areas of opportunity when working with athletes preparing for the NFL Combine.

Ab Initio Chemical Kinetics for Oxidation of CH3OH by N2O4: Elucidation of the Mechanism for Major Product Formation and Its Relevancy to Tropospheric Chemistry.

Next to CH4, CH3OH is the most abundant C1 organics in the troposphere. The redox reaction of CH3OH with N2O4 had been shown experimentally to produce CH3ONO, instead of CH3ONO2. The mechanism for the reaction remains unknown to date. We have investigated the reaction by ab initio MO calculations at the UCCSD(T)/6-311+G(3df,2p)//UB3LYP/6-311+G(3df,2p) level. The result indicates that the reaction takes place primarily by the isomerization of N2O4 to ONONO2 through a very loose transition state within the N2O4-CH3OH collision complex with a 14.3 kcal/mol barrier, followed by the rapid attack of ONONO2 at CH3OH producing CH3ONO and HNO3. The predicted mechanism for the redox reaction compares closely with the hydrolysis of N2O4. The computed rate constant, k1 = 1.43 × 10-8 T1.96 exp (-9092/T) (200-2000 K) cm3molecule-1s-1, for the formation of CH3ONO and HNO3 agrees reasonably with available low-temperature kinetic data and is found to be similar to that of the isoelectronic N2O4 + CH3NH2 reaction. We have also estimated the kinetics for the termolecular reaction, 2 NO2 + CH3OH, and compared it with the direct bimolecular process; the latter was found to be 4.4 × 105 times faster under the troposphere condition. On the basis of the known pollution levels of NO2, N2O4, and CH3OH, both processes were estimated to be of negligible importance to tropospheric chemistry, however.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway.

BACKGROUND: CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors, including gastric cancer (GC), and is associated with tumor progression and immune infiltration; however, the roles and mechanisms of CALD1 in epithelial-mesenchymal transition (EMT) in GC are unknown. AIM: To investigate the role and mechanism of CALD1 in GC progression, invasion, and migration. METHODS: In this study, the relationship between CALD1 and GC, as well as the possible network regulatory mechanisms of CALD1, was investigated by bioinformatics and validated by experiments. CALD1-siRNA was synthesized and used to transfect GC cells. Cell activity was measured using the CCK-8 method, cell migration and invasive ability were measured using wound healing assay and Transwell assay, and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot. A GC cell xenograft model was established to verify the results of in vitro experiments. RESULTS: Bioinformatics results showed that CALD1 was highly expressed in GC tissues, and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC. The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression, and a prognostic model was constructed and evaluated. The experimental results were consistent with the results of the bioinformatics analysis. The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1, with the strongest expression found in AGS and MKN45 cells. Cell activity was significantly reduced after CALD1-siRNA transfection of AGS and MKN45 cells. The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection, and the related mRNA and protein expression was altered. According to bioinformatics findings in GC samples, the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway, and was closely related to the PI3K-Akt signaling pathway. Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K, p-AKT, and p-mTOR, members of the PI3K-Akt pathway,while decreasing the expression of PTEN; PI3K-Akt inhibitor treatment decreased the expression of PI3K, p-AKT, and p-mTOR in cells overexpressing CALD1 (still higher than that in the normal group), but increased the expression of PTEN (still lower than that in the normal group). CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor. Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor. The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1, whereas the effect of overexpression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor. Animal experiments showed that tumour growth was slow after inhibition of CALD1, and the expression of some PI3K-Akt and EMT pathway proteins was altered. CONCLUSION: Increased expression of CALD1 is a key factor in the progression, invasion, and metastasis of GC, which may be associated with regulating the PI3K-Akt pathway to promote EMT.

Constructing B─N─P Bonds in Ultrathin Holey g-C3N4 for Regulating the Local Chemical Environment in Photocatalytic CO2 Reduction to CO.

The lack of intrinsic active sites for photocatalytic CO2 reduction reaction (CO2RR) and fast recombination rate of charge carriers are the main obstacles to achieving high photocatalytic activity. In this work, a novel phosphorus and boron binary-doped graphitic carbon nitride, highly porous material that exhibits powerful photocatalytic CO2 reduction activity, specifically toward selective CO generation, is disclosed. The coexistence of Lewis-acidic and Lewis-basic sites plays a key role in tuning the electronic structure, promoting charge distribution, extending light-harvesting ability, and promoting dissociation of excitons into active carriers. Porosity and dual dopants create local chemical environments that activate the pyridinic nitrogen atom between the phosphorus and boron atoms on the exposed surface, enabling it to function as an active site for CO2RR. The P-N-B triad is found to lower the activation barrier for reduction of CO2 by stabilizing the COOH reaction intermediate and altering the rate-determining step. As a result, CO yield increased to 22.45 µmol g-1 h-1 under visible light irradiation, which is ≈12 times larger than that of pristine graphitic carbon nitride. This study provides insights into the mechanism of charge carrier dynamics and active site determination, contributing to the understanding of the photocatalytic CO2RR mechanism.

Characterization of Microbotryum lychnidis-dioicae Secreted Effector Proteins, Their Potential Host Targets, and Localization in a Heterologous Host Plant.

Microbotryum lychnidis-dioicae is an obligate fungal species colonizing the plant host, Silene latifolia. The fungus synthesizes and secretes effector proteins into the plant host during infection to manipulate the host for completion of the fungal lifecycle. The goal of this study was to continue functional characterization of such M. lychnidis-dioicae effectors. Here, we identified three putative effectors and their putative host-plant target proteins. MVLG_02245 is highly upregulated in M. lychnidis-dioicae during infection; yeast two-hybrid analysis suggests it targets a tubulin α-1 chain protein ortholog in the host, Silene latifolia. A potential plant protein interacting with MVLG_06175 was identified as CASP-like protein 2C1 (CASPL2C1), which facilitates the polymerization of the Casparian strip at the endodermal cells. Proteins interacting with MVLG_05122 were identified as CSN5a or 5b, involved in protein turnover. Fluorescently labelled MVLG_06175 and MVLG_05122 were expressed in the heterologous plant, Arabidopsis thaliana. MVLG_06175 formed clustered granules at the tips of trichomes on leaves and in root caps, while MVLG_05122 formed a band structure at the base of leaf trichomes. Plants expressing MVLG_05122 alone were more resistant to infection with Fusarium oxysporum. These results indicate that the fungus might affect the formation of the Casparian strip in the roots and the development of trichomes during infection as well as alter plant innate immunity.

Postvaccination serosurveillance of foot-and-mouth disease through virus-neutralizing and nonstructural protein antibody tests on pig farms in Taiwan: 2009-2020.

The use of virus-neutralizing (VN) and nonstructural protein (NSP) antibody tests in a serosurveillance program for foot-and-mouth disease (FMD) can identify pig herds that are adequately vaccinated, with a high percentage of pigs with VN positive antibody titers; these tests can also help identify pigs with NSP-positivity that have previously been or are currently infected even in vaccinated herds. To identify infected herds and manage infection, the combination of VN and NSP antibody tests was used in Taiwan's serosurveillance program implemented simultaneously with the compulsory FMD vaccination program. The result was the eradication of FMD: Taiwan was recognized by the World Organization for Animal Health as an FMD-free country without vaccination in 2020. Evaluation of the compulsory vaccination program incorporated in the FMD control program in Taiwan revealed that the vaccine quality was satisfactory and the vaccination program was effective during the period of compulsory vaccination (2010-2017). Sound immunological coverage was achieved, with 89.1% of pigs having VN antibody titers exceeding 1:16 in 2016. This level of immunological coverage would be expected to substantially reduce or prevent FMD transmission, which was borne out by the results of the NSP tests. We identified farms having positive NSP reactors (very low annual prevalence) before the cessation of FMD vaccination in July 2018; however, detailed serological and clinical investigations of pigs of all ages in suspect herds demonstrated that no farms were harboring infected animals after the second half of 2013. Thus, the results revealed no evidence of FMD circulation in the field, and Taiwan regained FMD-free status.

Analysis of outcomes and prognostic factor in acute type A aortic dissection complicated with preoperative shock: A single-center study.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a critical cardiovascular emergency that requires prompt surgical intervention for preserving life, particularly in patients with critical preoperative status. This retrospective study aimed to investigate the clinical features, early and late outcomes, and prognostic factors in patients undergoing aortic repair surgery for ATAAD complicated with preoperative shock. METHODS: Between April 2007 and July 2020, 694 consecutive patients underwent emergency ATAAD repair at our institution, including 162 (23.3%) presenting with preoperative shock (systolic blood pressure <90 mm Hg), who were classified into the survivor (n = 125) and non-survivor (n = 37) groups according to whether they survived to hospital discharge. The clinical demographics, surgical information, and postoperative complications were compared. Five-year survival and freedom from reoperation rates of survivors were analyzed using the Kaplan-Meier actuarial method. Multivariate logistic regression analysis was used to identify independent risk factors for in-hospital mortality. RESULTS: The in-hospital surgical mortality rate in patients with ATAAD and shock was 22.8%. The non-survivor group showed higher rates of preoperative cardiopulmonary resuscitation, acute myocardial infarction, and cerebral infarction, and was associated with longer cardiopulmonary bypass time, higher rates of total arch replacement and intraoperative extracorporeal membrane oxygenation implementation. The non-survivor group had higher blood transfusion volumes and rates of malperfusion-related complications. Multivariate analysis revealed that preoperative cardiopulmonary resuscitation, prolonged cardiopulmonary bypass time, and total arch replacement were risk factors for in-hospital mortality. For patients who survived to discharge, the 5-year cumulative survival and freedom from aortic reoperation rates were 75.6% (95% confidence interval, 67.6%-83.6%) and 82.6% (95% confidence interval, 74.2%-91.1%), respectively. CONCLUSIONS: Preoperative shock in ATAAD is associated with a high risk of in-hospital mortality, particularly in patients who undergo cardiopulmonary resuscitation and complex aortic repair procedures with extended cardiopulmonary bypass. However, late outcomes are acceptable for patients who were stabilized through surgical treatment and survived to discharge.

Dynamic change of metabolic dysfunction-associated steatotic liver disease in patients with hepatitis C virus infection after achieving sustained virologic response with direct-acting antivirals.

BACKGROUND: Information on the dynamics of metabolic dysfunction-associated steatotic liver disease (MASLD) among hepatitis C virus patients achieving sustained virologic response (SVR12) with direct-acting antivirals (DAAs) is limited. METHODS: We enrolled 1512 eligible participants in this prospective study. MASLD was defined by a controlled attenuation parameter (CAP) of ≥248 dB/m utilizing vibration-controlled transient elastography in conjunction with presence of ≥1 cardiometabolic risk factor. The distribution of MASLD and the changes in CAP were evaluated before treatment and at SVR12. Forward stepwise logistic regression analyses were performed to determine factors significantly associated with the regression or emergence of MASLD. RESULTS: The prevalence of MASLD decreased from 45.0% before treatment to 36.1% at SVR12. Among 681 participants with MASLD before treatment, 144 (21%) exhibited MASLD regression at SVR12. Conversely, among 831 participants without MASLD before treatment, 9 (1.1%) developed MASLD at SVR12. Absence of type 2 diabetes (T2D) [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.13-2.65, p = 0.011], age > 50 years (OR: 1.73, 95% CI: 1.11-2.68, p = 0.015), and alanine transaminase (ALT) ≤ 2 times the upper limit of normal (ULN) (OR: 1.56; 95% CI: 1.03-2.37, p = 0.035) were associated with the regression of MASLD. Presence of T2D was associated with the emergence of MASLD (OR: 5.83, 95% CI: 1.51-22.56, p = 0.011). CONCLUSIONS: The prevalence of MASLD decreased after achieving SVR12 with DAAs. Patients with pre-existing T2D showed a diminished probability of MASLD regression and a heightened risk of MASLD emergence post-SVR12.

Association between Cholecystectomy and the Incidence of Pancreaticobiliary Cancer after Endoscopic Choledocholithiasis Management.

(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 (p < 0.0001), 2.11 (p = 0.0007), and 1.02 (p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.

[Distribution of Typical Resistant Bacteria and Resistance Genes in Source Water of the Middle and Lower Reaches of the Yellow River].

The Yellow River water of an urban area located in the middle and lower reaches of the Yellow River was taken as the research object， in which the seasonal and along-range distribution of total culturable bacteria， typical antibiotic resistant bacteria （amoxicillin resistant bacteria and sulfamethoxazole-resistant bacteria）， and their corresponding typical resistance genes ï¼»ß-lactam resistance gene （blaCTX-M） and sulfamamide resistance genes （sulI and sulⅡ）， as well as intⅠ1 were investigated. The results showed that the total culturable bacteria， ß-lactam-resistant bacteria and sulfonamide-resistant bacteria in the Yellow River Basin were significantly affected by temperature and human activities. The composition and quantity of their genera had obvious spatiotemporal distribution characteristics， in which Bacillus and Pseudomonas were dominant in the composition and number of bacteria. The abundance of resistance genes decreased with the decrease in temperature. The proportion of ß-lactam resistance genes in the total genes was higher than that of sulfanilamide genes， and sulI was the dominant gene in sulfanilamide genes. Correlation analysis showed that class Ⅰ integron played an important role in accelerating the spread of resistance genes. This study offers insight into the status quo of water resistance pollution in the Yellow River and provides theoretical support for the risk assessment of resistance genes in the middle and lower reaches of the Yellow River Basin.

Flexible nanohybrid substrates utilizing gold nanocubes/nano mica platelets with 3D lightning-rod effect for highly efficient bacterial biosensors based on surface-enhanced Raman scattering.

In this study, gold nanocubes (AuNCs) were quickly synthesized using the seed-mediated growth method and reduced onto the surface of two-dimensional (2D) delaminated nano mica platelets (NMPs), enabling the development of AuNCs/NMPs nanohybrids with a 3D lightning-rod effect. First, the growth-solution amount can be changed to easily adjust the AuNCs average-particle size within a range of 30-70 nm. The use of the cationic surfactant cetyltrimethylammonium chloride as a protective agent allowed the surface of AuNCs and nanohybrids to be positively charged. Positively charged nanohybrid surfaces presented a good adsorption effect for detecting molecules with negative charges on the surface. Additionally, the NMP surfaces were rich in ionic charges and provided a large specific surface area for stabilizing the growth of AuNCs. Delaminated AuNCs/NMPs nanohybrids can generate a 3D hotspot effect through self-assembly to enhance the Raman signal. Surface-enhanced Raman scattering (SERS) is highly sensitive in detecting adenine biomolecules. Its limit of detection (LOD) and Raman enhancement factor reached 10-9 M and 3.6 × 108, respectively. Excellent reproducibility was obtained owing to the relatively regular arrangement of AuNC particles, and the relative standard deviation (RSD) was 10.7%. Finally, the surface of NMPs was modified by adding the hydrophilic poly(oxyethylene)-diamine (POE2000) and amphiphilic PIB-POE-PIB copolymer at different weight ratios. The adjustment of the surface hydrophilicity and hydrophobicity of AuNCs/NMPs nanohybrids led to better adsorption and selectivity for bacteria. AuNCs/POE/NMPs and AuNCs/PIB-POE-PIB/NMPs were further applied to the SERS detection of hydrophilic Staphylococcus aureus and hydrophobic Escherichia coli, respectively. The SERS-detection results suggest that the LOD of hydrophilic Staphylococcus aureus and hydrophobic Escherichia coli reached 92 CFU mL-1 and 1.6 × 102 CFU mL-1, respectively. The AuNCs/POE/NMPs and AuNCs/PIB-POE-PIB/NMPs nanohybrids had different hydrophilic-hydrophobic affinities, which greatly improved the selectivity and sensitivity for detecting bacteria with different hydrophilicity and hydrophobicity. Therefore, fast, highly selective, and highly sensitive SERS biological-detection results were obtained.

Improving the Effects of Mulberry Leaves and Neochlorogenic Acid on Glucotoxicity-Induced Hepatic Steatosis in High Fat Diet Treated db/db Mice.

There are many complications of type 2 diabetes mellitus. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two complications related to the increased lipid accumulation in the liver. Previous studies have shown that mulberry leaf water extract (MLE) has the effect of lowering lipid levels in peripheral blood, inhibiting the expression of fatty acid synthase (FASN) and increasing the activity of liver antioxidant enzymes superoxide dismutase (SOD) and catalase. Our study aimed to investigate the role of MLE and its main component, neochlorogenic acid (nCGA), in reducing serum lipid profiles, decreasing lipid deposition in the liver, and improving steatohepatitis levels. We evaluated the antioxidant activity including glutathione (GSH), glutathione reductase (GRd), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD), and catalase was tested in mice fed with MLE and nCGA. The results showed a serum lipid profile, and fatty liver scores were significantly increased in the HFD group compared to the db/m and db mice groups, while liver antioxidant activity significantly decreased in the HFD group. When fed with HFD + MLE or nCGA, there was a significant improvement in serum lipid profiles, liver fatty deposition conditions, steatohepatitis levels, and liver antioxidant activity compared to the HFD group. Although MLE and nCGA do not directly affect the blood sugar level of db/db mice, they do regulate abnormalities in lipid metabolism. These results demonstrate the potential of MLE/nCGA as a treatment against glucotoxicity-induced diabetic fatty liver disease in animal models.

Acute type a aortic intramural hematoma complicated with preoperative hemopericardium: early and late surgical outcome analyses.

BACKGROUND: Acute type A aortic intramural hematoma (ATAIMH) is a variant of acute type A aortic dissection (ATAAD), exhibiting an increased risk of hemopericardium and cardiac tamponade. It can be life-threatening without emergency treatment. However, comprehensive studies of the clinical features and surgical outcomes of preoperative hemopericardium in patients with ATAIMH remain scarce. This retrospective study aims to investigate the clinical features and early and late outcomes of patients who underwent aortic repair surgery for ATAIMH complicated with preoperative hemopericardium. METHODS: We investigated 132 consecutive patients who underwent emergency ATAIMH repair at this institution between February 2007 and August 2020. These patients were dichotomized into the hemopericardium (n = 58; 43.9%) and non-hemopericardium groups (n = 74; 56.1%). We compared the clinical demographics, surgical information, postoperative complications, 5-year cumulative survival rates, and freedom from reoperation rates. Furthermore, multivariable logistic regression analysis was utilized to identify independent risk factors for patients who underwent re-exploration for bleeding. RESULTS: In the hemopericardium group, 36.2% of patients presented with cardiac tamponade before surgery. Moreover, the hemopericardium group showed higher rates of preoperative shock and endotracheal intubation and was associated with an elevated incidence of intractable perioperative bleeding, necessitating delayed sternal closure for hemostasis. The hemopericardium group exhibited higher blood transfusion volumes and rates of re-exploration for bleeding following surgery. However, the 5-year survival (59.5% vs. 75.0%; P = 0.077) and freedom from reoperation rates (93.3% vs. 85.5%; P = 0.416) were comparable between both groups. Multivariable analysis revealed that hemopericardium, cardiopulmonary bypass time, and delayed sternal closure were the risk factors for bleeding re-exploration. CONCLUSIONS: The presence of hemopericardium in patients with ATAIMH is associated with an elevated incidence of cardiac tamponade and unstable preoperative hemodynamics, which could lead to perioperative bleeding tendencies and high complication rates. However, patients of ATAIMH complicated with hemopericardium undergoing aggressive surgical intervention exhibited long-term surgical outcomes comparable to those without hemopericardium.