Navß2 Intracellular Fragments Contribute to Aß1-42-Induced Cognitive Impairment and Synaptic Deficit Through Transcriptional Suppression of BDNF.

A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aß), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aß pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navß2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aß1-42 and AD mice, the possible effects and potential mechanisms induced by Navß2. The results reveal that Aß1-42 induces remarkable increases in Navß2 intracellular domain (Navß2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navß2-ICD further enhances these effects induced by Aß1-42, while interfering the generation of Navß2-ICD and/or complementing BDNF neutralize the Navß2-ICD-conducted effects. Luciferase reporter assay verifies that Navß2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navß2 induced by Aß1-42-associated AD pathology leads to intracellular Navß2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navß2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD.

Engineering Gluconbacter oxydans with efficient co-utilization of glucose and sorbitol for one-step biosynthesis of 2-keto-L-gulonic.

As the highest-demand vitamin, the development of a one-step vitamin C synthesis process has been slow for a long time. In previous research, a Gluconobacter oxydans strain (GKLG9) was constructed that can directly synthesize 2-keto-L-gulonic acid (2-KLG) from glucose, but carbon source utilization remained low. Therefore, this study first identified the gene 4kas (4-keto-D-arabate synthase) to reduce the loss of extracellular carbon and inhibit the browning of fermentation broth. Then, promoter engineering was conducted to enhance the intracellular glucose transport pathway and concentrate intracellular glucose metabolism on the pentose phosphate pathway to provide more reducing power. Finally, by introducing the D-sorbitol pathway, the titer of 2-KLG was increased to 38.6 g/L within 60 h in a 5-L bioreactor, with a glucose-to-2-KLG conversion rate of about 46 %. This study is an important step in the development of single-bacterial one-step fermentation to produce 2-KLG.

Screening of ent-copalyl diphosphate synthase and metabolic engineering to achieve de novo biosynthesis of ent-copalol in Saccharomyces cerevisiae.

The diterpene ent-copalol is an important precursor to the synthesis of andrographolide and is found only in green chiretta (Andrographis paniculata). De novo biosynthesis of ent-copalol has not been reported, because the catalytic activity of ent-copalyl diphosphate synthase (CPS) is very low in microorganisms. In order to achieve the biosynthesis of ent-copalol, Saccharomyces cerevisiae was selected as the chassis strain, because its endogenous mevalonate pathway and dephosphorylases could provide natural promotion for the synthesis of ent-copalol. The strain capable of synthesizing diterpene geranylgeranyl pyrophosphate was constructed by strengthening the mevalonate pathway genes and weakening the competing pathway. Five full-length ApCPSs were screened by transcriptome sequencing of A. paniculata and ApCPS2 had the best activity and produced ent-CPP exclusively. The peak area of ent-copalol was increased after the ApCPS2 saturation mutation and its configuration was determined by NMR and ESI-MS detection. By appropriately optimizing acetyl-CoA supply and fusion-expressing key enzymes, 35.6 mg/L ent-copalol was generated. In this study, de novo biosynthesis and identification of ent-copalol were achieved and the highest titer ever reported. It provides a platform strain for the further pathway analysis of andrographolide and derivatives and provides a reference for the synthesis of other pharmaceutical intermediates.

BinsFormer: Revisiting Adaptive Bins for Monocular Depth Estimation.

Monocular depth estimation (MDE) is a fundamental task in computer vision and has drawn increasing attention. Recently, some methods reformulate it as a classification-regression task to boost the model performance, where continuous depth is estimated via a linear combination of predicted probability distributions and discrete bins. In this paper, we present a novel framework called BinsFormer, tailored for the classification-regression-based depth estimation. It mainly focuses on two crucial components in the specific task: 1) proper generation of adaptive bins; and 2) sufficient interaction between probability distribution and bins predictions. To specify, we employ a Transformer decoder to generate bins, novelly viewing it as a direct set-to-set prediction problem. We further integrate a multi-scale decoder structure to achieve a comprehensive understanding of spatial geometry information and estimate depth maps in a coarse-to-fine manner. Moreover, an extra scene understanding query is proposed to improve the estimation accuracy, which turns out that models can implicitly learn useful information from the auxiliary environment classification task. Extensive experiments on the KITTI, NYU, and SUN RGB-D datasets demonstrate that BinsFormer surpasses state-of-the-art MDE methods with prominent margins. Code and pretrained models are made publicly available at https://github.com/zhyever/ Monocular-Depth-Estimation-Toolbox/tree/main/configs/ binsformer.

Influence of different penetrating cryoprotectants and egg yolk level on the post-thaw quality of sperm.

Objective: The Hu sheep is a renowned breed known for its high reproductive rate. It is in estrus all year round, and its breeding population is gradually expanding. However, the current techniques for cryopreserving semen have limited effectiveness, which hinders the continuous development of this species. The purpose of this study is to explore the effects of different penetrating cryoprotectants (CPAs) and egg yolk (EY) concentrations on the cryopreservation of Hu ram semen to determine the most effective combination. Methods: In this study, the effects of glycerol (GLY), ethylene glycol (EG), dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), different proportions of GLY and EG, EY on sperm quality after thawing were investigated by detecting sperm total motility (TM), progressive motility (PM), straight-line velocity (VSL), curvilinear velocity (VCL), average path velocity (VAP), amplitude of lateral head displacement (ALH), wobble movement coefficient (WOB), average motion degree (MAD), functional integrity (plasma membrane integrity, acrosome integrity) and reactive oxygen species (ROS) level. Results: When GLY and EG were added together, compared to other concentration groups, 6% GLY significantly (p < 0.05) increased TM, PM, plasma membrane integrity, and acrosome integrity of thawed sperm. Additionally, it significantly (p < 0.05) decreased the ROS level of sperm. In this study, the TM, PM and membrane integrity of the 6% EG were significantly (p < 0.05) higher than those of the control, 1% GLY+5% EG and 6% GLY+6% EG groups. Compared to other concentration groups, 20% EY significantly (p < 0.05) improved the TM, PM, and plasma membrane integrity of thawed sperm. However, the integrity of the acrosome increased with the higher concentration of EY. Conclusion: In conclusion, the post-thawed Hu ram semen diluted with a diluent containing 6% GLY and 20% EY exhibited higher quality compared to the other groups.

Effects of Different Diluents and Freezing Methods on Cryopreservation of Hu Ram Semen.

The purpose of this study was to investigate the effects of different diluents and freezing methods on the quality of thawed sperm after cryopreservation and find an inexpensive and practical method for freezing Hu ram semen for use in inseminations under farm conditions. Ejaculates were collected from five Hu rams. In experiment I, ejaculates were diluted with eight different freezing diluents (basic diluents A, B, C, D, E, F, G, and H). After dilution and cooling, the samples were loaded into 0.25 mL straws and frozen using the liquid nitrogen fumigation method. In experiment II, diluent C was used as the basic diluent and the semen was frozen using liquid nitrogen fumigation and two program-controlled cooling methods. For analysis, frozen samples were evaluated in terms of motility parameters (total motility (TM), progressive motility (PM)), biokinetic characteristics (straight-line velocity (VSL), average path velocity (VAP), curvilinear velocity (VCL), amplitude of lateral head displacement (ALH), wobble movement coefficient (WOB), average motion degree (MAD)), reactive oxygen species (ROS) level, and membrane and acrosome integrity. In experiment I, diluent C had higher TM, PM, and acrosome and membrane integrity and lower ROS compared to other extenders (p < 0.05) except diluent A. Diluent C exhibited higher (p < 0.05) VCL, VAP, ALH, WOB, and MAD compared to diluents B, D, E, and F. In experiment II, TM and all biokinetic characteristics did not show significant differences (p > 0.05) amongst the three freezing methods. Liquid nitrogen fumigation resulted in higher (p < 0.05) PM, membrane integrity, acrosome integrity, and lower ROS level compared to the program. In conclusion, the thawed semen diluted with diluent C had higher quality compared to other diluents. The liquid nitrogen fumigation demonstrated superior semen cryopreservation effects compared to the program-controlled cooling method using diluent C.

Individualized Structural Perturbations on Normative Brain Connectome Restrict Deep Brain Stimulation Outcomes in Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) respond to deep brain stimulation (DBS) variably. However, how brain substrates restrict DBS outcomes remains unclear. OBJECTIVE: In this article, we aim to identify prognostic brain signatures for explaining the response variability. METHODS: We retrospectively investigated a cohort of patients with PD (n = 141) between 2017 and 2022, and defined DBS outcomes as the improvement ratio of clinical motor scores. We used a deviation index to quantify individual perturbations on a reference structural covariance network acquired with preoperative T1-weighted magnetic resonance imaging. The neurobiological perturbations of patients were represented as z scored indices based on the chronological perturbations measured on a group of normal aging adults. RESULTS: After applying stringent statistical tests (z > 2.5) and correcting for false discoveries (P < 0.01), we found that accelerated deviations mainly affected the prefrontal cortex, motor strip, limbic system, and cerebellum in PD. Particularly, a negative network within the accelerated deviations, expressed as "more preoperative deviations, less postoperative improvements," could predict DBS outcomes (mean absolute error = 0.09, R2 = 0.15). Moreover, a fusion of personal brain predictors and medical responses significantly improved traditional evaluations of DBS outcomes. Notably, the most important brain predictor, a pathway connecting the cognitive unit (prefrontal cortex) and motor control unit (cerebellum and motor strip), partially mediates DBS outcomes with the age at surgery. CONCLUSIONS: Our findings suggest that individual structural perturbations on the cognitive motor control circuit are critical for modulating DBS outcomes. Interventions toward the circuit have the potential for additional clinical improvements. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Use of Intravoxel Incoherent Motion Diffusion-Weighted Imaging to Assess Mesenchymal Stromal Cells Promoting Liver Regeneration in a Rat Model.

RATIONALE AND OBJECTIVES: Mesenchymal stem cells (MSCs) have the potential to promote liver regeneration, but the process is unclear. This study aims to explore the therapeutic effects and dynamic processes of MSCs in liver regeneration through intravoxel incoherent motion (IVIM) imaging. ANIMAL MODEL: 70 adult Sprague-Dawley rats were randomly divided into either the control or MSC group (n = 35/group). All rats received a partial hepatectomy (PH) with the left lateral and middle lobes removed. Each group was divided into seven subgroups: pre-PH and 1, 2, 3, 5, 7, and 14 days post-PH (n = 5 rats/subgroup). Magnetic resonance imaging (MRI) was performed before obtaining pathological specimens at each time point on postoperative days 1, 2, 3, 5, 7, and 14. The MRI parameters for the pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF) were calculated. Correlation analysis was conducted for the biochemical markers (alanine transaminase [ALT], aspartate transaminase [AST], and total bilirubin [TBIL]), histopathological findings (hepatocyte size and Ki-67 proliferation index), liver volume (LV) and liver regeneration rate (LLR). RESULTS: Liver D, D* , and PF differed significantly between the control and MSC groups at all time points (all P < 0.05). After PH, the D increased, then decreased, and the D* and PF decreased, then increased in both groups. The hepatocyte Ki-67 proliferation index of the MSC group was lower on day 2 post-PH, but higher on days 3 and 5 post-PH than that of the control group. Starting from day 3 post-PH, both the LV and LLR in the MSC group were greater than those in the control group (all P < 0.05). Hepatocytes were larger in the MSC group than in the control group on days 2 and 7 post-PH. In the MSC group, the D, D* , and PF were correlated with the AST levels, Ki-67 index and hepatocyte size (|r|=0.35-0.71; P < 0.05). In the control group, the D and D* were correlated with ALT levels, AST levels, Ki-67 index, LLR, LV, and hepatocyte size (|r|=0.34-0.95; P < 0.05). CONCLUSION: Bone marrow MSC therapy can promote hepatocyte hypertrophy and prolong liver proliferation post-PH. IVIM parameters allow non-invasively evaluating the efficacy of MSCs in promoting LR.

Dynamic causal modeling analysis reveals the modulation of motor cortex and integration in superior temporal gyrus during multisensory speech perception.

The processing of speech information from various sensory modalities is crucial for human communication. Both left posterior superior temporal gyrus (pSTG) and motor cortex importantly involve in the multisensory speech perception. However, the dynamic integration of primary sensory regions to pSTG and the motor cortex remain unclear. Here, we implemented a behavioral experiment of classical McGurk effect paradigm and acquired the task functional magnetic resonance imaging (fMRI) data during synchronized audiovisual syllabic perception from 63 normal adults. We conducted dynamic causal modeling (DCM) analysis to explore the cross-modal interactions among the left pSTG, left precentral gyrus (PrG), left middle superior temporal gyrus (mSTG), and left fusiform gyrus (FuG). Bayesian model selection favored a winning model that included modulations of connections to PrG (mSTG → PrG, FuG → PrG), from PrG (PrG → mSTG, PrG → FuG), and to pSTG (mSTG → pSTG, FuG → pSTG). Moreover, the coupling strength of the above connections correlated with behavioral McGurk susceptibility. In addition, significant differences were found in the coupling strength of these connections between strong and weak McGurk perceivers. Strong perceivers modulated less inhibitory visual influence, allowed less excitatory auditory information flowing into PrG, but integrated more audiovisual information in pSTG. Taken together, our findings show that the PrG and pSTG interact dynamically with primary cortices during audiovisual speech, and support the motor cortex plays a specifically functional role in modulating the gain and salience between auditory and visual modalities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09945-z.

Bisgermylene-Stabilized Stannylone: Catalytic Reduction of Nitrous Oxide and Nitro Compounds via Element-Ligand Cooperativity.

This study describes the synthesis, structural characterization, and catalytic application of a bis(germylene)-stabilized stannylone (2). The reduction of digermylated stannylene (1) with 2.2 equiv of potassium graphite (KC8) leads to the formation of stannylone 2 as a green solid in 78% yield. Computational studies showed that stannylone 2 possesses a formal Sn(0) center and a delocalized 3-c-2-e π-bond in the Ge2Sn core, which arises from back-donation of the p-type lone pair electrons on the Sn atom to the vacant orbitals of the Ge atoms. Stannylone 2 can serve as an efficient precatalyst for the selective reduction of nitrous oxide (N2O) and nitroarenes (ArNO2) with the formation of dinitrogen (N2) and hydrazines (ArNH-NHAr), respectively. Exposure of 2 with N2O (1 atm) resulted in the insertion of two oxygen atoms into the Ge-Ge and Ge-Sn bonds, yielding the germyl(oxyl)stannylene (3). Moreover, the stoichiometric reaction of 2 with 1-chloro-4-nitrobenzene afforded an amido(oxyl)stannylene (4) through the complete scission of the N-O bonds of the nitroarene. Stannylenes 3 and 4 serve as catalytically active species for the catalytic reduction of nitrous oxide and nitroarenes, respectively. Mechanistic studies reveal that the cooperation of the low-valent Ge and Sn centers allows for multiple electron transfers to cleave the N-O bonds of N2O and ArNO2. This approach presents a new strategy for catalyzing the deoxygenation of N2O and ArNO2 using a zerovalent tin compound.

Gut microbiota is necessary for pair-housing to protect against post-stroke depression in mice.

The goal of this study is to investigate the role of microbiota-gut-brain axis involved in the protective effect of pair-housing on post-stroke depression (PSD). PSD model was induced by occluding the middle cerebral artery (MCAO) plus restraint stress for four weeks. At three days after MCAO, the mice were restrained 2 h per day. For pair-housing (PH), each mouse was pair housed with a healthy isosexual cohabitor for four weeks. While in the other PH group, their drinking water was replaced with antibiotic water. On day 35 to day 40, anxiety- and depression-like behaviors (sucrose consumption, open field test, forced swim test, and tail-suspension test) were conducted. Results showed pair-housed mice had better performance on anxiety- and depression-like behaviors than the PSD mice, and the richness and diversity of intestinal flora were also improved. However, drinking antibiotic water reversed the effects of pair-housing. Furthermore, pair-housing had an obvious improvement in gut barrier disorder and inflammation caused by PSD. Particularly, they showed significant decreases in CD8 lymphocytes and mRNA levels of pro-inflammatory cytokines (TNF-a, IL-1ß and IL-6), while IL-10 mRNA was upregulated. In addition, pair-housing significantly reduced activated microglia and increased Nissl's body in the hippocampus of PSD mice. However, all these improvements were worse in the pair-housed mice administrated with antibiotic water. We conclude that pair-housing significantly improves PSD in association with enhanced functions of microbiota-gut-brain axis, and homeostasis of gut microbiota is indispensable for the protective effect of pair-housing on PSD.

[Impact of primary duodenogastric reflux and Helicobacter pylori infection on gastritis and antibiotic resistance in children]. / å„¿ç«¥åŽŸå‘æ€§åäºŒæŒ‡è‚ èƒƒåæµä¸Žå¹½é—¨èžºæ†èŒæ„ŸæŸ“å¯¹èƒƒç‚Žå’ŒæŠ—ç”Ÿç´ è€è¯æ€§çš„å½±å“.

OBJECTIVES: To investigate the risk factors for Helicobacter pylori (HP) infection in children with primary duodenogastric reflux (DGR) and its impact on gastritis and antibioticresistance. METHODS: A retrospective analysis was performed on the clinical data of 2 190 children who underwent upper gastrointestinal endoscopy in Wuxi Children's Hospital from January 2019 to February 2022, among whom 308 children were diagnosed with primary DGR. According to the presence or absence of HP infection, the children were classified to HP infection group (53 children) and non-HP infection group (255 children). The risk factors for HP infection and its impact on the incidence rate and severity of gastritis were analyzed. According to the presence or absence of primary DGR, 331 children with HP infection were classified to primary DGR group (29 children) and non-primary DGR group (302 children), and then the impact of primary DGR with HP infection on antibiotic resistance was analyzed. RESULTS: The HP infection group had a significantly higher age than the non-HP infection group (P<0.05), and there was a significant difference in the age distribution between the two groups (P<0.05), while there were no significant differences in the incidence rate and severity of gastritis between the two groups (P>0.05). The multivariate logistic regression analysis showed that older age was a risk factor for HP infection in children with DGR (P<0.05). Drug sensitivity test showed that there were no significant differences in the single and combined resistance rates of metronidazole, clarithromycin, and levofloxacin between the primary DGR group and the non-primary DGR group (P>0.05). CONCLUSIONS: Older age is closely associated with HP infection in children with DGR. Primary DGR with HP infection has no significant impact on gastritis and antibiotic resistance in children.

Biomarker-triggered, spatiotemporal controlled DNA nanodevice simultaneous assembly and disassembly.

Despite many advances in the use of DNA nanodevices as assembly or disassembly modules to build various complex structures, the simultaneous assembly and disassembly of DNA structures in living cells remains a challenge. In this study, we present a modular engineering approach for assembling and disassembling DNA nanodevices in response to endogenous biomarkers. As a result of pairwise prehybridization of original DNA strands, the DNA nanodevice is initially inert. In an effort to bind one of the paired strands and release its complement, nucleolin competes. Assembly of the DNA nanodevice is initiated when the released complement binds to it, and disassembly is initiated when APE1 shears the assembled binding site of the DNA nanodevice. Spatial-temporal logic control is achieved through our approach during the assembly and disassembly of DNA nanodevices. Furthermore, by means of this assembly and disassembly procedure, the sequential detection and imaging of two tumor markers can be achieved, thereby effectively reducing false-positive signal results and accelerating the detection time. This study emphasizes the simultaneous assembly and disassembly of DNA nanodevices controlled by biomarkers in a simple and versatile manner; it has the potential to expand the application scope of DNA nanotechnology and offers an idea for the implementation of precision medicine testing.

Luminescence and Energy Transfer Properties of Color-Tunable Dy3+, Eu3+ co-Activated NaGdSiO4 Phosphor for WLED with Great Thermo-Stability.

A series of NaGd1-x-ySiO4: y Dy3+-x Eu3+ phosphors were synthesized by a high-temperature solid-phase method. The optimal doping ion concentration of Dy3+ ions for this phosphor was determined to be 1 % from the emission spectra. The energy transfer between Dy3+ and Eu3+ ions at 351 nm was investigated by photoluminescence spectra and fluorescence decay curves. At the excitation wavelengths of 275 nm, 351 nm, 366 nm, and 394 nm, a change from yellow to white to red light can be realized by adjusting the doping concentration of Eu/Dy ions. Particularly, by testing the temperature-dependent fluorescence spectrum of the phosphor, it can be found that the luminous intensity of the phosphor is as high as 96 % when 394 nm excitation is employed at 413 K. It was the maximum at this temperature comparing with other phosphors as far as we know. The color coordinate values show that the NaGd1-x-ySiO4:×Dy3+-y Eu3+ phosphors are very close to the white light color coordinates (x=0.33, y=0.33) under 351 nm excitation. Meanwhile, the correlated color temperature is between 5062-7104 K. These results indicate that this phosphor is a promising candidate for high-quality WLED.

TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing cholesterol efflux capacity in macrophage.

Cholesterol efflux capacity (CEC) dysfunction in macrophages is important in atherosclerosis. However, the mechanism underlying CEC dysfunction remains unclear. We described the characteristics of ATF4 and inflammasome activation in macrophages during atherosclerosis through scRNA sequencing analysis. Then model of hyperlipemia was established in ApoE-/- mice; some were treated with tauroursodeoxycholic acid (TUDCA). TUDCA decreased the ATF4, Hspa, and inflammasome activation, reduced plaque area of the artery, and promoted CEC in macrophages. Furthermore, TUDCA abolished oxLDL-induced foam cell formation by inhibiting activation of the PERK/eIF2α/ATF4 and AIM2 inflammasome in macrophages. Further assays revealed ATF4 binding to AIM2 promoter, promoting its transcriptional activity significantly. Then we discovered that ATF4 affected AIM2-mediated foam cell formation by targeting ABCA1, which could be blocked by TUDCA. Our study demonstrated that TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing CEC of macrophage, which provided possibilities for the development of therapies.

Effect of fumigation height and time on cryopreservation of ram semen.

The cooling rate is a crucial factor in the process of freezing semen, influencing the overall freezing effectiveness. The height and time of fumigation can significantly impact the rate of cooling. Appropriate cooling rates can help minimize the formation of ice crystals in spermatozoa and reduce potential damage to them. Therefore, the aim of this study was to evaluate the effect of different fumigation heights and time for the cryopreservation of Hu ram semen. Experiments I-IV assessed the effect of semen cryopreservation by testing the post-thawed spermatozoa total motility (TM), progressive motility (PM) and kinetic parameters fumigated at distances of 2, 4, 6 and 8 cm for durations of 5, 10, 15 and 20 min, respectively. Based on the results of experiments I to IV, experiment V evaluated the effect of semen cryopreservation by testing the post-thawed spermatozoa TM, PM, kinetic parameters, plasma membrane integrity, acrosome integrity and reactive oxygen species (ROS) level fumigated at distances of 2, 4, 6 and 8 cm for duration of 20 min. The results indicated that fumigation at 2 cm for 20 min significantly (P < 0.05) improved spermatozoa TM, PM, mean angular displacement (MAD), plasma membrane integrity and acrosome integrity compared to other groups. Additionally, it significantly (P < 0.05) reduced spermatozoa ROS level compared to the 6 and 8 cm groups. In conclusion, fumigation for 20 min at a distance of 2 cm from the liquid nitrogen surface is the most suitable cooling method for the cryopreservation of Hu ram semen.

Analysis of nonlinear bending behavior of nano-switches considering surface effects.

Nano-switch structures are important control elements in nanoelectromechanical systems and have potential applications in future nanodevices. This paper analyzes the effects of surface effects, geometric nonlinearity, electrostatic forces, and intermolecular forces on the nonlinear bending behavior and adhesion stability of nano-switches. Based on the Von Karman geometric nonlinearity theory, four types of boundary conditions for the nano-switch structure were specifically calculated. The results show that surface effects have a significant impact on the nonlinear bending and adhesion stability of nano-switches. Surface effects increase the adhesion voltage of the nano-switch and decrease its adhesion displacement, and as the size of the nano-switch structure increases, the impact of surface effects decreases. A comparative analysis of the linear theory and the nonlinear theory results shows that the adhesion voltage predicted by the linear theory is smaller than that predicted by the nonlinear theory. The effect of geometric nonlinearity increases as the size of the nano-switch structure increases, as the distance between the electrodes increases, and as the aspect ratio of the nano-switch structure increases. These findings provide theoretical support and reference for the design and use of future nanodevices and nanoelectromechanical systems.

A survey of skin failure perceptions amongst pressure injury management staff in China: A cross-sectional study.

This study sought to evaluate the perceptions of pressure injury (PI) management staff regarding skin failure (SF). Additionally, an analysis of influencing factors based on the collected data was conducted to establish a foundation for targeted SF training. A descriptive, cross-sectional survey was undertaken in October-November 2023, utilising a convenience sampling method involving selected management staff of PI from 16 provinces in China. A total of 501 nursing participants were included, exhibiting an overall perception level that was moderately low. Although the majority were aware of the possibility of SF (n = 417, 83.23%), only 60% reported an understanding of the fundamentals of SF, with the lowest level of comprehension observed in differentiating between SF and PI (n = 212, 42.31%). Overall attitudes were generally positive. Regarding behaviour, active learning was more prevalent (n = 340, 67.86%), but training is less (n = 287, 57.29%). Family education (n = 401, 80.04%) and nursing record monitoring (n = 426, 85.03%) demonstrated better behaviour. Further analysis revealed that training (t = 13.937, p < 0.001) and professional title (F = 4.681, p = 0.010) had a significant effect on participants' perceptions. These findings underscore that there remains a substantial lack of perception about SF amongst participants. Overall, participants exhibited a positive attitude towards SF, highlighting the need for future improvements in SF training.

Biomarker-Driven DNA-Functionalized Colloidal Programmed Simultaneous Assembly and Disassembly in Cells.

Complex structures and devices, both natural and artificial, can often undergo assembly and disassembly. Assembly and disassembly allow multiple stimuli to initiate, for example, the assembly and disassembly of primary cilia under the control of E3 ubiquitin ligases and deubiquitinases. Although biology relies on such schemes, they are rarely available in materials science. Here, we demonstrate a DNA-functionalized colloidal Au response to endogenous biomarkers to trigger simultaneous assembly and disassembly techniques. Colloidal Au is initially inert because the starting DNA strands are paired and prehybridized. TK1 mRNA competes to bind one of the paired strands and release its complement. The released complement binds to the next colloidal Au to initiate assembly, and APE1 can shear the colloidal Au assembly binding site to initiate disassembly. Our strategy provides temporal and spatial logic control during colloidal Au assembly and disassembly, and this simultaneous assembly and disassembly process can be used for sequential detection and cellular imaging of two biomarkers, effectively reducing signal false-positive results and shortening detection time. This work highlights biomarker-controlled colloidal Au simultaneous assembly and disassembly in ways that are simple and versatile, with the potential to enrich the application scope of DNA nanotechnology and provide an idea for the application of precision medicine testing.

CRISPR/Cpf1-FOKI-induced gene editing in Gluconobacter oxydans.

Gluconobacter oxydans is an important Gram-negative industrial microorganism that produces vitamin C and other products due to its efficient membrane-bound dehydrogenase system. Its incomplete oxidation system has many crucial industrial applications. However, it also leads to slow growth and low biomass, requiring further metabolic modification for balancing the cell growth and incomplete oxidation process. As a non-model strain, G. oxydans lacks efficient genome editing tools and cannot perform rapid multi-gene editing and complex metabolic network regulation. In the last 15 years, our laboratory attempted to deploy multiple CRISPR/Cas systems in different G. oxydans strains and found none of them as functional. In this study, Cpf1-based or dCpf1-based CRISPRi was constructed to explore the targeted binding ability of Cpf1, while Cpf1-FokI was deployed to study its nuclease activity. A study on Cpf1 found that the CRISPR/Cpf1 system could locate the target genes in G. oxydans but lacked the nuclease cleavage activity. Therefore, the CRISPR/Cpf1-FokI system based on FokI nuclease was constructed. Single-gene knockout with efficiency up to 100% and double-gene iterative editing were achieved in G. oxydans. Using this system, AcrVA6, the anti-CRISPR protein of G. oxydans was discovered for the first time, and efficient genome editing was realized.