Novel thawing method of ultrasound-assisted slightly basic electrolyzed water improves the processing quality of frozen shrimp compared with traditional thawing approaches.

Thawing is the primary step in handling frozen aquatic products, which directly determines their end-product quality. This study firstly constructed a novel thawing method of ultrasound-assisted slightly basic electrolyzed water (UST), and its influences on the physicochemical and histological properties of shrimp, as well as the structural of myofibrillar proteins (MPs) in shrimp were evaluated. Results indicated that the UST treatment greatly reduced 48.9 % thawing time of frozen shrimp compared to traditional thawing approaches. Meanwhile, the UST effectively decreased the generation of malondialdehyde (MDA), total volatile basic nitrogen (TVB-N), and carbonyl compounds in the thawed shrimps. In addition, it significantly preserved the elasticity and integrity of muscle fiber. Notably, the UST reduced the damage of thawing to the spatial structures of MPs, thereby greatly keeping the stability of protein. All these favorable changes maintained the water holding capacity (WHC) and quality of shrimp. Therefore, the UST is a promising non-thermal thawing technology for aquatic products.

Luminol-Eu3+-Gd3+-functionalized mesoporous silica for ultrasensitive detection of tetracycline antibiotics and smartphone-assisted sensing analysis.

An organic-inorganic hybrid nanoprobe, namely LML-D-SBA@Eu3+-Gd3+, was constructed, with SBA-15 acting as the carrier material, and luminol and Eu3+ acting as fluorescence channels to achieve ratiometric signals that eliminate external interference (accurate detection). Gd3+ was used as a sensitizer to amplify the red emission of Eu3+ (ultrasensitive detection). In TCs detection, the luminol emission at 428 nm was quenched due to the photoinduced electron transfer mechanism, and the Eu3+ emission at 617 nm was sensitized due to the synergistic energy transfer from TCs and Gd3+ to Eu3+. The fluorescence intensity at 617 and 428 nm showed ratiometric changes as indicated by notable color changes from blue to red. The detection limits for TC and OTC were 0.21 and 0.08 ng/mL, respectively. To realize a facile, rapid, and cost-effective detection, we constructed a portable intelligent sensing platform based on smartphones, and it demonstrated great potential for on-site detection of TCs.

A method for extracting corneal reflection images from multiple eye images.

The incident light reflected from the cornea is rich in information about the human surroundings, and these reflected rays are imaged by the camera, which can be used for research on human consciousness and gaze analysis, and produce certain help in the fields of psychology, human computer interaction and disease diagnosis. However, limited by the low corneal reflection ability, when a high-definition camera captures corneal reflecting rays, a large amount of color and texture interference from the iris can seriously contaminate the corneal reflection images, resulting in low usability and ubiquity of corneal reflection images. In this paper, we propose a corneal reflection image extraction method with multiple eye images as input. We align the iris regions of multiple eye images with the help of iris localization method, and by comparing multiple iris regions, we obtain the complementary iris regions, so that the iris interference in the corneal reflection region can be stripped completely. A large number of experiments have demonstrated that our work can effectively mitigate iris interference and effectively improve the quality of corneal reflection images.

ClickSAM: Fine-tuning Segment Anything Model using click prompts for ultrasound image segmentation.

The newly released Segment Anything Model (SAM) is a popular tool used in image processing due to its superior segmentation accuracy, variety of input prompts, training capabilities, and efficient model design. However, its current model is trained on a diverse dataset not tailored to medical images, particularly ultrasound images. Ultrasound images tend to have a lot of noise, making it difficult to segment out important structures. In this project, we developed ClickSAM, which fine-tunes the Segment Anything Model using click prompts for ultrasound images. ClickSAM has two stages of training: the first stage is trained on single-click prompts centered in the ground-truth contours, and the second stage focuses on improving the model performance through additional positive and negative click prompts. By comparing the first stage's predictions to the ground-truth masks, true positive, false positive, and false negative segments are calculated. Positive clicks are generated using the true positive and false negative segments, and negative clicks are generated using the false positive segments. The Centroidal Voronoi Tessellation algorithm is then employed to collect positive and negative click prompts in each segment that are used to enhance the model performance during the second stage of training. With click-train methods, ClickSAM exhibits superior performance compared to other existing models for ultrasound image segmentation.

Registration of hyperspectral images and mass spectrometry data for the correlation of tissue optical spectra and molecular profiles.

Hyperspectral imaging (HSI) is a label-free imaging modality that is emerging for non-invasive detection of various diseases including cancers. HSI provides high-resolution spatial images where each pixel has a spectral curve with numerous wavelength bands from the visible to infrared ranges. The rich spatial and spectral information can be used to discriminate various types of tissues and pathophysiological conditions. However, it can be difficult to explain spectral data with respect to the underline cellular and molecular mechanism. In this study, we developed an approach that registers hyperspectral images and mass spectrometry (MS) data where MS provides tissue molecular profiles. Human prostate tissues that were obtained after prostatectomy were used in the experiments. The whole prostate was first sliced every six mm. A customized hyperspectral surgical microscope was used to acquire HSI data from the sliced tissue. For MS data analysis, the sliced tissue of the prostate was divided into 51 small regions and then processed separately for each region. The immediately adjacent tissue was sliced and processed histologically for H&E staining. The MS molecular profiles were correlated with the hyperspectral images in this study.

Interferon-induced MXB protein restricts vimentin-dependent viral infection.

Type I interferon (IFN) inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins. As an IFN-induced protein, myxovirus resistance B (MXB) protein was reported to inhibit multiple highly pathogenic human viruses. It remains to be determined whether MXB employs a common mechanism to restrict different viruses. Here, we find that IFN alters the subcellular localization of hundreds of host proteins, and this IFN effect is partially lost upon MXB depletion. The results of our mechanistic study reveal that MXB recognizes vimentin (VIM) and recruits protein kinase B (AKT) to phosphorylate VIM at amino acid S38, which leads to reorganization of the VIM network and impairment of intracellular trafficking of virus protein complexes, hence causing a restriction of virus infection. These results highlight a new function of MXB in modulating VIM-mediated trafficking, which may lead towards a novel broad-spectrum antiviral strategy to control a large group of viruses that depend on VIM for successful replication.

Discovery and Optimization of Tetrahydroisoquinoline Derivatives To Enhance Lysosome Biogenesis as Preclinical Candidates for the Treatment of Alzheimer's Disease.

More than 55 million individuals are suffering from Alzheimer's disease (AD), while the effective therapeutic strategies remain elusive. Our previous study identified a lysosome-enhancing lead compound LH2-051 with a tetrahydroisoquinoline scaffold through a novel dopamine transporter-cyclin-dependent kinase 9-transcription factor EB (DAT-CDK9-TFEB) regulation mechanism to promote TFEB activation and lysosome biogenesis. Here, we launched a comprehensive structure-activity relationship study for LH2-051, and 47 new derivatives were designed and synthesized, in which several compounds exhibited remarkable lysosome-enhancing activities. Notably, compounds 37 and 45 exhibited more favorable TFEB activation and lysosome biogenesis capabilities, good safety profiles, and excellent pharmacokinetic profiles with high brain penetration. Further investigations demonstrated that both compounds significantly enhance the clearance of Aß aggregates and ameliorate the impairment of learning, memory, and cognition in APP/PS1 mice. Overall, these results indicated that compounds 37 and 45 are promising preclinical drug candidates for the treatment of AD.

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.

The accumulation of cadmium and lead in wheat grains is primarily determined by the soil-reducible cadmium level during wheat tillering.

The significant increase in cadmium (Cd) and lead (Pb) pollution in agricultural soil has greatly heightened environmental contamination issues and the risk of human diseases. However, the mechanisms underlying the transformation of Cd and Pb in soil as well as the influencing factors during their accumulation in crop grains remain unclear. Based on the analysis of the distribution trend of Cd and Pb in soil during the growth and development stages of wheat (tillering, filling, and maturity) in alkaline heavy metal-polluted farmland in northern China, this study investigated the response mechanism of soil heavy metal form transformation to soil physicochemical properties, and elucidated the main determining periods and influencing factors for Cd and Pb enrichment in wheat grains. The results showed that an increase in CEC and SOM levels, along with a decrease in pH level, contributed to enhancing the bioavailability of Cd in the soil. This effect was particularly evident during the tillering stage and grain filling stage of wheat. Nevertheless, the effects of soil physicochemical properties on bioavailable Pb was opposite to that on bioavailable Cd. The enrichment of Cd and Pb in grain was significantly influenced by soil pH (r = -0.786, p < 0.01), SOM (r = 0.807, p < 0.01), K (r = -0.730, p < 0.01), AK (r = 0.474, p=0.019), and AP (r = -0.487, p = 0.016). The reducible form of Cd in soil during the wheat tillering stage was identified as the primary factor contributing to the accumulation of Cd and Pb in wheat grains, with a significant contribution rate of 84.5%. This study provides a greater scientific evidence for the management and risk control of heavy metal pollution in alkaline farmland.

Obinutuzumab in untreated primary membranous nephropathy: An observational case series.

BACKGROUND: As an initial treatment for primary membranous nephropathy (PMN), there remains a significant proportion of patients for whom rituximab is not fully effective. Here, we aimed to assess the effectiveness and safety of obinutuzumab as initial treatment in patients with PMN. METHODS: In this observational case series, patients diagnosed with PMN and treated with obinutuzumab as initial treatment were included. Treatment response was assessed by 24-h urine total protein (24 h UTP) and serum albumin, and immunologic remission was assessed by phospholipase A2 receptor (PLA2R) antibodies. RESULTS: Twelve patients with PMN receiving obinutuzumab as initial treatment were included. Over 6 months, a statistically significant reduction in 24 h UTP levels (p = 0.003) and an increase in serum albumin levels were observed (p < 0.001). By the 6-month follow-up, two patients (16.7%) achieved complete remission, eight (66.6%) reached partial remission, and two (16.7%) showed no remission. Immunological remission was observed in 44.4% of evaluable patients (n = 9) after 3 months, increasing to 100% (6/6) at 6 months. Except for cases 1, 2, and 3, the total B cell counts in the remaining patients fell to less than 5 cells/µL before the administration of the second dose of obinutuzumab, including seven patients with counts as low as 0 cells/µL. Mild to moderate treatment-related adverse events (TRAEs) were reported in 58.3% (7/12) of the patients. No serious TRAEs were reported. CONCLUSIONS: Obinutuzumab demonstrates promising potential as an initial treatment for PMN, with good effectiveness and a manageable safety profile. Further large-scale prospective studies are needed to confirm these findings.

Resveratrol and piceid enhance efferocytosis by increasing the secretion of MFG-E8 in human THP-1 macrophages.

The process of apoptotic cell clearance by phagocytes, known as efferocytosis, plays an essential role in maintaining homeostasis. Defects in efferocytosis can lead to inflammatory diseases such as atherosclerosis and autoimmune disorders. Therefore, the maintenance and promotion of efferocytosis are considered crucial for preventing these diseases. In this study, we observed that resveratrol, a representative functional food ingredient, and its glycoside, piceid, promoted efferocytosis in both human THP-1 macrophages differentiated with phorbol 12-myristate 13-acetate and peritoneal macrophages from thioglycolate-elicited mice. Resveratrol and piceid significantly increased mRNA expression and protein secretion of MFG-E8 in THP-1 macrophages. Furthermore, the activation of efferocytosis and the increment in MFG-E8 protein secretion caused by resveratrol or piceid treatment were canceled by MFG-E8 knockdown in THP-1 macrophages. In conclusion, we have demonstrated for the first time that resveratrol and piceid promote efferocytosis through the upregulation of MFG-E8 excretion in human THP-1 macrophages.

Harnessing three-dimensional porous chitosan microsphere embedded with adipose-derived stem cells to promote nerve regeneration.

BACKGROUND: Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. METHODS: In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. RESULTS: Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. CONCLUSIONS: The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair.

Advanced nerve regeneration enabled by neural conformal electronic stimulators enhancing mitochondrial transport.

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

A modified low-priming cardiopulmonary bypass system in patients undergoing cardiac surgery with medium risk of transfusion: A randomized controlled trial.

Objectives: The FUWAI-SAVE system is a modified low-priming cardiopulmonary bypass (CPB) system. The study aimed to explore whether the FUWAI-SAVE system can reduce the perioperative blood transfusion and its impact on other postoperative complications during cardiac surgery. Metohds: This study was a single-center, single-blind, randomized controlled trial, registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2100050488). Adult patients undergoing cardiac surgery with CPB and intermediate risk for transfusion risk stratification were randomly assigned to an intervention group (FUWAI-SAVE group) or a control group (conventional group). The primary endpoint of the study was the peri-CPB red blood cell transfusion (RBC) rate. The secondary endpoints included the transfusion rate of other blood products, the amount of blood products transfused, the incidence of major complications, in-hospital mortality, and others. Results: 360 patients were randomized from December 9, 2021, to January 30, 2023. The rate of the primary endpoint was significantly lower in the FUWAI-SAVE group compared to the control group [ OR (95%CI): 0.649 (0.424-0.994)]. Meanwhile, the amount of RBC transfusion during the peri-CPB period was significantly lower in the FUWAI-SAVE group compared to the control group, with a mean difference of -0.626 (-1.176 to -0.076) units. The occurrence rate of major complications did not differ significantly between the two groups. Conclusions: Among adult patients undergoing cardiac surgery with CPB, the application of the FUWAI-SAVE system significantly reduced RBC transfusion rate and amount. The FUWAI-SAVE system can be considered an important component of comprehensive blood management strategies in cardiac surgery.

Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation.

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.

Callus-specific CRISPR/Cas9 system to increase heritable gene mutations in maize.

MAIN CONCLUSION: A callus-specific CRISPR/Cas9 (CSC) system with Cas9 gene driven by the promoters of ZmCTA1 and ZmPLTP reduces somatic mutations and improves the production of heritable mutations in maize. The CRISPR/Cas9 system, due to its editing accuracy, provides an excellent tool for crop genetic breeding. Nevertheless, the traditional design utilizing CRISPR/Cas9 with ubiquitous expression leads to an abundance of somatic mutations, thereby complicating the detection of heritable mutations. We constructed a callus-specific CRISPR/Cas9 (CSC) system using callus-specific promoters of maize Chitinase A1 and Phospholipid transferase protein (pZmCTA1 and pZmPLTP) to drive Cas9 expression, and the target gene chosen for this study was the bZIP transcription factor Opaque2 (O2). The CRISPR/Cas9 system driven by the maize Ubiquitin promoter (pZmUbi) was employed as a comparative control. Editing efficiency analysis based on high-throughput tracking of mutations (Hi-TOM) showed that the CSC systems generated more target gene mutations than the ubiquitously expressed CRISPR/Cas9 (UC) system in calli. Transgenic plants were generated for the CSC and UC systems. We found that the CSC systems generated fewer target gene mutations than the UC system in the T0 seedlings but reduced the influence of somatic mutations. Nearly 100% of mutations in the T1 generation generated by the CSC systems were derived from the T0 plants. Only 6.3-16.7% of T1 mutations generated by the UC system were from the T0 generation. Our results demonstrated that the CSC system consistently produced more stable, heritable mutants in the subsequent generation, suggesting its potential application across various crops to facilitate the genetic breeding of desired mutations.

SR9009 attenuates inflammation-related NPMSC pyroptosis and IVDD through NR1D1/NLRP3/IL-1ß pathway.

Intervertebral disc is a highly rhythmical tissue. As a key factor linking biorhythm and inflammatory response, the shielding effect of NR1D1 in the process of intervertebral disc degeneration remains unclear. Here, we first confirmed that NR1D1 in the nucleus pulposus tissue presents periodic rhythmic changes and decreases in expression with intervertebral disc degeneration. Second, when NR1D1 was activated by SR9009 in vitro, NLRP3 inflammasome assembly and IL-1ß production were inhibited, while ECM synthesis was increased. Finally, the vivo experiments further confirmed that the activation of NR1D1 can delay the process of disc degeneration to a certain extent. Mechanistically, we demonstrate that NR1D1 can bind to IL-1ß and NLRP3 promoters, and that the NR1D1/NLRP3/IL-1ß pathway is involved in this process. Our results demonstrate that the activation of NR1D1 can effectively reduce IL-1ß secretion, alleviate LPS-induced NPMSC pyroptosis, and protect ECM degeneration.

Genomic evidence for evolutionary history and local adaptation of two endemic apricots: Prunus hongpingensis and P. zhengheensis.

Apricot, belonging to the Armeniaca section of Rosaceae, is one of the economically important crop fruits that has been extensively cultivated. The natural wild apricots offer valuable genetic resources for crop improvement. However, some of them are endemic, with small populations, and are even at risk of extinction. In this study we unveil chromosome-level genome assemblies for two southern China endemic apricots, Prunus hongpingensis (PHP) and P. zhengheensis (PZH). We also characterize their evolutionary history and the genomic basis of their local adaptation using whole-genome resequencing data. Our findings reveal that PHP and PZH are closely related to Prunus armeniaca and form a distinct lineage. Both species experienced a decline in effective population size following the Last Glacial Maximum (LGM), which likely contributed to their current small population sizes. Despite the observed decrease in genetic diversity and heterozygosity, we do not observe an increased accumulation of deleterious mutations in these two endemic apricots. This is likely due to the combined effects of a low inbreeding coefficient and strong purifying selection. Furthermore, we identify a set of genes that have undergone positive selection and are associated with local environmental adaptation in PHP and PZH, respectively. These candidate genes can serve as valuable genetic resources for targeted breeding and improvement of cultivated apricots. Overall, our study not only enriches our comprehension of the evolutionary history of apricot species but also offers crucial insights for the conservation and future breeding of other endemic species amidst rapid climate changes.