Losses of low-germinating, slow-growing species prevent grassland composition recovery from nutrient amendment.

Nutrient enrichment often alters the biomass and species composition of plant communities, but the extent to which these changes are reversible after the cessation of nutrient addition is not well-understood. Our 22-year experiment (15 years for nutrient addition and 7 years for recovery), conducted in an alpine meadow, showed that soil nitrogen concentration and pH recovered rapidly after cessation of nutrient addition. However, this was not accompanied by a full recovery of plant community composition. An incomplete recovery in plant diversity and a directional shift in species composition from grass dominance to forb dominance were observed 7 years after the nutrient addition ended. Strikingy, the historically dominant sedges with low germination rate and slow growth rate and nitrogen-fixing legumes with low germination rate were unable to re-establish after nutrient addition ceased. By contrast, rapid recovery of aboveground biomass was observed after nutrient cessation as the increase in forb biomass only partially compensated for the decline in grass biomass. These results indicate that anthropogenic nutrient input can have long-lasting effects on the structure, but not the soil chemistry and plant biomass, of grassland communities, and that the recovery of soil chemical properties and plant biomass does not necessarily guarantee the restoration of plant community structure. These findings have important implications for the management and recovery of grassland communities, many of which are experiencing alterations in resource input.

Revolutionizing CO2 Electrolysis: Fluent Gas Transportation within Hydrophobic Porous Cu2O.

The success of electrochemical CO2 reduction at high current densities hinges on precise interfacial transportation and the local concentration of gaseous CO2. However, the creation of efficient CO2 transportation channels remains an unexplored frontier. In this study, we design and synthesize hydrophobic porous Cu2O spheres with varying pore sizes to unveil the nanoporous channel's impact on gas transfer and triple-phase interfaces. The hydrophobic channels not only facilitate rapid CO2 transportation but also trap compressed CO2 bubbles to form abundant and stable triple-phase interfaces, which are crucial for high-current-density electrocatalysis. In CO2 electrolysis, in situ spectroscopy and density functional theory results reveal that atomic edges of concave surfaces promote C-C coupling via an energetically favorable OC-COH pathway, leading to overwhelming CO2-to-C2+ conversion. Leveraging optimal gas transportation and active site exposure, the hydrophobic porous Cu2O with a 240 nm pore size (P-Cu2O-240) stands out among all the samples and exhibits the best CO2-to-C2+ productivity with remarkable Faradaic efficiency and formation rate up to 75.3 ± 3.1% and 2518.2 ± 8.1 µmol h-1 cm-2, respectively. This study introduces a novel paradigm for efficient electrocatalysts that concurrently addresses active site design and gas-transfer challenges.

Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid.

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug-drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these patients. By using a computational and structure-guided approach, we were able to optimize a 100 to 250 µM screening hit to a potent nanomolar inhibitor and lead compound, Mpro61. In this study, we further evaluate Mpro61 as a lead compound, starting with examination of its mode of binding to SARS-CoV-2 Mpro. In vitro pharmacological profiling established a lack of off-target effects, particularly CYP450 3A4 inhibition, as well as potential for synergy with the currently approved alternate antiviral, molnupiravir. Development and subsequent testing of a capsule formulation for oral dosing of Mpro61 in B6-K18-hACE2 mice demonstrated favorable pharmacological properties, efficacy, and synergy with molnupiravir, and complete recovery from subsequent challenge by SARS-CoV-2, establishing Mpro61 as a promising potential preclinical candidate.

Effect of mitochondrial calcium homeostasis-mediated endogenous enzyme activation on tenderness of beef muscle based on MCU modulators.

The mitochondrial calcium uniporter (MCU) occupies a noteworthy position in the regulation of mitochondrial calcium uptake. This study investigated the effects of MCU modulator-mediated mitochondrial calcium on mitochondrial dysfunction, oxidative stress, endogenous enzyme activities, and tenderness during postmortem aging. Spermine, as an activator of MCU, resulted in an increase in mitochondrial calcium levels, not only disrupting mitochondrial morphology but also triggering mitochondrial oxidative stress and downregulation of antioxidant factors. Additionally, the spermine group underwent later activation of calpain and earlier activation of caspases, as well as the myofibril fragmentation index was initially lower and then higher compared with control group, indicating that endogenous enzymes played an indispensable role in different aging periods. Interestingly, the results of the Ru360 (an inhibitor of MCU) group were opposite to those aforementioned findings. Our data provide a novel perspective on the regulatory mechanism of mitochondrial calcium homeostasis mediated by MCU on tenderness.

Mechanism underlying the tenderness evolution of stir-fried pork slices with heating rate revealed by infrared thermal imaging assistance.

This study aimed to explore the mechanism of cooking intensity on the tenderness of stir-fried pork slices from the perspective of the changes in temperature distribution. Infrared thermal imaging was used to monitor the distribution of temperature. Results showed that the high-level heat (HH) treatment could improve tenderness. When the center temperature increased to 100 °C, the shear force of samples from the low-level heat (LH) group increased by around 3-fold, and HH reduced this upward trend. This result was mainly attributed to the shorter heating time undergone by the HH-treated samples compared to the LH treatment, which resulted in less structural shrinkage and faster passing through the protein denaturation interval of the samples. These changes alleviated temperature fluctuations caused by water loss. This explanation could be confirmed by the results of T2 relaxation time and Fourier transform-infrared spectroscopy (FT-IR). However, the LH treatment caused a slower rise in oil temperature due to more moisture migration, which required the samples to undergo longer thermal denaturation, leading to a deterioration in tenderness. Moreover, histological analysis revealed that the greater integrity of endomysium in the HH group inhibited water loss and oil absorption, which contributed to obtain low-fat meat products with higher tenderness. This study provides support for the industrialization of traditional pork cuisines using oil as the heating medium.

The Effect of Enzymatic Hydrolysis and Maillard Reaction on the Flavor of Chicken Osteopontin.

To reveal the changes in the flavor quality of chicken osteopontin (CO) before and after enzymatic hydrolysis and a thermal reaction, the present study was carried out to evaluate the volatile compounds and non-volatile compounds in CO. The results show that the chicken boneset enzymatic solution (CBES) presented a notably richer aroma after the enzymatic hydrolysis treatment. At the same time, the concentrations of the total free amino acids (FAAs) and 5'-nucleotides in the CBES increased dramatically. The ERP (enzymatic reaction paste) scores and the ORC (osteopontin reactive cream) scores were exceptionally high in terms of the umami and salty flavor profiles. As precursors, FAAs and 5'-nucleotides also boosted the Maillard reaction, leading to the generation of wide volatile compounds. Compared to CO, CBES, and ORC, the sensory evaluation showed that ERP scored the highest. In summary, the enzymatic hydrolysis treatment coupled with the Maillard reaction significantly enhanced the flavor profile of CO. These findings offer valuable insights into the high-value utilization of bone by-products, making a significant advancement in the field.

Multi-targeting oligopyridiniums: Rational design for biofilm dispersion and bacterial persister eradication.

The development of effective antibacterial drugs to combat bacterial infections, particularly the biofilm-related infections, remains a challenge. There are two important features of bacterial biofilms, which are well-known critical factors causing biofilms hard-to-treat in clinical, including the dense and impermeable extracellular polymeric substances (EPS) and the metabolically repressed dormant and persistent bacterial population embedded. These characteristics largely increase the difficulty for regular antibiotic treatment due to insufficient penetration into EPS. In addition, the dormant bacteria are insensitive to the growth-inhibiting mechanism of traditional antibiotics. Herein, we explore the potential of a series of new oligopyridinium-based oligomers bearing a multi-biomacromolecule targeting function as the potent bacterial biofilm eradication agent. These oligomers were rationally designed to be "charge-on-backbone" that can offer a special alternating amphiphilicity. This novel and unique feature endows high affinity to bacterial membrane lipids, DNAs as well as proteins. Such a broad multi-targeting nature of molecules not only enables its penetration into EPS, but also plays vital roles in the bactericidal mechanism of action that is highly effective against dormant and persistent bacteria. Our in vitro, ex vivo, and in vivo studies demonstrated that OPc3, one of the most effective derivatives, was able to offer excellent antibacterial potency against a variety of bacteria and effectively eliminate biofilms in zebrafish models and mouse wound biofilm infection models.

Stabilization and strengthening effects of filamentous nanocellulose in the foam forming of quartz paper.

Compared with traditional papermaking, foam forming is a new papermaking technology that uses foam instead of water to disperse fibres, which can effectively solve the problem of poor evenness of ceramic paper, but the instability of foam itself affects the application of foam forming technology. Herein, a highly stable foaming agent for foam forming technology was prepared via physical reaction of lauryl dimethyl amine oxide (OB-2) with filamentous nanocellulose (cellulose nanofiber (CNF-C) and bacterial cellulose (BC)). Then, the quartz paper was prepared by foam forming technology. Firstly, hydrogen bond interactions between hydroxyl groups of the filamentous nanocellulose and hydrophilic moieties on OB-2 enabled the formation of a 3D nanonetwork layer on the surface of the bubble, which extended the half-life of the bubble and effectively prevented the bubble from bursting or coalescing. Then, the foam was extruded and cracked, and the filamentous nanocellulose was retained on the quartz fibres to prepare filamentous nanocellulose/quartz fibre paper by foam forming technology. The quartz paper exhibited excellent evenness and mechanical properties. In conclusion, the research of foam forming technology is of great significance to the application and development of special paper.

Mediation role of perceived social support between recurrence risk perception and health behaviour among patients with stroke in China: a cross-sectional study.

OBJECTIVES: To examine whether patients who had a stroke with high recurrence risk perception would have healthier behaviour and to explore whether perceived social support would function as a mediator. DESIGN: A cross-sectional study. SETTING: The study was conducted in a public tertiary hospital in China. PARTICIPANTS: A total of 254 patients with stroke were invited to participate, and 250 patients with stroke completed questionnaires validly. PRIMARY AND SECONDARY OUTCOME MEASURES: Questionnaires were administered offline to collect data, consisting of four parts: general demographics and scales related to recurrence risk perception, perceived social support, and health behaviour. A path analysis and correlation analysis were used to analyse the data. RESULTS: Out of 250 patients with stroke, 78.4% had moderately low health behaviour. The majority (70.8%) of these patients were elderly. High recurrence risk perception and high perceived social support were significantly associated with better health behaviour (all p<0.001). Perceived social support mediated the relationship between recurrence risk perception and health behaviour after controlling for age, gender, education and monthly income in the regression model (95% CI 0.263 to 0.460) and the effect value was 0.360. It was also confirmed that perceived social support had the highest mediation effect with a proportion of mediation up to 59.31%. CONCLUSIONS: Recurrence risk perception and perceived social support were influential factors in promoting health behaviour. Moreover, the impact of recurrence risk perception on health behaviour was partially mediated by perceived social support. Therefore, to enhance the sustainability of health behaviour, it is crucial to inform patients with stroke about the risk of recurrence. Patients with more perception of recurrence risk can improve their recovery confidence and thus perceive more social support.

Prediction of Non-Transplantable Recurrence After Liver Resection for Solitary Hepatocellular Carcinoma.

Purpose: Using a combination model of preoperative imaging and clinical factors to predict non-transplantable recurrence (NTR) after liver resection and assist solitary hepatocellular carcinoma (HCC) patients in the selection of early treatment options. Patients and Methods: A retrospective analysis was conducted on 253 solitary HCC patients who underwent radical resection and had preoperative MRI. NTR patients were defined as those exceeding the University of California, San Francisco (UCSF) criteria at the time of recurrence. Cox regression analysis was employed to identify preoperative factors associated with NTR based on clinical and tumor imaging characteristics. A risk scoring model (NTRScore) was developed and validated. Results: Among the 253 patients, 86 (33.9%) experienced recurrence, and among those with recurrence, 34 patients (39.5%) developed NTR. In multivariate analysis, factors associated with NTR included alpha-fetoprotein (AFP) [>10 ng/mL] [HR: 3.42, 95% confidence interval (CI): 1.54-7.63, P: 0.003], arterial phase hyperenhancement (APHE) [HR: 2.23, 95% CI: 1.03-4.81, P: 0.041], washout[HR: 0.35, 95% CI: 0.15-0.84, P: 0.019], and capsule [HR: 0.44, 95% CI: 0.22-0.88, P: 0.021]. The ß-coefficients of these variables were utilized to develop the weighted NTRScore(c-index 0.72, 95% CI: 0.65-0.79). The NTR occurrence increased across the three categories (low: 5.6%, medium: 13.6%, high: 35.1%, p < 0.001), and the Kaplan-Meier curves of recurrence-free survival(RFS) and overall survival(OS) show significant differences (p = 0.004 and p<0.001). Furthermore, the higher NTR categories may be associated with an increased risk of extrahepatic recurrence. Conclusion: The NTRScore demonstrated strong discriminatory ability and may serve as a clinically useful tool to assist in risk stratification and potential to guide treatment and optimal surveillance for patients of solitary hepatocellular carcinoma within UCSF criteria.

Superaerophilic/Superaerophobic NiFe-LDHs Electrode for Enhancing Overall Water Splitting in Alkaline Media.

Overall water splitting, as a critical approach to producing green hydrogen, is greatly impeded by the mass transfer of gaseous bubbles and dissolved gas molecules. Herein, a bifunctional superaerophilic/superaerophobic (SAL/SAB) NiFe layered-double-hydroxides (LDHs) electrode has been developed, which can drive H2 and O2 bubbles out of the reaction system by asymmetric Laplace pressure and accelerate dissolved gases diffusion through reducing their diffusion distance. Consequently, the SAL/SAB NiFe-LDHs electrode exhibits excellent HER activity with an overpotential of -76 mV at -10 mA cm-2 and outstanding oxygen evolution reaction activity with an overpotential of 253 mV at 100 mA cm-2. The bifunctional SAL/SAB NiFe-LDHs electrode is further utilized in overall water splitting, which can achieve 10 mA cm-2 with a cell voltage of 1.54 V. This work provides an efficient strategy to improve the efficiency of overall water splitting and can stimulate new electrode design in various gas-involved processes.

A potential mechanism clue to the periodic storm from microglia activation and progressive neuron damage induced by paraquat exposure.

Paraquat (PQ), is characterized by neurotoxicity, which increases the potential risk of Parkinson's disease (PD) exposure in the long-term and low doses. Triggering microglia activation and neuroinflammation is deemed an early event resulting in PD. However, the underlying pathogenesis of PD by PQ is not clear yet. In this article, C57BL/6J mice treated with PQ could successfully act out Parkinson-like. In addition, we observed the fluorescence intensity enhancement of Iba-1 activated microglia with released pro-inflammatory, all ahead of both the damage of dopaminergic neurons in the substantia nigra and corpus striatum of the brain. Surprisingly, the injection of minocycline before PQ for many hours not only can effectively improve the neurobehavioral symptoms of mice but inhibit the activation of microglia and the release of pro-inflammatory substances, even controlling the gradual damage and loss of neurons. A further mechanism of minocycline hampered the expression levels of key signaling proteins PI3K, PDK1, p-AKT, and CD11b (the receptor of microglia membrane recognition), while a large number of inflammatory factors. Our results suggested that the CD11b/PI3K/NOX2 pathway may be a clue that microglia-mediated inflammatory responses and neuronal damage in a PQ-induced abnormal behavior Parkinson-like mouse.

To What Extent Do Low-Voltage Electrostatic Fields Play a Role in the Physicochemical Properties of Pork during Freezing and Storage?

Low-voltage electrostatic fields (LVEF) are recognized as a new technology that can improve the quality of frozen meat. To determine the extent to which LVEF assistance affects the quality of frozen pork for long-term storage, pork was frozen and stored at -18 and -38 °C for up to 5 months. Water-holding capacity, muscle microstructure, and protein properties were investigated after up to 5 months of frozen storage with and without LVEF assistance. In comparison to traditional -18 and -38 °C frozen storage, LVEF treatment inhibited water migration during frozen storage and thawing. As a result, thawing losses were reduced by 15.97% (-18 °C) and 3.38% (-38 °C) in LVEF-assisted compared to conventional freezing methods. LVEF helped to maintain the muscle fiber microstructure and reduce muscle protein denaturation by miniaturizing ice crystal formation by freezing. As a result of this study, LVEF is more suitable for freezing or short-term frozen storage, while a lower temperature plays a more significant role in long-term frozen storage.

Size characterization of x-ray tube source with sphere encoded imaging method.

In x-ray imaging, the size of the x-ray tube light source significantly impacts image quality. However, existing methods for characterizing the size of the x-ray tube light source do not meet measurement requirements due to limitations in processing accuracy and mechanical precision. In this study, we introduce a novel method for accurately characterizing the size of the x-ray tube light source using spherical encoded imaging technology. This method effectively mitigates blurring caused by system tilting, making system alignment and assembly more manageable. We employ the Richardson-Lucy algorithm to iteratively deconvolve the image and recover spatial information about the x-ray tube source. Unlike traditional coded imaging methods, spherical coded imaging employs high-Z material spheres as coding elements, replacing the coded holes used in traditional approaches. This innovation effectively mitigates blurring caused by system tilting, making system alignment and assembly more manageable. In addition, the mean square error is reduced to 0.008. Our results demonstrate that spherical encoded imaging technology accurately characterizes the size of the x-ray tube light source. This method holds significant promise for enhancing image quality in x-ray imaging.

Screening and Stability Evaluation of Freeze-Dried Protective Agents for a Live Recombinant Pseudorabies Virus Vaccine.

Infection of pigs with the pseudorabies virus (PRV) causes significant economic losses in the pig industry. Immunization with live vaccines is a crucial aspect in the prevention of pseudorabies in swine. The TK/gE/gI/11k/28k deleted pseudorabies vaccine is a promising alternative for the eradication of epidemic pseudorabies mutant strains. This study optimized the lyophilization of a heat-resistant PRV vaccine to enhance the quality of a live vaccine against the recombinant PRV rHN1201TK-/gE-/gI-/11k-/28k-. The A4 freeze-dried protective formulation against PRV was developed by comparing the reduction in virus titer after lyophilization and after seven days of storage at 37 °C. The formulation contains 1% gelatin, 5% trehalose, 0.5% poly-vinylpyrimidine (PVP), 0.5% thiourea, and 1% sorbitol. The A4 freeze-dried vaccine demonstrated superior protection and thermal stability. It experienced a freeze-dried loss of 0.31 Lg post-freeze-drying and a heat loss of 0.42 Lg after being stored at a temperature of 37 °C for 7 consecutive days. The A4 freeze-dried vaccine was characterized through XRD, FTIR, and SEM analyses, which showed that it possessed an amorphous structure with a consistent porous interior. The trehalose component of the vaccine formed stable hydrogen bonds with the virus. Long-term and accelerated stability studies were also conducted. The A4 vaccine maintained viral titer losses of less than 1.0 Lg when exposed to 25 °C for 90 days, 37 °C for 28 days, and 45 °C for 7 days. The A4 vaccine had a titer loss of 0.3 Lg after storage at 2-8 °C for 24 months, and a predicted shelf life of 6.61 years at 2-8 °C using the Arrhenius equation. The A4 freeze-dried vaccine elicited no side effects when used to immunize piglets and produced specific antibodies. This study provides theoretical references and technical support to improve the thermal stability of recombinant PRV rHN1201TK-/gE-/gI-/11k-/28k- vaccines.

Low-voltage electrostatic field enhances the frozen force of -12 ℃ to suppress oxidative denaturation of the lamb protein during the subsequent frozen storage process after finishing initial freezing.

The effect of low-voltage electrostatic field (LVEF) assisted -9 °C (LVEF-9) and -12 °C (LVEF-12) frozen, non-LVEF-assisted -9 °C (NLVEF-9) and -12 °C (NLVEF-12) frozen, and conventional frozen (CF-18, -18 °C) storage on the muscle microstructure and the oxidative denaturation of the lamb protein during the subsequent frozen storage process after finishing initial freezing was investigated. Compared with NLVEF-9, LVEF-9, and NLVEF-12, LVEF-12 maintained the better integrity of muscle microstructure, demonstrated by smaller holes, more complete Z-line and M-line, and no significant difference with CF-18 (P > 0.05). Furthermore, LVEF-12 effectively inhibited protein oxidative denaturation as shown by the lower carbonyl content, surface hydrophobicity, and higher total/active sulfhydryl groups and Ca2+-ATPase activity. Moreover, LVEF-12 effectively maintained the integrity of the secondary and tertiary structure of proteins, reduced cross-linking aggregation of proteins, and sustained better functional properties, as shown by higher α-helix content, fluorescence intensity, protein solubility, and lower R-value, disulfide bonds.

Novel Calcium-Binding Peptide from Bovine Bone Collagen Hydrolysates and Its Potential Pro-Osteogenic Activity via Calcium-Sensing Receptor (CaSR).

SCOPE: This paper aims to explore the osteogenic activity and potential mechanism of the peptide-calcium chelate, and provides a theoretical basis for peptide-calcium chelates as functional foods to prevent or improve osteoporosis. METHODS AND RESULTS: In this research, a novel peptide (Phe-Gly-Leu, FGL) with a high calcium-binding capacity is screened from bovine bone collagen hydrolysates (CPs), calcium binding sites of which mainly included carbonyl, amino and carboxyl groups. The FGL-Ca significantly enhances the osteogenic activity of MC3T3-E1 cells (survival rate, differentiation, and mineralization). The results of calcium fluorescence labeling and molecular docking show that FGL-Ca may activate calcium-sensing receptor (CaSR), leading to an increase in intracellular calcium concentration, then enhancing osteogenic activity of MC3T3-E1 cells. Further research found that FGL-Ca significantly promotes the mRNA and protein expression levels of CaSR, transforming growth factor ß (TGF-ß1), TGF-ß-type II receptor (TßRII), Smad2, Smad3, osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegrin (OPG), and collagen type I (COLI). Subsequently, in the signal pathway intervention experiment, the expression levels of genes and proteins related to the TGF-ß1/Smad2/3 signaling pathway that are promoted by FGL-Ca are found to decrease. CONCLUSIONS: These results suggest that FGL-Ca may activate CaSR, increase intracellular calcium concentration, and activate TGF-ß1/Smad2/3 signaling pathway, which may be one of the potential mechanisms for enhancing osteogenic activity.

Phosphorylation modification of bovine bone collagen peptide enhanced its effect on mineralization of MC3T3-E1 cells via improving calcium-binding capacity.

This study aimed to investigate the effect of phosphorylation modification of collagen peptide on its calcium-binding capacity and pro-mineralization activity. In this study, collagen peptide (Leu-Thr-Phe, LTF) and phosphorylated LTF (P-LTF) were synthesized and further chelated with calcium ions. The results showed that phosphorylation of LTF significantly enhanced its calcium-binding capacity. Spectra analysis revealed that the calcium-binding sites of P-LTF were mainly carbonyl, carboxyl, and phosphate groups. Molecular docking further demonstrated that the phosphate group introduced by phosphorylation enhanced the calcium-binding capacity of LTF by ionic bonds and coordination bonds. The stability analysis results suggested that intestinal fluid could repair the peptide-calcium complex destroyed by gastric fluid. The cell experiment displayed that P-LTF-Ca significantly improved the mineralization activity of MC3T3-E1 cells, and the order of effective influence was P-LTF-Ca > LTF-Ca > P-LTF > LTF. This study provided the theoretical basis for the potential application of phosphorylation modification in improving bone health.