Indole-3-Propionic Acid Protects Against Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common but poorly understood form of heart failure, characterized by impaired diastolic function. It is highly heterogeneous with multiple comorbidities, including obesity and diabetes, making human studies difficult. METHODS: Metabolomic analyses in a mouse model of HFpEF showed that levels of indole-3-propionic acid (IPA), a metabolite produced by gut bacteria from tryptophan, were reduced in the plasma and heart tissue of HFpEF mice as compared with controls. We then examined the role of IPA in mouse models of HFpEF as well as 2 human HFpEF cohorts. RESULTS: The protective role and therapeutic effects of IPA were confirmed in mouse models of HFpEF using IPA dietary supplementation. IPA attenuated diastolic dysfunction, metabolic remodeling, oxidative stress, inflammation, gut microbiota dysbiosis, and intestinal epithelial barrier damage. In the heart, IPA suppressed the expression of NNMT (nicotinamide N-methyl transferase), restored nicotinamide, NAD+/NADH, and SIRT3 (sirtuin 3) levels. IPA mediates the protective effects on diastolic dysfunction, at least in part, by promoting the expression of SIRT3. SIRT3 regulation was mediated by IPA binding to the aryl hydrocarbon receptor, as Sirt3 knockdown diminished the effects of IPA on diastolic dysfunction in vivo. The role of the nicotinamide adenine dinucleotide circuit in HFpEF was further confirmed by nicotinamide supplementation, Nnmt knockdown, and Nnmt overexpression in vivo. IPA levels were significantly reduced in patients with HFpEF in 2 independent human cohorts, consistent with a protective function in humans, as well as mice. CONCLUSIONS: Our findings reveal that IPA protects against diastolic dysfunction in HFpEF by enhancing the nicotinamide adenine dinucleotide salvage pathway, suggesting the possibility of therapeutic management by either altering the gut microbiome composition or supplementing the diet with IPA.

Investigation on screening, identification, and fermentation characteristics of Yunnan olive in the fermented liquid utilizing five strains of Saccharomyces cerevisiae.

Refined indigenous Saccharomyces cerevisiae can enhance refinement, sophistication, and subtlety of fruit wines by showcasing exceptional regional characteristics. In order to identify exceptional indigenous S. cerevisiae strains from Yunnan olive, this study isolated 60 yeast strains from wild Yunnan olive fermentation mash. The five S. cerevisiae strains were subjected to morphological and molecular biological identification, followed by evaluation of their fermentation performance, ethanol production capacity, ester production capacity, H2S production capacity, killing capacity, and tolerance. Strains LJM-4, LJM-10, and LJM-26 exhibited robust tolerance to 6% ethanol volume fraction, pH 2.8, sucrose concentration of 400 g/L, SO2 concentration of 0.3 g/L, glucose concentration of 400 g/L at both 40 °C and 15 °C. Additionally, strain LJM-10 demonstrated a faster fermentation rate compared to the other strains. Among the tested S. cerevisiae strains evaluated in this study for olive wine fermentation process in Yunnan region; strain LJM-10 displayed superior abilities in terms of ester and ethanol production while exhibiting the lowest H2S production levels. These findings suggest that strain LJM-10 holds great potential as an excellent candidate for optimizing fruit wine S. cerevisiae fermentation processes in Yunnan olive fruit wine.

Isolation, identification, and tolerance analysis of yeast during the natural fermentation process of Sidamo coffee beans.

Yeast, which plays a pivotal role in the brewing, food, and medical industries, exhibits a close relationship with human beings. In this study, we isolated and purified 60 yeast strains from the natural fermentation broth of Sidamo coffee beans to screen for indigenous beneficial yeasts. Among them, 25 strains were obtained through morphological characterization on nutritional agar medium from Wallerstein Laboratory (WL), with molecular biology identifying Saccharomyces cerevisiae strain YBB-47 and the remaining 24 yeast strains identified as Pichia kudriavzevii. We investigated the fermentation performance, alcohol tolerance, SO2 tolerance, pH tolerance, sugar tolerance, temperature tolerance, ester production capacity, ethanol production capacity, H2S production capacity, and other brewing characteristics of YBB-33 and YBB-47. The results demonstrated that both strains could tolerate up to 3% alcohol by volume at a high sucrose mass concentration (400 g/L) under elevated temperature conditions (40 ℃), while also exhibiting a remarkable ability to withstand an SO2 mass concentration of 300 g/L at pH 3.2. Moreover, S. cerevisiae YBB-47 displayed a rapid gas production rate and strong ethanol productivity. whereas P. kudriavzevii YBB-33 exhibited excellent alcohol tolerance. Furthermore, this systematic classification and characterization of coffee bean yeast strains from the Sidamo region can potentially uncover additional yeasts that offer high-quality resources for industrial-scale coffee bean production.

Identification of the interchromophore interaction in the electronic absorption and circular dichroism spectra of bis-phenanthrenes.

We characterize the low-lying excited electronic states of a series of bis-phenanthrenes using our newly developed diabatic scheme called the fragment particle-hole density (FPHD) method and calculate both the electronic absorption and circular dichroism (ECD) spectra using the time-dependent density functional theory (TDDFT) and the FPHD-based exciton model which couples intrachromophore local excitations (LEs) and the interchromophore charge-transfer excitations (CTEs). TDDFT treats each bis-phenanthrene as a single molecule while the mixed LE-CTE exciton model partitions the molecule into two phenanthrene-based aromatic moieties, and then applies the electronic coupling between the various quasi-diabatic states to cover the interactions. It is found that TDDFT and the mixed LE-CTE model reproduce all experimentally observed trends in the spectral profiles, and the hybridization between LE and CTE states is displayed differently in absorption and ECD spectral intensities, as it usually decreases the absorption maxima and affects the positive/negative extrema of the ECD irregularly. By comparing the results yielded by the LE-CTE model with and without the LE-CTE coupling, we identify the contribution of CTE on the main dipole-allowed transitions.

Phonon-mediated ultrafast energy- and momentum-resolved hole dynamics in monolayer black phosphorus.

The electron-phonon scattering plays a crucial role in determining the electronic, transport, optical, and thermal properties of materials. Here, we employ a non-Markovian stochastic Schrödinger equation (NMSSE) in momentum space, together with ab initio calculations for energy bands and electron-phonon interactions, to reveal the phonon-mediated ultrafast hole relaxation dynamics in the valence bands of monolayer black phosphorus. Our numerical simulations show that the hole can initially remain in the high-energy valence bands for more than 100 fs due to the weak interband scatterings, and its energy relaxation follows single-exponential decay toward the valence band maximum after scattering into low-energy valence bands. The total relaxation time of holes is much longer than that of electrons in the conduction band. This suggests that harnessing the excess energy of holes may be more effective than that of electrons. Compared to the semiclassical Boltzmann equation based on a hopping model, the NMSSE highlights the persistence of quantum coherence for a long time, which significantly impacts the relaxation dynamics. These findings complement the understanding of hot carrier relaxation dynamics in two-dimensional materials and may offer novel insights into harnessing hole energy in photocatalysis.

Psychromicrobium Xiongbiense sp. nov., an Actinobacterium Isolated from Forest Soil.

A novel Gram-stain-positive, oval-shaped, and non-flagellated bacterial strain YIM S02556T was isolated from forest soil in Xiongbi Town, Shizong County, Qujing City, Yunnan Province, southwestern China. The strain exhibited high pairwise 16 S rRNA gene sequence similarity with Psychromicrobium lacuslunae (97.3%) and Psychromicrobium silvestre (96.3%). Strain YIM S02556T exhibited an average nucleotide identity (ANI) of 72.5% with P. lacuslunae IHBB 11,108T and 72.8% ANI with P. silvestre AK 20-18T. The digital DNA-DNA hybridization (dDDH) value between strain YIM S02556T and P. lacuslunae IHBB 11,108T was 20.2%, while with P. silvestre AK 20-18T, the dDDH value was 20.8%. Strain YIM S02556T exhibited optimal growth at 28 °C, pH 7.0, without NaCl. Growth occurred within 10-37 ℃, pH 5.0-8.0, and in the presence of up to 5% w/v NaCl concentration. The genome size was 3.1 Mbp with 64.2% G + C content. The predominant menaquinone was MK-8(H4). The major cellular fatty acid was anteiso-C15:0. Based on the polyphasic analysis, strain YIM S02556T (= KCTC 49,805T = CCTCC AB2020166T) represents a novel Psychromicrobium species in which the name Psychromicrobium xiongbiense sp.nov. was proposed.

Modulating the Microenvironments of Robust Metal Hydrogen-Bonded Organic Frameworks for Boosting Photocatalytic Hydrogen Evolution.

Hydrogen-bonded organic frameworks (HOFs) are outstanding candidates for photocatalytic hydrogen evolution. However, most of reported HOFs suffer from poor stability and photocatalytic activity in the absence of Pt cocatalyst. Herein, a series of metal HOFs (Co2-HOF-X, X=COOMe, Br, tBu and OMe) have been rationally constructed based on dinuclear cobalt complexes, which exhibit exceptional stability in the presence of strong acid (12 M HCl) and strong base (5 M NaOH) for at least 10 days. More impressively, by varying the -X groups of the dinuclear cobalt complexes, the microenvironment of Co2-HOF-X can be modulated, giving rise to obviously different photocatalytic H2 production rates, following the -X group sequence of -COOMe>-Br>-tBu>-OMe. The optimized Co2-HOF-COOMe shows H2 generation rate up to 12.8 mmol g-1 h-1 in the absence of any additional noble-metal photosensitizers and cocatalysts, which is superior to most reported Pt-assisted photocatalytic systems. Experiments and theoretical calculations reveal that the -X groups grafted on Co2-HOF-X possess different electron-withdrawing ability, thus regulating the electronic structures of Co catalytic centres and proton activation barrier for H2 production, and leading to the distinctly different photocatalytic activity.

Plant-soil hydraulic interaction and rhizosphere bacterial community under biochar and CO2 enrichment.

The increasing atmospheric CO2 concentration is a global concern that affects the plant-bacteria-soil system. Previous studies have investigated plant growth and bacteria activity under CO2 enrichment. However, the effects of coupled elevated CO2 and biochar amendment on the interactions of soil and medicinal plants are not well understood. This study aims to investigate the medicinal plant-soil hydraulic interactions and rhizosphere bacteria communities under coupled CO2 enrichment and biochar conditions. Two levels of CO2 concentration (400, 1000 ppm) and two biochar dosages (3%, 5% by mass) were considered. Pseudostellaria heterophylla was used as the tested medicinal plant. During plant growth, coupled CO2 enrichment and biochar at 3% and 5% dosage increased the volumetric water content at a matric suction of 33 kPa by 97% and 82% respectively, which indicates enhanced water retention. The transpiration rate of P. heterophylla was slightly reduced by 11-30% with an increase in biochar dosage due to higher total suction, while it was significantly reduced by up to 57% due to CO2 enrichment. In the rhizosphere of P. heterophylla, elevated CO2 (1000 ppm) coupled with 3% biochar dramatically increase the relative abundance of Thaumarchaeota, which played an important role in C and N cycles. Moreover, coupled CO2 enrichment and biochar addition resulted in the highest bacterial richness, while 3% biochar at ambient CO2 induced the highest bacterial diversity. This study provides a basis for understanding the medicinal plant-bacteria-soil system under CO2 enrichment and biochar conditions.

Influences of phosphorus-modified biochar on bacterial community and diversity in rhizosphere soil.

Root-associated bacteria play a vital role in the soil ecosystem and plant productivity. Previous studies have reported the decline of bacterial community and rhizosphere soil quality in the cultivation of some medicinal plants (i.e., Pseudostellaria heterophylla). Phosphorus (P)-modified biochar has the potential to improve soil health and quality. However, its influence on the bacterial community and diversity in the rhizosphere of medicinal plants is not well understood. Therefore, this study aims to investigate the effects of P-modified biochar on the bacterial community and diversity in the rhizosphere of P. heterophylla. Soil samples were collected from the rhizosphere of 4-month P. heterophylla under control (no biochar), 3% unmodified and 3% P-modified biochar treatments, respectively. Compared with control and unmodified biochar treatment, P-modified biochar significantly increased the relative abundance of plant-beneficial bacteria (P < 0.05), particularly Firmicutes, Nitrospirae and Acidobacteria. The relative abundance of Bacillus, belonging to Firmicutes, was dramatically raised from 0.032% in control group to 1.723% in P-modified biochar-treated group (P < 0.05). These results indicate the potential enhancement of soil quality for the growth of medicinal plants. The application of biochar significantly increased bacterial richness and bacterial diversity (P < 0.05). P modification of biochar did not have significant effects on soil bacterial richness (P > 0.05), while it reduced Shannon and increased Simpson diversity index of soil bacterial communities significantly (P < 0.05). It indicates a decrease in bacterial diversity. This research provides a new perspective for understanding the role of P-modified biochar in the rhizosphere ecosystem.

Evaluation of body composition and bone mineral density in patients with and without idiopathic condylar resorption of temporomandibular disorders by dual energy X-ray absorptiometry.

Background/purpose: The impact of temporomandibular joint (TMJ) osseous destruction on bone mineral density (BMD) remains unclear due to controversial findings. Besides, no previous study has explored the relationship between idiopathic condylar resorption (ICR) and body composition. This study aimed to investigate the relationship between ICR and BMD or body composition. Materials and methods: Between July 2018 and August 2022, patients evaluated by an experienced dentist and diagnosed with temporomandibular disorders (TMDs) were referred to our center. They were recruited while they received the magnetic resonance image (MRI) examination, BMD and body composition completely. Patients were further categorized into TMDs with or without ICR groups according to MRI findings. One-way analysis of variance was used to compare the variables of BMD and body composition in the two groups. Results: In total, 67 patients were included in the analysis, with 42 categorized as TMDs with ICR and 25 as TMDs without ICR. Patients with ICR had a significantly higher lean mass percentage and lower fat mass percentage; lower android/gynoid fat ratio, and visceral adipose tissue area than those without ICR (P < 0.05). Besides, patients above age 30 with ICR had lower Z scores (P = 0.017) compared with subjects without ICR. Conclusion: TMDs patients with ICR show a relationship with body composition and affect the lean and fat mass distribution, especially android/gynoid fat ratio. The pathophysiological mechanism remains unclear. Further researches to investigate teeth binding, malocclusion and dietary habits are important to understand the association of ICR, BMD and body composition.

[Single mini-incision combined with honeycomb titanium plate in treatment of acute acromioclavicular joint dislocation].

OBJECTIVE: To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation. METHODS: The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods. Among them, 20 patients were fixed with single small incision with honeycomb titanium plate (titanium plate group), including 11 males and 9 females, aged from 23 to 65 years old with an average of (47.40±12.58) years old;12 patients on the left side, 8 patients on the right side;11 patients with type Ⅲ, 3 patients with type Ⅳ, and 6 patients with type Ⅴ according to Rockwood classification. Twenty patients were fixed with clavicular hook plate (clavicular hook group), including 8 males and 12 females, aged from 24 to 65 years old with an average of (48.40±12.08) years old;12 patients on the left side, 8 patients on the right side;10 patients with type Ⅲ, 2 patients with type Ⅳ, and 8 patients with type Ⅴ according to Rockwood classification. Operative time, incision length, intraoperative blood loss, hospital stay, visual analogue scale (VAS) and Constant-Murley score of shoulder joint function were compared between two groups. Anteroposterior radiographs of the affected shoulder joint were recorded before, immediately and 6 months after surgery, and the coracoclavicular distance was measured and compared. RESULTS: Both groups of patients were successfully completed operation without serious complications. All patients were followed up for 6 to 15 months with an average of (11.9±4.8) months. There were no incisional infection, internal plant fracture or failure, bone tunnel fracture and other complications occurred. The incision length of titanium plate group (35.90±3.14) mm was significantly shorter than that of clavicular hook group (49.30±3.79) mm (P<0.05). There were no significant difference in operative time, intraoperative blood loss and hospital stay between two groups (P>0.05). At 1 and 3 months after operation, VAS of titanium plate group was lower than that of clavicular hook group (P<0.05). Connstant-Murley scores in titanium plate group at 1, 3 and 6 months after operation were (86.80±1.36), (91.60±2.32) and (94.90±2.22), respectively;and in clavicular hook group were (78.45±5.47), (85.55±2.01) and (90.25±1.92), which were higher than that of clavicular hook group (P<0.05). There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after operation(P>0.05). CONCLUSION: For the treatment of acute acromioclavicular joint dislocation, single small incision combined with honeycomb titanium plate have advantages of shorter incision, fast recovery of shoulder joint function without the second operation, and has good satisfaction of patient.

Engineered hsa-miR-455-3p-Abundant Extracellular Vesicles Derived from 3D-Cultured Adipose Mesenchymal Stem Cells for Tissue-Engineering Hyaline Cartilage Regeneration.

Efforts are made to enhance the inherent potential of extracellular vesicles (EVs) by utilizing 3D culture platforms and engineered strategies for functional cargo-loading. Three distinct types of adipose mesenchymal stem cells-derived EVs (ADSCs-EVs) are successfully isolated utilizing 3D culture platforms consisting of porous gelatin methacryloyl (PG), PG combined with sericin methacryloyl (PG/SerMA), or PG combined with chondroitin sulfate methacryloyl (PG/ChSMA). These correspond to PG-EVs, PG/SerMA-EVs, and PG/ChSMA-EVs, respectively. Unique microRNA (miRNA) profiles are observed in each type of ADSCs-EVs. Notably, PG-EVs encapsulate higher levels of hsa-miR-455-3p and deliver more hsa-miR-455-3p to chondrocytes, which results in the activation of the hsa-miR-455-3p/PAK2/Smad2/3 axis and the subsequent hyaline cartilage regeneration. Furthermore, the functionality of PG-EVs is optimized through engineered strategies, including agomir/lentivirus transfection, electroporation, and Exo-Fect transfection. These strategies, referred to as Agomir-EVs, Lentivirus-EVs, Electroporation-EVs, and Exo-Fect-EVs, respectively, are ranked based on their efficacy in encapsulating hsa-miR-455-3p, delivering hsa-miR-455-3p to chondrocytes, and promoting cartilage formation via the hsa-miR-455-3p/PAK2/Smad2/3 axis. Notably, Exo-Fect-EVs exhibit the highest efficiency. Collectively, the 3D culture conditions and engineered strategies have an impact on the miRNA profiles and cartilage regeneration capabilities of ADSCs-EVs. The findings provide valuable insights into the mechanisms underlying the promotion of cartilage regeneration by ADSCs-EVs.

Reliability and Validity of the Star Excursion Balance Test for Evaluating Dynamic Balance of Upper Extremities.

BACKGROUND: Upper extremity (UE) dynamic balance is a significant physical fitness ability, which includes high-level neuromuscular proprioception, joint mobility, force, and coordination. The evaluation methods of UE dynamic balance are insufficient and lack experimental support. The Star Excursion Balance Test (SEBT) is a reliable assessment of dynamic balance and injury risk of the lower extremity. HYPOTHESIS: The UE-SEBT is a reliable and reproducible approach for evaluating dynamic balance of UEs. STUDY DESIGN: Observational study. LEVEL OF EVIDENCE: Level 4. METHODS: This cross-sectional study recruited 65 healthy adults. All participants were required to complete UE-SEBT, UE Y-balance test (UE-YBT), maximal voluntary isometric contraction (MVIC) of UE, closed kinetic chain UE stability test (CKCUEST), trunk flexor endurance test (TFET), trunk extensor endurance test (TEET), and lateral trunk endurance test (LTET). Intra- and inter-rater reliability and the correlation of UE-SEBT with other outcomes were measured. RESULTS: Among the participants, the intra- and interoperator reliability of UE-SEBT in all directions and composite score achieved a moderate-to-excellent (intraclass correlation coefficients [ICC], 0.729-0.946) reliability. For validity, the UE-SEBT had a moderate to very strong correlation with UE-YBT (r = 0.315-0.755, P < 0.01) and a strong correlation with CKCUEST (r = 0.4-0.67, P < 0.01). Furthermore, the UE-SEBT performance showed weak-to-strong correlations with MVIC (r = 0.26-0.43, P < 0.05). UE-SEBT was also correlated with LTET, TEET, and TFET to varying degrees. CONCLUSION: UE-SEBT has good reliability and validity to assess UE dynamic balance compared with other tests. CLINICAL RELEVANCE: UE-SEBT can be used as a clinical assessment method to evaluate UE dynamic balance and injury prevention.

Associations between Physical Activity and the Incidence of Cerebrovascular Disease or All-Cause Mortality among 146,742 Older Adults: A 13-Year Prospective Cohort Study.

OBJECTIVES: Although studies have indicated that physical activity (PA) is related to cardiovascular disease, the specific association between PA and incident cerebrovascular disease (CBVD) remains uncertain. The current study aimed to investigate the associations between PA levels and the CBVD incidence or all-cause mortality. DESIGN: Prospective cohort study. SETTINGS AND PARTICIPANTS: Older participants (aged >60 years) from the UK Biobank. METHODS: The baseline PA was classified as total, light, moderate, and vigorous PA based on the metabolic equivalent-minutes per week (MET-min/wk) and considered as exposures, whereas CBVD incidence and all-cause mortality were considered as the outcomes. Cox proportional hazards were used to calculate the hazard ratios (HRs) and 95% CIs for the influence of the association between PA and CBVD incidence and all-cause mortality. RESULTS: A total of 146,742 participants aged 60 years and older were included. During a median follow-up period of 13.5 years (interquartile range of 12.8-14.2), 9338 older individuals developed CBVD and 3033 death were recorded (including 767 CBVD-related deaths). High volumes of PA were consistently associated with lower risks of CBVD and all-cause mortality. The lowest risk of CBVD incidence was observed at 2001-2500 MET-min/wk of total PA (HR 0.61, 95% CI 0.53-0.70), and the lowest risk of all-cause mortality was observed at 2501-5000 MET-min/wk (HR 0.52, 95% CI 0.43-0.63) in older adults. Total PA at 2001-2500 MET-min/wk significantly reduced the CBVD incidence in older women (HR 0.57, 95% CI 0.46-0.71), which was more pronounced than that in older men (HR for 2001-2500 MET-min/wk: 0.64, 95% CI 0.50-0.77). CONCLUSIONS AND IMPLICATIONS: Total PA at 2001-2500 MET-min/wk significantly reduced the risk of incident CBVD and all-cause mortality in adults aged >60 years, although the extents of risk reduction vary in men and women.

Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.