Investigating the impact of various sorghum types on the key aroma compounds of Sichuan Xiaoqu Baijiu through application of the sensomics approach.

The aroma of Sichuan Xiaoqu Baijiu (SXB) greatly benefits from the use of sorghum as its primary brewing ingredient. Nevertheless, the impact of different sorghum variety on the primary aroma compounds of SXB has not been thoroughly investigated. Gas chromatography-mass spectrometry (GC-MS) in conjunction with headspace solid phase microextraction (HS-SPME) and liquid-liquid extraction (LLE) were employed in this investigation. Using 5 sorghum varieties as raw materials, five different types of SXB were analysed for their aroma compounds using GC-MS, GC-O, AEDA, aroma recombination, and aroma omission. Key aroma compounds of SXB were successfully identified as ethyl acetate, ethyl 2-methylbutyrate, isoamyl acetate, ethyl hexanoate, ethyl heptanoate, ethyl lactate, ethyl octanoate, ethyl decanoate, phenylethyl acetate, ethyl laurate, ethyl palmitate, isoamyl alcohol, phenylethanol, 1,1-diethoxyethane, 3-hydroxy-2- butanone, furfural, and glacial acetic acid. Glacial acetic acid, ethyl acetate, ethyl lactate, phenylethyl acetate, acetoin, phenylethanol, and ethyl caproate were found to be the seven major aroma compounds that had the biggest impact on the variations of the five SXB aroma properties, according to partial least squares regression (PLS-R) analysis. The collinear network analysis also revealed that the largest positive correlation weight was discovered between the protein and furfural content, tannin content and cereal-like aroma profile while the highest negative correlation weight was found between the moisture and acetoin content. This study is a valuable resource for understanding how raw materials control the directional regulation of the sensory quality of the SXB liquor body.

Spatial heterogeneity plays a vital role in shaping the structure and function of estuarine carbon-fixing bacterial communities.

Carbon-fixing bacterial communities are essential drivers of carbon fixation in estuarine ecosystems that critically affect the global carbon cycle. This study compared the abundances of the Calvin cycle functional genes cbbL and cbbM and Reductive tricarboxylic acid cycle gene aclB, as well as compared carbon-fixing bacterial community features in the two estuaries, predicted potential ecological functions of carbon-fixation bacteria, and analyzed their symbiosis strategies in two estuaries having different geographical distributions. Gammaproteobacteria was the dominant carbon-fixing bacterial community in the two estuaries. However, a higher number of Alphaproteobacteria were noted in the Liaohe Estuary, and a higher number of Betaproteobacteria were found in the Yalujiang Estuary. The carbon-fixing functional gene levels exhibited the order of aclB > cbbL > cbbM, and significant effects of Cu, Pb, and petroleum were observed (p < 0.05). Nitrogen-associated nutrient levels are major environmental factors that affect carbon-fixing bacterial community distribution patterns. Spatial factors significantly affected cbbL carbon-fixing functional bacterial community structure more than environmental factors. With the increase in offshore distance, the microbial-led processes of methylotrophy and nitrogen fixation gradually weakened, but a gradual strengthening of methanotrophy and nitrification was observed. Symbiotic network analysis of the microorganisms mediating these ecological processes revealed that the carbon-fixing bacterial community in these two estuaries had a non-random symbiotic pattern, and microbial communities from the same module were strongly linked among the carbon, nitrogen, and sulfur cycle. These findings could advance the understanding of carbon fixation in estuarine ecosystems.

Role of reimbursement and Physicians' awareness in the survival of sorafenib-eligible advanced hepatocellular carcinoma patients.

In 2008, sorafenib became the first approved systemic therapeutic agent for advanced HCC. Although its pharmacological efficacy has been established, reimbursement for such a new, high-cost drug, as well as physicians' awareness and prescription practice, likewise contribute to its clinical effectiveness. We therefore conducted a retrospective study using 38 sorafenib-eligible, advanced HCC patients when sorafenib was approved but not yet reimbursed as a control and 216 patients during the reimbursed era. Study group showed longer survival at 8.2 months versus the control's 4.9 months (p = 0.0063 hazard ratio: 0.612 [0.431 ~ 0.868], p = 0.0059). Among the 42 (19.4%) patients who survived more than 2 years, 50% had tumor rupture, and all 32 patients with portal vein tumor thrombus and/or extrahepatic metastasis received sorafenib (p = 0.003). Furthermore, during their first 2 years of HCC management, sorafenib had been given in 29.1% of the treatment courses among survivors between 2 and 5 years while it was prescribed in 55.8% among the more than 5 years survivor group (p < 0.001). In conclusion, survival of sorafenib-eligible HCC patients significantly improved after reimbursement. Patients who underwent longer sorafenib treatment had a survival advantage, except for those with tumor rupture. Reimbursement and awareness of prescriptions for a newly introduced medication therefore improve clinical effectiveness.

Accurately Modulating Binuclear Metal Nodes of Metal-Organic Frameworks for Oxygen Evolution.

The accurate manipulation of the species and locations of catalytic centers is crucial for regulating the catalytic activity of catalysts, which is essential for their efficient design and development. Metal-organic frameworks (MOFs) with coordinated metal sites are ideal materials for investigating the origin of catalytic activity. In this study, we present a Ni2-MOF featuring novel Ni-based binuclear nodes with open metal sites (OMSs) and saturated metal sites (SMSs). The nickel was replaced by iron to obtain Ni1Fe1-MOF. In the electrocatalytic oxygen evolution reaction, Ni1Fe1-MOF exhibited an overpotential and Tafel slope of 370 mV@10 mA cm-2 and 87.06 mV dec-1, respectively, which were higher than those of Ni2-MOF (283 mV@10 mA cm-2 and 39.59 mV dec-1, respectively), demonstrating the superior performance of Ni1Fe1-MOF. Furthermore, theoretical calculations revealed that iron as an SMS may effectively regulate the electronic structure of the nickel catalytic center to reduce the free energy barrier ΔG*OH of the rate-determining step.

Lactiplantibacillus sp. G6 isolated from goose intestine as starter culture for degrading nitrite and improving quality in Chinese pickle fermentation.

Animal intestines is considered as a source of lactic acid bacteria (LAB) that have potential to decrease the nitrite level during fermentation of food such as pickles. It was hypothesized that optimized level of LAB has a high capacity to degrade nitrite during Chinese pickle fermentation and benefit a higher acceptability of the Chinese pickle product. This study aims to investigate the performance of a goose intestine-isolated LAB strain G6 under the species Lactiplantibacillus plantarum as a starter culture of Chinese pickles. The results showed that Lactiplantibacillus sp. G6 had a nitrite degradation rate close to 100% under the MRS broth condition of 25 °C, 2% inoculum volume and pH at 5. As a starter culture for Chinese pickle, this strain was able to achieve a higher LABs amount, lower nitrite residue after fermentation, compared with the group without the starter, which implicates its feasibility of applying on fermented food for reducing nitrite level. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01433-8.

Hollow microsphere probes formed by hollow core optical fiber discharging for monitoring gas pressure and temperature.

A hollow core fiber (HCF) is spliced with a single-mode fiber, and then, the end face of the HCF is etched to form a microsphere interferometer for measuring gas pressure and environmental temperature. The total length of each microsphere is less than 200 µm. We fabricated two such structures and used femtosecond laser pulses to drill micro-holes on the HCF walls of both structures. One of the structures is directly used to measure air pressure, achieving a sensitivity of up to 2.857 nm/MPa while being almost insensitive to temperature. This structure is capable of assessing pressure down to 3.4 kPa within the range of 0-0.5 MPa. Another structure is filled with thermally sensitive material dimethyl silicone oil through a micro-hole, and then, it is sealed with AB adhesive to form a harmonic Vernier effect temperature sensor, with a sensitivity of up to -5.16 nm/°C. This structure is capable of assessing temperature down to 0.38 °C within the range of 30-60 °C. Additionally, the sensors have good repeatability and stability and compact structure and simple manufacturing and can be used as a sensing probe for monitoring gas pressure and temperature under extreme environments.

Spatial distribution characteristics and interaction effects of DOM and microbial communities in kelp cultivation areas.

The influence of macroalgae cultivation on aquaculture carbon sinks is significant, with microbial carbon (C) pumps contributing to a stable inert dissolved carbon pool in this context. Concurrently, dissolved organic matter (DOM) exchange at the marine sediment-water interface profoundly affects global ecosystem element cycling. However, the interactions between DOM and bacterial communities at the sediment-water interface in kelp cultivation areas, especially regarding microbial function prediction, have not been fully explored. This study analyzed the DOM characteristics, environmental factors, and bacterial community structure in the Tahewan kelp--Saccharina japonica cultivated area and compared them with those in non-cultivated areas. The results indicated significantly higher dissolved organic carbon (DOC) concentrations in the kelp culture area, particularly in surface seawater and overlying water. The dominant bacterial phyla in both regions included Pseudomonadota, Actinomycetota, and Bacteroidota in both regions, while Desulfobacterota was more prevalent in the sediment environment of the cultivated region. Parallel factor analysis (EEM-PARAFAC) was used to identify DOM components, among which component C2 (a microbial humic-like substance DOM) was highly resistant to microbial degradation. We infer that C2 has similar properties to recalcitrant dissolved organic matter (RDOM). Analysis of the predicted functional genes based on 16S rRNA gene data showed that methanol oxidation, methylotrophy, and methanotrophy were significant in the bottom seawater of the cultivation area. The carbon (C), nitrogen (N), and sulfur (S) cycle functional genes in the sediment environment of the kelp cultivation area were more active than those in other areas, especially in which sulfate reduction and denitrification were the two main processes. Furthermore, a DOM priming effect was identified in the cultivated sediment environment, where kelp-released labile dissolved organic matter (LDOM) stimulates rapid degradation of the original RDOM, potentially enhancing C sequestration.

Age-dependent genes in adipose stem and precursor cells affect regulation of fat cell differentiation and link aging to obesity via cellular and genetic interactions.

BACKGROUND: Age and obesity are dominant risk factors for several common cardiometabolic disorders, and both are known to impair adipose tissue function. However, the underlying cellular and genetic factors linking aging and obesity on adipose tissue function have remained elusive. Adipose stem and precursor cells (ASPCs) are an understudied, yet crucial adipose cell type due to their deterministic adipocyte differentiation potential, which impacts the capacity to store fat in a metabolically healthy manner. METHODS: We integrated subcutaneous adipose tissue (SAT) bulk (n=435) and large single-nucleus RNA sequencing (n=105) data with the UK Biobank (UKB) (n=391,701) data to study age-obesity interactions originating from ASPCs by performing cell-type decomposition, differential expression testing, cell-cell communication analyses, and construction of polygenic risk scores for body mass index (BMI). RESULTS: We found that the SAT ASPC proportions significantly decrease with age in an obesity-dependent way consistently in two independent cohorts, both showing that the age dependency of ASPC proportions is abolished by obesity. We further identified 76 genes (72 SAT ASPC marker genes and 4 transcription factors regulating ASPC marker genes) that are differentially expressed by age in SAT and functionally enriched for developmental processes and adipocyte differentiation (i.e., adipogenesis). The 76 age-perturbed ASPC genes include multiple negative regulators of adipogenesis, such as RORA, SMAD3, TWIST2, and ZNF521, form tight clusters of longitudinally co-expressed genes during human adipogenesis, and show age-based differences in cellular interactions between ASPCs and adipose cell types. Finally, our genetic data demonstrate that cis-regional variants of these genes interact with age as predictors of BMI in an obesity-dependent way in the large UKB, while no such gene-age interaction on BMI is observed with non-age-dependent ASPC marker genes, thus independently confirming our cellular ASPC results at the biobank level. CONCLUSIONS: Overall, we discover that obesity prematurely induces a decrease in ASPC proportions and identify 76 developmentally important ASPC genes that implicate altered negative regulation of fat cell differentiation as a mechanism for aging and directly link aging to obesity via significant cellular and genetic interactions.

PcENO3 interacts with patchoulol synthase to positively affect the enzymatic activity and patchoulol biosynthesis in Pogostemon cablin.

Patchouli alcohol, a significant bioactive component of the herbal plant Pogostemon cablin, has considerable medicinal and commercial potential. Several genes and transcription factors involved in the biosynthesis pathway of patchouli alcohol have been identified. However, so far, regulatory factors directly interacting with patchouli synthase (PTS) have not been reported. This study was conducted to analyze the interaction between PcENO3 and PcPTS to explore the molecular regulation effect of PcENO3 on patchouli alcohol biosynthesis. PcENO3, a homologous protein of Arabidopsis ENO3 belonging to the enolase family, was identified and characterized. Subcellular localization experiments in Arabidopsis protoplast cells indicated that the PcENO3 protein was localized in both the cytoplasm and nucleus. The physical interaction between PcENO3 and PcPTS was confirmed through yeast two-hybrid (Y2H), GST pull-down, and bimolecular fluorescence complementation assays. Furthermore, the Y2H assay demonstrated that PcENO3 could also interact with JAZ proteins in the JA pathway. Enzymatic assays showed that the interaction with PcENO3 increased the catalytic activity of patchoulol synthase. Additionally, suppression of PcENO3 expression with VIGS (virus-induced gene silencing) decreased patchouli alcohol content compared to the control. These findings suggest that PcENO3 interacts with patchoulol synthase and modulates patchoulol biosynthesis by enhancing the enzymatic activity of PcPTS.

Magnetic field and gas pressure sensor based on Mach-Zehnder interferometer with micro-groove fabricated by femtosecond laser pulse.

A microgroove type Mach-Zehnder interferometer (MZI) for gas pressure and magnetic field measurements was prepared using a femtosecond laser pulse in a single mode fiber. Due to the interference light passing through the microgroove, changing the refractive index (RI) of the medium in the microgroove will change the optical path difference between the two channels, leading to significant drift of the MZI transmission spectrum, thus achieving the measurement of environmental parameters. When the gas pressure inside the microgroove changes, the RI of the air changes, achieving the measurement of environmental gas pressure. When the microgroove is filled with magnetic fluid, changes in the environmental magnetic field will cause changes in the RI of the magnetic fluid, thus achieving measurement of the magnetic field. The experimental results show that the gas pressure sensitivity of the sensor is -5.03 nm/MPa, and the temperature cross-sensitivity is only 1.31 kPa/°C. This sensor achieves a magnetic field sensitivity of -0.3505 nm/mT in the magnetic field range of 6.4-13.6 mT. The sensor is small in size and easy to manufacture, making it a good choice for measuring air pressure and magnetic field.

Compact highly sensitive Fabry-Perot temperature and gas pressure sensing probe fabricated by a femtosecond laser and PDMS.

A high sensitivity optical fiber temperature and gas pressure sensor with integrated micro-cavity is proposed. First, a single-mode optical fiber (SMF) is spliced with a section of capillary, and then the sensitive material polydimethylsiloxane (PDMS) is filled into the capillary to form a Fabry-Perot interferometer (FPI). Finally, a femtosecond laser is used to ablate the fiber core of the SMF to form the third reflecting surface, constituting two cascaded FPIs. When two FPIs have a similar free spectral range, a Vernier effect is produced. The temperature and gas pressure sensitivity of the sensor reached 14.41 nm/°C and 113.82 nm/MPa, respectively, after using the sensitive material and Vernier effect double sensitization technology. In addition, a fiber Bragg grating is cascaded with the sensor, which can realize the simultaneous measurement of temperature and gas pressure and eliminate cross-sensitivity.

Retinol-binding protein-hijacking nanopolyplex delivering siRNA to cytoplasm of hepatic stellate cell for liver fibrosis alleviation.

Activated hepatic stellate cell (aHSC) is mainly responsible for deposition of extracellular collagen matrix that causes liver fibrosis. Although several siRNAs adequately inhibited HSC activation in vitro, they were demonstrated poor RNAi efficiency in vivo. Developing HSC-targeting and cytoplasmic delivery nanocarrier is highly essential to acquire a desirable siRNA therapeutic index for anti-liver fibrosis. Here, we developed a unique crosslinking nanopolyplex (called T-C-siRNA) modified by vitamin A (VA) with the well-designed natures, including the negative charge, retinol-binding protein (RBP) hijacking, and cytoplasmic siRNA release in response to ROS and cis diol molecules. The nanopolyplex was given a yolk-shell-like shape, camouflage ability in blood, and HSC-targeting capability by hijacking the endogenous ligand RBP via surface VA. PDGFR-ß siRNA (siPDGFR-ß) supplied via T-C-siPDGFR-ß nanopolyplex dramatically reduced HSC activation and its production of pro-fibrogenic proteins in vitro and in vivo. Furthermore, T-C-siPDGFR-ß nanopolyplex effectively alleviated CCl4-induced liver injury, decreased hepatic collagen sediment, and recovered liver function in mice. This study provides a sophisticated method for HSC-targeting cytoplasmic RNA delivery using endogenous ligand hijacking and dual sensitivity of ROS and cis diol compounds.

Association of Kinase-Insert-Domain-Containing Receptor Polymorphisms with Glioma Susceptibility in a Chinese Population: A Hospital-Based Case-Control Study.

Background: Gliomas are the most common malignant tumors of the central nervous system. However, the inherited genetic variation in gliomas is presently unclear. Therefore, this study investigated the association of the rs2071559 and rs2239702 gene polymorphisms with glioma susceptibility in Chinese patients. Methods: In this study, a case-control approach was used to compare and analyze whether two genes, rs2071559 and rs2239702, were associated with the risk of glioma formation. Results: The cases and controls were matched for sex, smoking status, and family history of cancer using single nucleotide polymorphisms. Specific rs2071559 and rs2239702 alleles were found much more frequently in the glioma group than in the control group (P < 0.001 and P = 0.014, respectively). Conclusions: These findings suggest that specific rs2071559 and rs2239702 polymorphisms are associated with a higher risk of glioma development; the risk allele is C in rs2071559 or A in rs2239702. Moreover, the kinase-insert-domain-containing receptor may act as a suppressor of tumor progression.

Contactin-6-deficient male mice exhibit the abnormal function of the accessory olfactory system and impaired reproductive behavior.

INTRODUCTION: Contactin-6 (CNTN6), also known as NB-3, is a neural recognition molecule and a member of the contactin subgroup of the immunoglobulin superfamily. Gene encoding CNTN6 is expressed in many regions of the neural system, including the accessory olfactory bulb (AOB) in mice. We aim to determine the effect of CNTN6 deficiency on the function of the accessory olfactory system (AOS). METHODS: We examined the effect of CNTN6 deficiency on the reproductive behavior of male mice through behavioral experiments such as urine sniffing and mate preference tests. Staining and electron microscopy were used to observe the gross structure and the circuitry activity of the AOS. RESULTS: Cntn6 is highly expressed in the vomeronasal organ (VNO) and the AOB, and sparsely expressed in the medial amygdala (MeA) and the medial preoptic area (MPOA), which receive direct and/or indirect projections from the AOB. Behavioral tests to examine reproductive function in mice, which is mostly controlled by the AOS, revealed that Cntn6-/- adult male mice showed less interest and reduced mating attempts toward estrous female mice in comparison with their Cntn6+/+ littermates. Although Cntn6-/- adult male mice displayed no obvious changes in the gross structure of the VNO or AOB, we observed the increased activation of granule cells in the AOB and the lower activation of neurons in the MeA and the MPOA as compared with Cntn6+/+ adult male mice. Moreover, there were an increased number of synapses between mitral cells and granule cells in the AOB of Cntn6-/- adult male mice as compared with wild-type controls. CONCLUSION: These results indicate that CNTN6 deficiency affects the reproductive behavior of male mice, suggesting that CNTN6 participated in normal function of the AOS and its ablation was involved in synapse formation between mitral and granule cells in the AOB, rather than affecting the gross structure of the AOS.

ThermalProGAN: A sequence-based thermally stable protein generator trained using unpaired data.

MOTIVATION: The synthesis of proteins with novel desired properties is challenging but sought after by the industry and academia. The dominating approach is based on trial-and-error inducing point mutations, assisted by structural information or predictive models built with paired data that are difficult to collect. This study proposes a sequence-based unpaired-sample of novel protein inventor (SUNI) to build ThermalProGAN for generating thermally stable proteins based on sequence information. RESULTS: The ThermalProGAN can strongly mutate the input sequence with a median number of 32 residues. A known normal protein, 1RG0, was used to generate a thermally stable form by mutating 51 residues. After superimposing the two structures, high similarity is shown, indicating that the basic function would be conserved. Eighty four molecular dynamics simulation results of 1RG0 and the COVID-19 vaccine candidates with a total simulation time of 840[Formula: see text]ns indicate that the thermal stability increased. CONCLUSION: This proof of concept demonstrated that transfer of a desired protein property from one set of proteins is feasible. Availability and implementation: The source code of ThermalProGAN can be freely accessed at https://github.com/markliou/ThermalProGAN/ with an MIT license. The website is https://thermalprogan.markliou.tw:433. Supplementary information: Supplementary data are available on Github.

Above-Standard Survival of Hepatocellular Carcinoma as the Final Outcome of Comprehensive Hepatology Care Programs in a Remote HCV-Endemic Area.

Early detection and prompt linkage to care are critical for hepatocellular carcinoma (HCC) care. Chang Gung Memorial Hospital (CGMH) Yunlin branch, a local hospital in a rural area, undertakes health checkup programs in addition to its routine clinical service. Patients with HCC are referred to CGMH Chiayi branch, a tertiary referral hospital, for treatment. This study enrolled 77 consecutive patients with newly diagnosed HCCs between 2017 and 2022, with a mean age of 65.7 ± 11.1 years. The screening group included HCC patients detected through health checkups, and those detected by routine clinical service served as the control group. Compared to the 24 patients in the control group, the 53 patients in the screening group had more cases with early stage cancer (Barcelona Clinic Liver Cancer or BCLC stage 0 + A 86.8% vs. 62.5%, p = 0.028), better liver reserve (albumin-bilirubin or ALBI grade I 77.3% vs. 50%, p = 0.031) and more prolonged survival (p = 0.036). The median survival rates of the 77 patients were >5 years, 3.3 years, and 0.5 years in the BCLC stages 0 + A, B, and C, respectively, which were above the expectations of the BCLC guideline 2022 for stages 0, A, and B. This study provides a model of HCC screening and referral to high-quality care in remote viral-hepatitis-endemic areas.

Fine-Tuned Polymer Nanoassembly for Codelivery of Chemotherapeutic Drug and siRNA.

Successful clinical application of siRNA to liver-associated diseases reinvigorates the RNAi therapeutics and delivery vectors, especially for anticancer combination therapy. Fine tuning of copolymer-based assembly configuration is highly important for a desirable synergistic cancer cell-killing effect via the codelivery of chemotherapeutic drug and siRNA. Herein, an amphiphilic triblock copolymer methoxyl poly(ethylene glycol)-block-poly(L-lysine)-block-poly(2-(diisopropyl amino)ethyl methacrylate) (abbreviated as mPEG-PLys-PDPA or PLD) consisting of a hydrophilic diblock mPEG-PLys and a hydrophobic block PDPA is synthesized. Three distinct assemblies (i.e., nanosized micelle, nanosized polymersome, and microparticle) are acquired, along with the increase in PDPA block length. Furthermore, the as-obtained polymersome can efficiently codeliver doxorubicin hydrochloride (DOX) as a hydrophilic chemotherapeutic model and siRNA against ADP-ribosylation factor 6 (siArf6) as an siRNA model into cancer cell via lysosomal pH-triggered payload release. PC-3 prostate cell is synergistically killed by the DOX- and siArf6-coloading polymersome (namely PLD@DOX/siArf6). PLD@DOX/siArf6 may serve as a robust nanomedicine for anticancer therapy.

High sensitivity temperature sensor based on enhanced Vernier effect through two parallel Fabry-Perot cavities.

In this paper, an enhanced Vernier effect temperature sensor based on two parallel Fabry-Perot interferometers (FPIs) is proposed and demonstrated experimentally. Among them, F P I 1 is composed of a single-mode fiber (SMF), a quartz capillary, and AB glue filled in the capillary. F P I 2 is formed by filling a capillary with polyimide (PI) solution and inserting two-segment SMF from both sides of the capillary. Since AB glue and PI have good thermal sensitivity, F P I 1 and F P I 2 are highly sensitive to temperature. Due to their different structures, the temperature sensitivity of F P I 1 is negative, and that of F P I 2 is positive. When F P I 1 and F P I 2 with similar free spectral range are connected in parallel, they will act as reference cavities for each other, resulting in an enhanced Vernier effect, which enlarges the sensitivity of the sensor more. In the temperature range of 40°C-58°C, the temperature sensitivity of the sensor is as high as -13.09n m/∘ C, and the fitting coefficient is 0.9974. The experimental results show that in the enhanced Vernier effect sensor structure, only two FPIs with opposite temperature sensitivity are required, which does not increase the difficulty and cost of sensor manufacturing. In addition, the sensor has good stability and repeatability.

Essen Stroke Risk Score Predicts Clinical Outcomes in Heart Failure Patients with Preserved Ejection Fraction: Evidence from the TOPCAT trial.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with increased risks of stroke and other adverse outcomes. AIMS: This study sought to determine whether the Essen Stroke Risk Score (ESRS) could predict the risks of adjudicated clinical outcomes in patients with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. METHODS: We evaluated associations of baseline ESRS with clinical outcomes by using the Cox proportional hazard model with competing risk regression. The diagnostic accuracy of the ESRS was assessed using the C-index and calibration data. RESULTS: Of 3,441 HFpEF patients with a mean follow-up of 3.3 years, the risk of stroke ranged from 0.32% per year at an ESRS of 1 to 2 points to 1.71% per year at a score of ≥6 points. Each point increase in ESRS was associated with increased risks of primary composite outcome (hazard ratios [HRs] = 1.31; 95% confidence intervals [CIs]: 1.23-1.40; C-index = 0.68), stroke (HR = 1.33 [95% CI: 1.16-1.53]; C-index = 0.68), myocardial infarction (HR = 1.60 [95% CI: 1.40-1.83]; C-index = 0.75), HF hospitalization (HR = 1.30 [95% CI: 1.20-1.41]; C-index = 0.71), any hospitalization (HR = 1.20, 95% CI: 1.15-1.26; C-index = 0.68), cardiovascular death (HR = 1.32 [95% CI: 1.20-1.44]; C-index = 0.68), and all-cause death (HR = 1.37, [95% CI: 1.28-1.48]; C-index = 0.68). The calibration curves showed that the ESRS had a better agreement between predicted and observed stroke risks compared with the R2CHADS2, CHADS2, or CHA2DS2-VASC stroke scores. CONCLUSION: The ESRS had modest discriminatory abilities for predicting stroke as well as other adverse outcomes including myocardial infarction, hospitalization, and death in HFpEF patients. ESRS might have better calibration performance than R2CHADS2, CHADS2, or CHA2DS2-VASC in HFpEF at high risk for stroke. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00094302.

The effect of Lactobacillus with prebiotics on KPC-2-producing Klebsiella pneumoniae.

Objectives: This study investigated the inhibitory effect of Lactobacillus spp. with prebiotics against Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing Klebsiella pneumoniae using both in vitro experiments and animal models. Methods: Thirty-three Lactobacillus spp. strains were confirmed by 16S rDNA sequencing, and four different PFGE genotyped KPC-2-producing K. pneumoniae strains were selected for investigation. In vitro studies, including broth microdilution assays, changes in pH values in lactobacilli cultures with different prebiotics, time-kill tests of Lactobacillus spp. against KPC-2-producing K. pneumoniae and further in vivo Lactobacillus alone or in combination with prebiotics against KPC-2-producing K. pneumoniae in an animal model, were performed. Results: The lower pH value of the cell-free supernatant was associated with a lower minimal inhibitory percentage of the Lactobacillus strain against KPC-2-producing K. pneumoniae. Furthermore, lactulose/isomalto-oligosaccharide/inulin and fructo-oligosaccharide can enhance the inhibitory effect of all 107 CFU/ml Lactobacillus strains against KPC001. Three Lactobacillus strains (LYC1154, LYC1322, and LYC1511) that could be persistently detected in the stool were tested for their ability to reduce the amount of KPC001 in the feces individually or in combination. A significantly better effect in reducing the amount of KPC001 was observed for the combination of three different Lactobacillus species than for each of them alone. Furthermore, their inhibitory effect was enhanced after adding lactulose or isomalto-oligosaccharide (both p < 0.05). Conclusion: This study demonstrates the inhibitory effect of probiotic Lactobacillus, including LYC1154, LYC1322, and LYC1511, with prebiotics such as lactulose or isomalto-oligosaccharide against the colonization of KPC-2-producing K. pneumoniae.