Synergistic Effect of P and Co Dual Doping Endows CuNi with High-Performance Hydrogen Evolution Reaction.

The rational design of highly active and durable non-noble electrocatalysts for hydrogen evolution reaction (HER) is significantly important but technically challenging. Herein, a phosphor and cobalt dual doped copper-nickel alloy (P, Co-CuNi) electrocatalyst with high-efficient HER performance is prepared by one-step electrodeposition method and reported for the first time. As a result, P, Co-CuNi only requires an ultralow overpotential of 56 mV to drive the current density of 10 mA cm-2, with remarkable stability for over 360 h, surpassing most previously reported transition metal-based materials. It is discovered that the P doping can simultaneously increase the electrical conductivity and enhance the corrosion resistance, while the introduction of Co can precisely modulate the sub-nanosheets morphology to expose more accessible active sites. Moreover, XPS, UPS, and DFT calculations reveal that the synergistic effect of different dopants can achieve the most optimal electronic structure around Cu and Ni, causing a down-shifted d-band center, which reduces the hydrogen desorption free energy of the rate-determining step (H2O + e- + H* → H2 + OH-) and consequently enhances the intrinsic activity. This work provides a new cognition toward the development of excellent activity and stability HER electrocatalysts and spurs future study for other NiCu-based alloy materials.

Electroacupuncture improves gastrointestinal motility through a central-cholinergic pathway-mediated GDNF releasing from intestinal glial cells to protect intestinal neurons in Parkinson's disease rats.

Constipation symptoms of Parkinson's disease (PD) seriously reduce the quality of life of patients and aggravate the development of the disease, but current treatment options still cannot alleviate the progress of constipation. Electroacupuncture (EA) is a new method for the treatment of constipation, which can effectively treat the symptoms of constipation in PD patients. However, the specific regulatory mechanisms of EA in the treatment of constipation symptoms in PD remain unclear. The aim of this study is to investigate the therapeutic effect of EA on PD constipation rats and its regulatory mechanism. A rotenone (ROT)-induced gastrointestinal motility disorder model was used to simulate the pathological process of constipation in PD. The results showed that EA could effectively promote gastrointestinal peristalsis, reduce α-synuclein accumulation in substantia nigra and colon and colonic injury in rats after ROT administration. Mechanistically, EA activation of the central-cholinergic pathway increases acetylcholine release in the colon. At the same time, EA up-regulated the co-expression of enteric glial cells (EGCs) and α7 nicotinic acetylcholine receptor (α7nAChR). EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats. Further mechanistic studies showed that EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues. The present study confirmed that EA upregulates α7nAChR through a central-cholinergic mechanism to promote GDNF release from EGCs, thereby protecting intestinal neurons and thereby improving gastrointestinal motility.

Photoactivated Formation of an Extravascular Dynamic Hydrogel as an Intelligent Blood Flow Regulator to Reprogram the Immunogenic Landscape.

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

Phenotypic characterization and genomic analysis of Limosilactobacillus fermentum phage.

Limosilactobacillus (L.) fermentum is widely utilized for its beneficial properties, but lysogenic phages can integrate into its genome and can be induced to enter the lysis cycle under certain conditions, thus accomplishing lysis of host cells, resulting in severe economic losses. In this study, a lysogenic phage, LFP03, was induced from L. fermentum IMAU 32510 by UV irradiation for 70 s. The electron microscopy showed that this phage belonged to Caudoviricetes class. Its genome size was 39,556 bp with a GC content of 46.08%, which includes 20 functional proteins. Compared with other L. fermentum phages, the genome of phage LFP03 exhibited deletions, inversions and translocations. Biological analysis showed that its optimal multiplicity of infection was 0.1, with a burst size of 133.5 ± 4.9 PFU/infective cell. Phage LFP03 was sensitive to temperature and pH value, with a survival rate of 48.98% at 50 °C. It could be completely inactivated under pH 2. The adsorption ability of this phage was minimally affected by temperature and pH value, with adsorption rates reaching 80% under all treated conditions. Divalent cations could accelerate phage adsorption, while chloramphenicol expressed little influence. This study might expand the related knowledge of L. fermentum phages, and provide some theoretical basis for improving the stability of related products and establishing phage control measures.

Targeted degradation of oncogenic BCR-ABL by silencing the gene of NEDD8 E3 ligase RAPSYN.

Tyrosine kinase inhibitors have been the standard treatment for patients with Philadelphia chromosome-positive (Ph+) leukemia. However, a series of issues, including drug resistance, relapse and intolerance, are still an unmet medical need. Here, we report the targeted siRNA-based lipid nanoparticles in Ph+ leukemic cell lines for gene therapy of Ph+ leukemia, which specifically targets a recently identified NEDD8 E3 ligase RAPSYN in Ph+ leukemic cells to disrupt the neddylation of oncogenic BCR-ABL. To achieve the specificity for Ph+ leukemia therapy, a single-chain fragment variable region (scFv) of anti-CD79B monoclonal antibody was covalently conjugated on the surface of OA2-siRAPSYN lipid nanoparticles to generate the targeted lipid nanoparticles (scFv-OA2-siRAPSYN). Through effectively silencing RAPSYN gene in leukemic cell lines by the nanoparticles, BCR-ABL was remarkably degraded accompanied by the inhibition of proliferation and the promotion of apoptosis. The specific targeting, therapeutic effects and systemic safety were further evaluated and demonstrated in cell line-derived mouse models. The present study has not only addressed the clinical need of Ph+ leukemia, but also enabled gene therapy against a less druggable target.

First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: In the primary analysis report of the GAIA/CLL13 trial, we found that venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib improved undetectable measurable residual disease (MRD) rates and progression-free survival compared with chemoimmunotherapy in patients with previously untreated chronic lymphocytic leukaemia. However, to our knowledge, no data on direct comparisons of different venetoclax-based combinations are available. METHODS: GAIA/CLL13 is an open-label, randomised, phase 3 study conducted at 159 sites in ten countries in Europe and the Middle East. Eligible patients were aged 18 years or older, with a life expectancy of at least 6 months, an Eastern Cooperative Oncology group performance status of 0-2, a cumulative illness rating scale score of 6 or lower or a single score of 4 or lower, and no TP53 aberrations. Patients were randomly assigned (1:1:1:1), with a computer-generated list stratified by age, Binet stage, and regional study group, to either chemoimmunotherapy, venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. All treatments were administered in 28-day cycles. Patients in the chemoimmunotherapy group received six cycles of treatment, with patients older than 65 years receiving intravenous bendamustine (90 mg/m2, days 1-2), whereas patients aged 65 years or younger received intravenous fludarabine (25 mg/m2, days 1-3) and intravenous cyclophosphamide (250 mg/m2, days 1-3). Intravenous rituximab (375 mg/m2, day 1 of cycle 1; 500 mg/m2, day 1 of cycles 2-6) was added to chemotherapy. In the experimental groups, patients received daily venetoclax (400 mg orally) for ten cycles after a 5-week ramp-up phase starting on day 22 of cycle 1. In the venetoclax-rituximab group, intravenous rituximab (375 mg/m2, day 1 of cycle 1; 500 mg/m2, day 1 of cycles 2-6) was added. In the obinutuzumab-containing groups, obinutuzumab was added (cycle 1: 100 mg on day 1, 900 mg on day 2, and 1000 mg on days 8 and 15; cycles 2-6: 1000 mg on day 1). In the venetoclax-obinutuzumab-ibrutinib group, daily ibrutinib (420 mg orally, from day 1 of cycle 1) was added until undetectable MRD was reached in two consecutive measurements (3 months apart) or until cycle 36. The planned treatment duration was six cycles in the chemoimmunotherapy group, 12 cycles in the venetoclax-rituximab and the venetoclax-obinutuzumab group and between 12 and 36 cycles in the venetoclax-obinutuzumab-ibrutinib group. Coprimary endpoints were the undetectable MRD rate in peripheral blood at month 15 for the comparison of venetoclax-obinutuzumab versus standard chemoimmunotherapy and investigator-assessed progression-free survival for the comparison of venetoclax-obinutuzumab-ibrutinib versus standard chemoimmunotherapy, both analysed in the intention-to-treat population (ie, all patients randomly assigned to treatment) with a split α of 0·025 for each coprimary endpoint. Both coprimary endpoints have been reported elsewhere. Here we report a post-hoc exploratory analysis of updated progression-free survival results after a 4-year follow-up of our study population. Safety analyses included all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT02950051, recruitment is complete, and all patients are off study treatment. FINDINGS: Between Dec 13, 2016, and Oct 13, 2019, 1080 patients were screened and 926 were randomly assigned to treatment (chemoimmunotherapy group n=229; venetoclax-rituximab group n=237; venetoclax-obinutuzumab group n=229; and venetoclax-obinutuzumab-ibrutinib group n=231); mean age 60·8 years (SD 10·2), 259 (28%) of 926 patients were female, and 667 (72%) were male (data on race and ethnicity are not reported). At data cutoff for this exploratory follow-up analysis (Jan 31, 2023; median follow-up 50·7 months [IQR 44·6-57·9]), patients in the venetoclax-obinutuzumab group had significantly longer progression-free survival than those in the chemoimmunotherapy group (hazard ratio [HR] 0·47 [97·5% CI 0·32-0·69], p<0·0001) and the venetoclax-rituximab group (0·57 [0·38-0·84], p=0·0011). The venetoclax-obinutuzumab-ibrutinib group also had a significantly longer progression-free survival than the chemoimmunotherapy group (0·30 [0·19-0·47]; p<0·0001) and the venetoclax-rituximab group (0·38 [0·24-0·59]; p<0·0001). There was no difference in progression-free survival between the venetoclax-obinutuzumab-ibrutinib and venetoclax-obinutuzumab groups (0·63 [0·39-1·02]; p=0·031), and the proportional hazards assumption was not met for the comparison between the venetoclax-rituximab group versus the chemoimmunotherapy group (log-rank p=0·10). The estimated 4-year progression-free survival rate was 85·5% (97·5% CI 79·9-91·1; 37 [16%] events) in the venetoclax-obinutuzumab-ibrutinib group, 81·8% (75·8-87·8; 55 [24%] events) in the venetoclax-obinutuzumab group, 70·1% (63·0-77·3; 84 [35%] events) in the venetoclax-rituximab group, and 62·0% (54·4-69·7; 90 [39%] events) in the chemoimmunotherapy group. The most common grade 3 or worse treatment-related adverse event was neutropenia (114 [53%] of 216 patients in the chemoimmunotherapy group, 109 [46%] of 237 in the venetoclax-rituximab group, 127 [56%] of 228 in the venetoclax-obinutuzumab group, and 112 [48%] of 231 in the venetoclax-obinutuzumab-ibrutinib group). Deaths determined to be associated with study treatment by the investigator occurred in three (1%) patients in the chemoimmunotherapy group (n=1 due to each of sepsis, metastatic squamous cell carcinoma, and Richter's syndrome), none in the venetoclax-rituximab and venetoclax-obinutuzumab groups, and four (2%) in the venetoclax-obinutuzumab-ibrutinib group (n=1 due to each of acute myeloid leukaemia, fungal encephalitis, small-cell lung cancer, and toxic leukoencephalopathy). INTERPRETATION: With more than 4 years of follow-up, venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib significantly extended progression-free survival compared with both chemoimmunotherapy and venetoclax-rituximab in previously untreated, fit patients with chronic lymphocytic leukaemia, thereby supporting their use and further evaluation in this patient group, while still considering the higher toxicities observed with the triple combination. FUNDING: AbbVie, Janssen, and F Hoffmann-La Roche.

Plant growth-promoting rhizobacteria (PGPR) improve the growth and quality of several crops.

Plant growth-promoting rhizobacteria (PGPR) are known to have the effect of promoting plant growth. In this paper, three PGPR strains were selected from the previous work, which had plant growth-promoting activities such as phosphate solubilization, nitrogen fixation, phosphorus mobilization, etc. These strains named FJS-3(Burkholderia pyromania), FJS-7(Pseudomonas rhodesiae), and FJS-16(Pseudomonas baetica), respectively, were prepared into solid biological agents. Three widely planted commercial crops (tea plant, tobacco, and chili pepper) were selected for PGPR growth promotion verification. The results showed that the new shoots of tea seedlings under PGPR treatment were much more than the control. We also used tobacco, another important crop in Guizhou, to test the growth-promoting effect of individual bacteria, and the results showed that each of them could promote the growth of tobacco plants, and FJS-3(Burkholderia pyrrocinia) had the best effect. In addition, we carried out experiments on tobacco and pepper using multi-strain PGPR, the tobacco plants' height, fresh, and root weight increased by 30.15 %, 37.36 %, and 54.5 %, respectively, and the pepper plants' increased by 30.10 %, 56.38 % and 43.18 %, respectively, which both showed significantly better effects than that of a single strain. To further test the field performance, field trials were carried out in a mature Longjing43 tea plantation in Guizhou. There were four treatments: no fertilization (T1), combined application of PGPR biological agent and compound fertilizer (T2), only application of PGPR (T3), and only application of compound fertilizer (T4). In terms of yield, grouped with or without PGPR, there was a 15.38 % (T2:T4) and 92.31 % (T3:T1) increase between them, respectively. The tea's yield and tea flavor substances such as tea polyphenols, caffeine, and theanine were detected, and the T2 showed the most significant positive effect on both sides. Especially, an important indicator of Matcha green tea is the color, chlorophyll content was then tested, and PGPR application increased it and improved the appearance. All these results demonstrated that the PGPR we screened could significantly promote plant growth and quality improvement, and had good application potential in crop planting, which could contribute to environmental protection and economic growth.

Location matters: altered interhemispheric homotopic connectivity in post-stroke dyskinesia.

Background: Motor impairment is the most prevalent consequence following a stroke. Interhemispheric homotopic connectivity, which varies regionally and hierarchically along the axis of the somatomotor-association cortex, plays a critical role in sustaining normal motor functions. However, the impact of strokes occurring in various locations on homotopic connectivity is not fully understood. This study aimed to explore how motor deficits resulting from acute strokes in different locations influence homotopic connectivity. Methods: Eighty-four acute ischemic stroke patients with dyskinesia were recruited and divided into four demographically-matched subgroups based on stroke locations: Group 1 (G1; frontoparietal, n = 15), Group 2 (G2; radiation coronal, n = 16), Group 3 (G3; basal ganglia, n = 30), and Group 4 (G4; brain stem, n = 23). An additional 37 demographically-matched healthy controls were also recruited in the study. Multimodal MRI data, motor function assessments, and cognitive tests were gathered for analysis. Interhemispheric homotopic functional and structural connectivity were measured using resting-state functional MRI and diffusion tensor imaging, respectively. These measurements were then correlated with motor function scores to investigate the relationships. Results: Voxel-mirrored homotopic connectivity (VMHC) analysis showed that strokes in the frontoparietal and basal ganglia regions led to diminished homotopic connectivity in the somatosensory/motor cortex. In contrast, strokes in the radiation coronal and brainstem regions affected subcortical motor circuits. Structural homotopic connectivity analysis using diffusion tensor imaging showed that frontoparietal and basal ganglia strokes predominantly affected association fibers, while radiation coronal and brainstem strokes caused widespread disruption in the integrity of both cortical-cortical and cortical-subcortical white matter fibers. Correlation analyses demonstrated significant associations between the Fugl-Meyer Assessment (FMA), Modified Barthel Index (MBI), and National Institutes of Health Stroke Scale (NIHSS) scores with the VMHC in the inferior temporal gyrus for G1 (G1; r = 0.838, p < 0.001; r = 0.793, p < 0.001; and r = -0.834, p < 0.001, respectively). No statistically significant associations were observed in Groups 2, 3, and 4. Conclusion: Our results suggest that motor deficits following strokes in various regions involve distinct pathways from cortical to subcortical areas. Alterations in lesion topography and regional functional homotopy provide new insights into the understanding of neural underpinnings of post-stroke dyskinesia.

National trends in nine key minerals intake (quantity and source) among U.S. adults, 1999 to march 2020.

BACKGROUND: Changes in economy and dietary guidelines brought a great shock to diet quality and meal behaviors, but if these transformations have extended to minerals intake and their sources was still poorly understood. It is essential to evaluate time trends in minerals intake and their sources to inform policy makers. OBJECTIVE: To investigate trends in minerals intake and their sources among U.S. adults. METHODS: This analysis used dietary data collected by 24-h recalls from U.S. adults (≥ 20 years) in NHANES (1999-March 2020). Minerals intake, age-adjusted percentage of participants meeting recommendations, and minerals sources were calculated among all participants and by population subgroups in each NHANES survey cycle. Weighted linear or logistic regression models were used to examine the statistical significance of time trends. RESULTS: A total of 48223 U.S. adults were included in this analysis. From 1999 to March 2020, intake of calcium (from 0.94 to 1.02 g/day), magnesium (from 308.07 to 321.85 mg/day), phosphorus (from 1.24 to 1.30 g/day), and sodium (from 3.24 to 3.26 mg/day) from food and beverages (FB) and dietary supplements (DSs) significantly increased, and intake of iron (from 19.17 to 16.38 mg/day), zinc (from 16.45 to 14.19 mg/day), copper (from 1.79 to 1.38 mg/day), and potassium (from 2.65 to 2.50 g/day) from FB + DSs decreased (all FDR < 0.05). Additionally, age-adjusted percentage of participants meeting recommendations for calcium, phosphorus, sodium, and selenium significantly increased, that for iron, potassium, zinc, and copper decreased (all FDR < 0.05). Minerals intake and time trends in minerals intake were highly variable depending on age, gender, race/ethnicity, education, and income. For example, white, higher socioeconomic status participants had a higher minerals intake (e.g. iron, zinc, and copper), but had a greater decrease in minerals intake. Furthermore, the percentage of minerals from milks and DSs decreased, and that from beverages increased. CONCLUSION: From 1999 to March 2020, both minerals intake and their sources experienced a significant alteration among U.S. adults. Many differences in minerals intake and their food sources across sociodemographic characteristics appeared to narrow over time. Although some improvements were observed, important challenges, such as overconsumption of sodium and underconsumption of potassium, calcium, and magnesium, still remained among U.S. adults.

Spatiotemporally Controlled T-Cell Combination Therapy for Solid Tumor.

Due to multidimensional complexity of solid tumor, development of rational T-cell combinations and corresponding formulations is still challenging. Herein, a triple combination of T cells are developed with Indoleamine 2,3-dioxygenase inhibitors (IDOi) and Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). To maximize synergism, a spatiotemporally controlled T-cell engineering technology to formulate triple drugs into one cell therapeutic, is established. Specifically, a sequentially responsive core-shell nanoparticle (SRN) encapsulating IDOi and CDK4/6i is anchored onto T cells. The yielded SRN-T cells migrated into solid tumor, and achieved a 1st release of IDOi in acidic tumor microenvironment (TME). Released IDOi restored tryptophan supply in TME, which activated effector T cells and inhibited Tregs. Meanwhile, 1st released core is internalized by tumor cells and degraded by glutathione (GSH), to realize a 2nd release of CDK4/6i, which induced up-regulated expression of C-X-C motif chemokine ligand 10 (CXCL10) and C-C motif chemokine ligand 5 (CCL5), and thus significantly increased tumor infiltration of T cells. Together, with an enhanced recruitment and activation, T cells significantly suppressed tumor growth, and prolonged survival of tumor-bearing mice. This study demonstrated rationality and superiority of a tri-drug combination mediated by spatiotemporally controlled cell-engineering technology, which provides a new treatment regimen for solid tumor.

Characterization of Fusarium species causing soybean root rot in Heilongjiang, China, and mechanism underlying the differences in sensitivity to DMI fungicides.

Soybean root rot is a worldwide soil-borne disease threatening soybean production, causing large losses in soybean yield and quality. Fusarium species are the most detrimental pathogens of soybean root rot worldwide, causing large production losses. Fusarium root rot has been frequently reported in Heilongjiang Province of China, but the predominant Fusarium species and the sensitivity of these pathogens to different fungicides remain unclear. In this study, diseased soybean roots were collected from 14 regions of Heilongjiang province in 2021 and 2022. A total of 144 isolates of Fusarium spp. were isolated and identified as seven distinct species: F. scirpi, F. oxysporum, F. graminearum, F. clavum, F. acuminatum, F. avenaceum, and F. sporotrichioide. F. scirpi and F. oxysporum had high separation frequency and strong pathogenicity. The sensitivity of Fusarium spp. to five different fungicides was determined. Mefentrifluconazole and fludioxonil showed good inhibitory effects, and the sensitivity to pydiflumetofen and phenamacril varied between Fusarium species. In particular, the activity of DMI fungicide prothioconazole was lower than that of mefentrifluconazole. Molecular docking showed that mefentrifluconazole mainly bound to CYP51C, but prothioconazole mainly bound to CYP51B. Furthermore, the sensitivity to prothioconazole only significantly decreased in ΔFgCYP51B mutant, and the sensitivity to mefentrifluconazole changed in ΔFgCYP51C and ΔFgCYP51A mutants. The results demonstrated that the predominant Fusarium species causing soybean root rot in Heilongjiang province were F. scirpi and F. oxysporum and DMI fungicides had differences in binding cavity due to the diversity of CYP51 proteins in Fusarium.

Protocol for identifying stressed granulocytes from septic mice.

Sepsis trains stressed granulocytes to boost nonspecific response and trigger a new wave of inflammation when facing secondary infection. Here, we present a protocol for a murine model of sepsis with secondary infection. We describe steps for cecal ligation and puncture operation and rechallenging with lipopolysaccharide or Pseudomonas aeruginosa during the recovery phase. We also detail steps to characterize the stressed granulocytes by assessing their functional phenotypes and effect on the mortality of rechallenged mice. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

Molecular Imaging of Alzheimer's Disease-Related Sigma-1 Receptor in the Brain via a Novel Ru-Mediated Aromatic 18F-deoxyfluorination Probe.

Sigma-1 receptor (σ1R) is an intracellular protein implicated in a spectrum of neurodegenerative conditions, notably Alzheimer's disease (AD). Positron emission tomography (PET) imaging of brain σ1R could provide a powerful tool for better understanding the underlying pathomechanism of σ1R in AD. In this study, we successfully developed a 18F-labeled σ1R radiotracer [18F]CNY-05 via an innovative ruthenium (Ru)-mediated 18F-deoxyfluorination method. [18F]CNY-05 exhibited preferable brain uptake, high specific binding, and slightly reversible pharmacokinetics within the PET scanning time window. PET imaging of [18F]CNY-05 in nonhuman primates (NHP) indicated brain permeability, metabolic stability, and safety. Moreover, autoradiography and PET studies of [18F]CNY-05 in the AD mouse model found a significantly decreased brain uptake compared to that in wild-type mice. Collectively, we have provided a novel 18F-radiolabeled σ1R PET probe, which enables visualizing brain σ1R in health and neurological diseases.

Assessing the Effect of Cold Plasma on the Softening of Postharvest Blueberries through Reactive Oxygen Species Metabolism Using Transcriptomic Analysis.

The postharvest softening and corresponding quality deterioration of blueberry fruits are crucial factors that hinder long-distance sales and long-term storage. Cold plasma (CP) is an effective technology to solve this, but the specific mechanism of delaying fruit softening remains to be revealed. Here, this study found that CP significantly improved blueberry hardness. Physiological analysis showed that CP regulated the dynamic balance of reactive oxygen species (ROS) to maintain hardness by increasing antioxidant content and antioxidant enzyme activity, resulting in a 12.1% decrease in the H2O2 content. Transcriptome analysis revealed that CP inhibited the expression of cell wall degradation-related genes such as the pectin hydrolase gene and cellulase gene, but up-regulated the genes of the ROS-scavenging system. In addition, the resistance genes in the MAPK signaling pathway were also activated by CP in response to fruit ripening and softening and exhibited positive response characteristics. These results indicate that CP can effectively regulate the physiological characteristics of blueberries at a genetic level and delay the softening process, which is of great significance to the storage of blueberries.

Engineering strategies and challenges of endolysin as an antibacterial agent against Gram-negative bacteria.

Bacteriophage endolysin is a novel antibacterial agent that has attracted much attention in the prevention and control of drug-resistant bacteria due to its unique mechanism of hydrolysing peptidoglycans. Although endolysin exhibits excellent bactericidal effects on Gram-positive bacteria, the presence of the outer membrane of Gram-negative bacteria makes it difficult to lyse them extracellularly, thus limiting their application field. To enhance the extracellular activity of endolysin and facilitate its crossing through the outer membrane of Gram-negative bacteria, researchers have adopted physical, chemical, and molecular methods. This review summarizes the characterization of endolysin targeting Gram-negative bacteria, strategies for endolysin modification, and the challenges and future of engineering endolysin against Gram-negative bacteria in clinical applications, to promote the application of endolysin in the prevention and control of Gram-negative bacteria.

Characterization of structural and functional properties of soybean 11S globulin during renaturation after denaturation induced by changes in pH.

BACKGROUND: This study explored the denaturation of 11S globulin, a protein known for its diverse functional properties in soy protein applications, at pH 3.0 and pH 10.0, followed by a gradual return to pH 7.0 to facilitate renaturation. It investigated the structural and functional changes during renaturation induced by a change in pH, revealing the stabilization mechanism of 11S globulin. RESULTS: The findings revealed that during pH adjustment to neutral, the denatured soybean 11S globulin - resulting from alkaline (pH 10.0) or acidic (pH 3.0) treatments - experienced a refolding of its extended tertiary structure to varying extents. The particle size and the proportions of α-helix and ß-sheet in the secondary structure aligned progressively with those of the natural-state protein. However, for the alkali-denatured 11S, the ß-sheet content decreased upon adjustment to neutral, whereas an increase was observed for the acid-denatured 11S. In terms of functional properties, after alkaline denaturation, the foaming capacity (FC) and emulsifying activity index (EAI) of 11S increased by 1.4 and 1.2 times, respectively, in comparison with its native state. The solubility, foamability, and emulsifiability of the alkali-denatured 11S gradually diminished during renaturation but remained superior to those of the native state. Conversely, these properties showed an initial decline, followed by an increase during renaturation triggered by pH neutralization. CONCLUSIONS: This research contributes to the enhancement of protein functionality, offering a theoretical foundation for the development of functional soy protein products and expanding their potential applications. © 2024 Society of Chemical Industry.

Distinct neural dynamics of the observed ostracism effect in decision-making under risk and ambiguity.

Observational ostracism, as a form of social exclusion, can significantly affect human behavior. However, the effects of observed ostracism on risky and ambiguous decision-making and the underlying neural mechanisms remain unclear. This event-related potential study investigated these issues by involving participants in a wheel-of- fortune task, considering observed ostracism and inclusion contexts. The results showed that the cue-P3 component was more enhanced during the choice phase for risky decisions than for ambiguous decisions in the observed inclusion contexts but not in the observed ostracism contexts. During the outcome evaluation phase, feedback-related negativity amplitudes following both risky and ambiguous decisions were higher in the no-gain condition than in the gain condition in the observed inclusion context. In contrast, this effect was only observed following risky decisions in the observed ostracism context. The feedback-P3 component did not exhibit an observed ostracism effect in risky and ambiguous decision-making tasks. Risk levels further modulated the cue-P3 and feedback-related negativity components, while ambiguity levels further modulated the feedback-P3 components. These findings demonstrate a neural dissociation between risk and ambiguity decision-making during observed ostracism that unfolds from the choice phase to the outcome evaluation phase.