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Most traits are polygenic, and the contributing loci can be identified by genome-wide association studies. The genetic basis of adaptation (adaptive architecture) is, however, difficult to characterize. Here, we propose to study the adaptive architecture of traits by monitoring the evolution of their phenotypic variance during adaptation to a new environment in well-defined laboratory conditions. Extensive computer simulations show that the evolution of phenotypic variance in a replicated experimental evolution setting can distinguish between oligogenic and polygenic adaptive architectures. We compared gene expression variance in male Drosophila simulans before and after 100 generations of adaptation to a novel hot environment. The variance change in gene expression was indistinguishable for genes with and without a significant change in mean expression after 100 generations of evolution. We suggest that the majority of adaptive gene expression evolution can be explained by a polygenic architecture. We propose that tracking the evolution of phenotypic variance across generations can provide an approach to characterize the adaptive architecture. [ABSTRACT FROM AUTHOR]

Aims This study aimed to investigate the effectiveness of closed-loop stimulation (CLS) pacing compared with the traditional DDD mode in patients with chronotropic incompetence (CI) using bicycle-based cardiopulmonary exercise testing (CPET). Methods and results This single-centre, randomized crossover trial involved 40 patients with CI. Patients were randomized to receive either DDD-CLS or DDD mode pacing for 2 months, followed by a crossover to the alternative mode for an additional 2 months. Bicycling-based CPET was conducted at the 3- and 5-month follow-up visits to assess exercise capacity. Other cardiopulmonary exercise outcome measures and health-related quality of life (QoL) were also assessed. DDD-CLS mode pacing significantly improved exercise capacity, resulting in a peak oxygen uptake (14.8 ± 4.0 vs. 12.0 ± 3.6 mL/kg/min, P < 0.001) and oxygen uptake at the ventilatory threshold (10.0 ± 2.2 vs. 8.7 ± 1.8 mL/kg/min, P < 0.001) higher than those of the DDD mode. However, there were no significant differences in other cardiopulmonary exercise outcome measures such as ventilatory efficiency of carbon dioxide production slope, oxygen uptake efficiency slope, and end-tidal carbon dioxide between the two modes. Patients in the DDD-CLS group reported a better QoL, and 97.5% expressed a preference for the DDD-CLS mode. Conclusion DDD-CLS mode pacing demonstrated improved exercise capacity and QoL in patients with CI, highlighting its potential as an effective pacing strategy for this patient population. [ABSTRACT FROM AUTHOR]

Background and Objectives Falls among older adults are a significant health problem globally. Studies of multicomponent fall prevention programs in randomized controlled trials demonstrate effectiveness in reducing falls; however, the translation of research into the community remains challenging. Although there is an increasing interest to understand the factors contributing to implementation barriers, the dynamic relationships between factors are less well examined. Furthermore, evidence on implementation barriers from Asia is lacking as most of these studies originate from the West. As such, this study aims to engage stakeholders in uncovering the factors that facilitate or inhibit implementing community-based fall prevention programs in Singapore, with a focus on the interrelationship between those factors. Research Design and Methods Health care professionals familiar with fall prevention programs were invited to discuss the enablers and challenges to the implementation. This effort was facilitated using a systems modeling methodology of Group Model Building (GMB) to share ideas and create a common conceptual model of the challenges. The GMB employs various engagement techniques to draw on the experiences and perceptions of all stakeholders involved. Results This process led to the development of a Causal Loop Diagram (CLD), a qualitative conceptual model of the dynamic relationships between the barriers and facilitators of implementing fall prevention programs. Results from the CLD show that implementation is influenced by two main drivers: health care provider factors that influenced referrals, and patient factors that influenced referral acceptance and long-term adherence. Key leverage points for potential interventions were identified as well. Discussion and Implications The overall recommendation emphasized closer coordination and collaboration across providers to ensure sustainable and effective community-based fall prevention programs. This has to be supported by a national effort, involving a multidisciplinary stakeholder advisory group. These findings generated would be promising to guide future approaches to fall prevention. [ABSTRACT FROM AUTHOR]

Most organismal phenotypes have a polygenic basis, which enables adaptive phenotypic responses on ecological time scales. While adaptive phenotypic changes are highly parallel in replicate populations, this does not apply to the contributing loci. In particular for small populations, the same phenotypic shift can be fueled by different sets of alleles at alternative loci (genetic redundancy). Although this phenomenon is empirically well supported, the molecular basis of the genetic redundancy is not yet understood. To fill this gap, we compared the heterogeneity of the evolutionary transcriptomic and metabolomic response in ten Drosophila simulans populations which evolved parallel high-level phenotypic changes in a novel temperature environment but used different allelic combinations of alternative loci. We showed that the metabolome evolved more parallel than the transcriptome, confirming a hierarchical organization of molecular phenotypes. Different sets of genes responded in each evolved population but led to the enrichment of similar biological functions and a consistent metabolic profile. Since even the metabolomic response was still highly heterogeneous across evolved populations, we propose that selection may operate on pathways/networks. [ABSTRACT FROM AUTHOR]

Aims The prognostic implication of left ventricular (LV) torsion on ST-elevation myocardial infarction (STEMI) is unclear. Methods and results We analysed cardiovascular magnetic resonance (CMR) findings of 420 patients from a registry study (NCT03768453). These patients received CMR examination within 1 week after timely primary percutaneous coronary intervention. LV torsion and other CMR indexes were measured. Compared with healthy control subjects, STEMI significantly decreased patients' LV torsion (1.04 vs. 1.63°/cm, P < 0.001). During follow-up (median, 52 months), the reduction of LV torsion was greater in patients with than without composite major adverse cardiac and cerebrovascular events (MACCEs, 0.79 vs. 1.08°/cm, P < 0.001). The risk of MACCEs would increase to 1.125- or 1.092-fold, and the risk of 1-year LV remodelling would increase to 1.110- or 1.082-fold for every 0.1°/cm reduction in LV torsion after adjustment for clinical or CMR parameters respectively. When divided dichotomously, patients with LV torsion≤ 0.802°/cm had significantly higher risk of MACCEs (40.2 vs. 12.3%, P < 0.001) and more remarkable LV remodelling (46.1 vs. 11.9%, P < 0.001) than patients with better LV torsion. The addition of LV torsion to conventional prognostic factors such as the LV ejection fraction and infarction size led to a better risk classification model of patients for both MACCEs and LV remodelling. Finally, tobacco use, worse post-PCI flow, and greater microvascular obstruction size were presumptive risk factors for reduced LV torsion. Conclusion LV torsion measured by CMR is closely associated with the prognosis of STEMI and would be a promising indicator to improve patients' risk stratification. Clinical Trial Registration Clinicaltrials.gov, NCT03768453 [ABSTRACT FROM AUTHOR]

The article emphasizes the urgent need for worldwide cooperation to achieve net zero emissions (NZE) and combat climate change. It argues that China's involvement is crucial due to its significant manufacturing and research capabilities in areas such as lithium-ion batteries, solar cells, wind turbines, energy storage, and electric vehicles. The article highlights the interdependence of nations and the necessity for collaboration to overcome climate change. It calls on political leaders to prioritize NZE goals, implement free trade rules, establish expert international panels, and promote international cooperation to ensure the habitability of the planet for all. [Extracted from the article]

The aim of this study was to develop an efficient bioinoculant for amelioration of adverse effects from chilling stress (10°C), which are frequently occurred during rice seedling stage. Seed germination bioassay under chilling condition with rice (Oryza sativa L.) cv. Tainan 11 was performed to screen for plant growth-promoting (PGP) bacteria among 41 chilling-tolerant rice endophytes. And several agronomic traits were used to evaluate the effects of bacterial inoculation on rice seedling, which were experienced for 7-d chilling stress in walk-in growth chamber. The field trials were further used to verify the performance of potential PGP endophytes on rice growth. A total of three endophytes with multiple PGP traits were obtained. It was demonstrated that Pseudomonas sp. CC-LS37 inoculation led to 18% increase of maximal efficiency of Photosystem II (PSII) after 7-d chilling stress and 7% increase of chlorophyll a content, and 64% decline of malondialdehyde content in shoot after 10-d recovery at normal temperature in walk-in growth chamber. In field trial, biopriming of seeds with strain CC-LS37 caused rice plants to increase shoot chlorophyll soil plant analysis development values (by 2.9% and 2.5%, respectively) and tiller number (both by 61%) under natural climate and chilling stress during the end of tillering stage, afterward 30% more grain yield was achieved. In conclusion, strain CC-LS37 exerted its function in increase of tiller number of chilling stress-treated rice seedlings via improvement of photosynthetic characteristics, which in turn increases the rice grain yield. This study also proposed multiple indices used in the screening of potential endophytes for conferring chilling tolerance of rice plants. [ABSTRACT FROM AUTHOR]

Background Transcatheter therapy has become an alternative for functional mitral regurgitation (FMR) in patients at high surgical risk. However, the intervention of FMR in cardiac amyloidosis (CA) with transcatheter edge-to-edge repair (TEER) is controversial due to the potential risk of left atrial pressure (LAP) elevation. Case summary An 83-year-old woman with repeated heart failure (HF) and severe mitral regurgitation (MR) was referred to our centre for TEER. Pre-procedural transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) confirmed the degree of MR and a functional aetiology. A peculiar LAP increase in this patient occurred immediately after successful TEER clip implantation and her n -terminal prohormone of brain natriuretic peptide significantly increased post-operatively. The diagnosis of CA was suspected and was subsequently established through endomyocardial biopsy. Aggressive anti-HF therapy was initiated and the patient was discharged after her HF symptoms were relieved. At 6-month follow-up, the patient was still alive and no episode of acute HF was experienced. Discussion Severe functional MR in CA treated with TEER has the potential risk of increasing LAP. During the short-term follow-up, TEER appears beneficial for left heart function (reduction of MR) but harmful for right heart function (increase of LAP). CA patients with severe FMR should be carefully evaluated about the benefits and potential harm of TEER intervention. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research. [ABSTRACT FROM AUTHOR]

Objectives: Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). Methods: SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Results: Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. Conclusions: SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods. [ABSTRACT FROM AUTHOR]

The incidence of esophageal cancer has risen dramatically in the Western world. Although surgical resection of esophageal tumors is considered the cornerstone of curative approaches in localized esophageal cancer, approximately 40% of patients who undergo chemoradiation followed by surgery will experience a recurrence. Additionally, surgical resection is not a viable option for many patients with locally advanced unresectable disease, poor general condition or whose condition deteriorated following chemoradiation. Several investigators have, therefore, attempted to evaluate the outcomes of definitive chemoradiation in patients with localized or locally advanced esophageal cancer. The outcomes of concurrent chemoradiation remain a matter of debate given the heterogenous study design and treatment regimens used in recent trials. Understanding the clinical benefit of chemoradiation is essential prior to recommending it as an alternative to surgery. In our review, we present the most recent studies evaluating the role of chemoradiation to better define the clinical outcomes of patients with special attention to overall survival. [ABSTRACT FROM AUTHOR]

Cell wall invertase (CWI) and vacuolar invertase (VI) play multiple functions in plant growth. As well as depending on transcriptional and post-transcriptional regulation, there is growing evidence that CWI and VI are also subject to post-translational control by small inhibitory proteins. Despite the significance of this, genes encoding inhibitors, their molecular and biochemical properties, and their potential roles in regulating seed production have not been well documented in soybean (Glycine max). In this study, two invertase inhibitor isoforms, GmCIF1 and GmC/VIF2, were characterized to possess inhibitory activities in vitro via heterologous expression. Transcript analyses showed that they were predominantly expressed in developing seeds and in response to ABA. In accordance with this, surveys of primary targets showed subcellular localizations to the apoplast in tobacco epidermis after expressing YFPfusion constructs. Investigations using RNAi transgenic plants demonstrated marked elevations of CWI activities and improvements in seed weight in conjunction with higher accumulations of hexoses, starch, and protein in mature seeds. Further co-expression analyses of GmCIF1 with several putative CWI genes corroborated the notion that GmCIF1 modulation of CWI that affects seed weight is mainly contingent on post-translational mechanisms. Overall, the results suggest that post-translational elevation of CWI by silencing of GmCIF1 expression orchestrates the process of seed maturation through fine-tuning sucrose metabolism and sink strength. [ABSTRACT FROM AUTHOR]

Aims Hybridization usually leads to gene introgression between related species in hybrid zones, associated with complex patterns of morphological variation. Nevertheless, previous studies have tended to ignore the effects of geographic variation in hybridization rates on species taxonomy. This study aims to investigate the variation of morphological traits between two sympatric and taxonomically confused oak species, Quercus liaotungensis and Q. mongolica, and reveal the effects of hybridization rates on morphological traits and the taxonomic boundary. Methods We used seven microsatellite loci to evaluate species status and measured 15 morphological traits in 26 trees in the recent hybrid zone between Q. liaotungensis and Q. mongolica, and we characterized the differences between the two oak species and their hybrids for the investigated traits. Important Findings Molecular analyses indicated that 74% of 78 sampled maternal trees were hybrids between Q. liaotungensis and Q. mongolica although the observed morphological variation suggested that they had remained distinct species. Across all of the differentiated leaf and reproductive traits, the hybrids expressed patterns similar to Q. liaotungensis, which may suggest dominant expression of parental characters. These results are consistent with our expectation that hybrids will be difficult to distinguish from parental species in a recent hybrid zone. [ABSTRACT FROM AUTHOR]

Background. Cost and clinically significant adverse effects are the major limiting factors of interferon (IFN) use in therapy for chronic hepatitis B virus (HBV) infection. A clinical trial was conducted in China to study the efficiency and clinical relevance of low-dose regimen of IFN treatment for chronic HBV infection and to reveal factors predicting sustained combined response. Methods. During a randomized, open-label control study, hepatitis B e antigen (HBeAg)-positive patients with chronic HBV infection (n = 230) were assigned to receive pegylated IFN-α-2b (1.0 μg/kg) (n = 115) or IFN-α- 2b (3 MIU; n = 115) for a 24-week period. Sustained combined response was assessed 24 weeks after the completion of treatment. Results. The greater rate of HBeAg loss in the pegylated IFN-group (23%) was the only statistically significant difference between the 2 treatment arms observed at the end of follow-up. The results of the multivariate statistical analysis revealed that HBV genotype B and patient age (⩽25 years) were 2 independent factors associated with sustained combined response. A total of 40% of patients with HBV genotype B aged ⩽25-years achieved sustained combined response. Only 4 (1.7%) of 230 patients discontinued therapy because of clinically significant adverse effects. Conclusions. The choice of low-dose IFN regimen might be a relevant clinical option to reduce the cost and adverse effects of therapy for younger patients with chronic HBV infection and genotype B infection in countries where it is prevalent. [ABSTRACT FROM AUTHOR]

Abstract: The gene phaPAh, encoding the protein phasin that is associated with poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) granule of Aeromonas hydrophila 4AK4, was cloned and characterized. Recombinant strains harboring additional copies of the phasin gene (phaPAh) and the polyhydroxyalkanoate (PHA) synthase gene (phaCAh) accumulated PHBHHx copolyesters consisting of 21 mol% 3-hydroxyhexanoate (3HHx) as compared to 14 mol% 3HHx produced by wild type strain. The molecular weight of PHBHHx produced by the above recombinants was lower than that obtained from the wild type strain grown under similar conditions. Over-expression of phaPAh led to the production of more PHA granules but with reduced sizes. SDS–PAGE showed that PhaPAh was the predominant protein present in the PHBHHx granules. The RT-PCR results suggested that phasin PhaPAh, regulated phaCAh gene at the transcription level. Gene PhaPWe from Wautersia eutropha (formerly Ralstonia eutropha; encoding a 20kDa protein with low amino acid homology to the A. hydrophila 13kDa protein) cloned into A. hydrophila 4AK4 exhibited similar effects on PHBHHx production and PHBHHx composition. These data suggest that the phasins could represent a protein family possessing similar functions but different structures. [Copyright &y& Elsevier]

The visible spectrum of solar radiation is known to stimulate photoheterotrophic bacterial carbon metabolism. However, its impact on 'strictly' heterotrophic bacteria remains less explored. Here, we show that heterotrophic flavobacteria exhibit enhanced uptake and mineralization of dissolved organic carbon with increasing wavelengths of visible light, without employing any 'known' light-harvesting mechanisms. RNA sequencing identified blue light as a major constraint in the extracellular enzymatic hydrolysis of polymeric carbohydrates and acquisition of sugars, despite acting as a stimulus for inorganic carbon sequestration. In contrast, green–red and continuous full-spectrum lights activated diverse hydrolytic enzymes and sugar transporters, but obstructed inorganic carbon fixation. This 'metabolic switching' was apparent through limited nutrient uptake, suppressed light-sensitivity, oxidative stress response and promotion of inorganic carbon sequestration pathways under blue light. The visible light impact on metabolism may be of significant ecological relevance as it appears to promote cell-mediated mineralization of organic carbon in 'green-colored' chlorophyll-rich copiotrophic coastal seawater and inorganic carbon sequestration in 'blue-colored' oligotrophic open ocean. Thus, a novel regulatory role played by light on heterotrophic metabolism and a hidden potential of flavobacteria to sense and respond differentially to monochromatic lights influencing marine carbon cycling were unraveled. [ABSTRACT FROM AUTHOR]

Compares the conventional method and the impedance method for rapid detection of total counts of bacteria and fungi in bottled purified water. Indication that the detection rate for the two methods was 94.5 and 90.4 percent, respectively; Suggestion that impedance method is a rapid and accurate method.