Regeneration Roadmap: database resources for regenerative biology.

Regeneration plays an instrumental role in biological development and damage repair by constructing and replacing cells, tissues, and organs. Since regenerative capacity declines with age, promoting regeneration is heralded as a potential strategy for delaying aging. On this premise, mechanisms that regulate regeneration have been extensively studied across species and in different tissues. However, an open and comprehensive database collecting and standardizing the abundant data generated in regeneration research, such as high-throughput sequencing data, remains to be developed. In this work, we constructed Regeneration Roadmap to systematically and comprehensively collect such information over 2.38 million data entries across 11 species and 36 tissues, including regeneration-related genes, bulk and single-cell transcriptomics, epigenomics, and pharmacogenomics data. In this database, users can explore regulatory and expression changes of regeneration-associated genes in different species and tissues. Regeneration Roadmap provides the research community with a long-awaited and valuable data resource featuring convenient computing and visualizing tools, which is publicly available at https://ngdc.cncb.ac.cn/regeneration/index.

Spring irrigation with magnetized water affects soil water-salt distribution, emergence, growth, and photosynthetic characteristics of cotton seedlings in Southern Xinjiang, China.

BACKGROUND: Spring irrigation with freshwater is widely used to reduce soil salinity and increase the soil water content in arid areas. However, this approach requires a huge amount of freshwater, which is problematic given limited freshwater resources. Utilizing brackish water for spring irrigation in combination with magnetized water technology may be a promising alternative strategy. RESULTS: The objective of this study was to evaluate the effects of four spring irrigation methods (freshwater spring irrigation (FS), magnetized freshwater spring irrigation (MFS), brackish water spring irrigation (BS), and magnetized brackish water spring irrigation (MBS)) on soil water and salt distribution, emergence, growth, and photosynthetic characteristics of cotton seedlings. The results showed that for both freshwater and brackish water, magnetized water irrigation can increase the soil water content for improved desalination effect of irrigation water. Additionally, spring irrigation with magnetized water promoted cotton emergence and seedling growth. Compared with FS treatment, cotton finial emergence rate, emergence index, vigor index, plant height, stem diameter, and leaf area index of MFS treatment increased by 6.25, 7.19, 12.98, 15.60, 8.91, and 20.57%, respectively. Compared with BS treatment, cotton finial emergence rate, emergence index, vigor index, plant height, stem diameter, and leaf area index of MBS treatment increased by 27.78, 39.83, 74.79, 26.40, 14.01, and 57.22%, respectively. Interestingly, we found that spring irrigation with magnetized water can increase the chlorophyll content and net photosynthetic rate of cotton seedlings. The rectangular hyperbolic model (RHM), non-rectangular hyperbolic model (NRHM), exponential model (EM), and modified rectangular hyperbolic model (MRHM) were used to fit and compare the cotton light response curve, and MRHM was determined to be the optimal model to fit the data. This model was used to calculate the photosynthetic parameters of cotton. Compared with FS treatment, the net photosynthetic rate (Pnmax), dark respiration rate (Rd), light compensation point (Ic), light saturation point (Isat), and the range of available light intensity (ΔI) of MFS were increased by 5.18, 3.41, 3.18, 2.29 and 2.19%, respectively. Compared with BS treatment, the Pnmax, Rd, Ic, Isat and ΔI of MBS were increased by 26.44, 29.48, 30.05, 5.13, and 2.27%, respectively. CONCLUSION: The results show that spring irrigation with magnetized brackish water may be a feasible method to reduce soil salt and increase soil water content when freshwater resources are insufficient.

Molecular dynamics simulation on the Thermosinus carboxydivorans pfl ZTP riboswitch by ligand binding.

Riboswitches are RNA molecules that can regulate gene expression which is affected by ligand-binding during cotranscriptional folding process. However, the role of ligand during the folding is still unclear. In this study, the pfl domain of Thermosinus carboxydivorans ZTP riboswitch was discussed. The ligand is molecule ZMP. We mainly analyzed the change of ZMP-free and ZMP-bound aptamer domain by the dynamics simulation method. Structural features by calculating their RMSD, RMSF, etc. are analyzed. The results demonstrate that the binding domain require the presence of ZMP to maintain a stable fold. It also suggested that ZMP specificly binding to ZTP can generate more hydrogen bonds in the binding domain. Through the calculation of binding free energy decomposition of each nucleotide, molecule ZMP was found to promote the recognition and binding process of ligands by controlling some special nucleotides in the process of ligand binding. At last, the dynamical correlation and components of conformational motions were both applied to explore the effect of molecule ZMP to ZTP riboswitch. In general, ZMP can effectively affect the motions of the pfl riboswitch and facilitate the folding process of the ZTP riboswitch.These results may provide some new ideas for structural changes in riboswitches and their cotranscriptional folding process.

Surface acoustic wave controlled skyrmion-based synapse devices.

Magnetic skyrmions, which are particle-like spin structures, are promising information carriers for neuromorphic computing devices due to their topological stability and nanoscale size. In this work, we propose controlling magnetic skyrmions by electric-field-excited surface acoustic waves in neuromorphic computing device structures. Our micromagnetic simulations show that the number of created skyrmions, which emulates the synaptic weight parameter, increases monotonically with increases in the amplitude of the surface acoustic waves. Additionally, the efficiency of skyrmion creation is investigated systemically with a wide range of magnetic parameters, and the optimal values are presented accordingly. Finally, the functionalities of short-term plasticity and long-term potentiation are demonstrated via skyrmion excitation by a sequence of surface acoustic waves with different intervals. The application of surface acoustic waves in skyrmionic neuromorphic computing devices paves a novel approach to low-power computing systems.

Magnetic skyrmion-based synaptic devices.

Magnetic skyrmions are promising candidates for next-generation information carriers, owing to their small size, topological stability, and ultralow depinning current density. A wide variety of skyrmionic device concepts and prototypes have recently been proposed, highlighting their potential applications. Furthermore, the intrinsic properties of skyrmions enable new functionalities that may be inaccessible to conventional electronic devices. Here, we report on a skyrmion-based artificial synapse device for neuromorphic systems. The synaptic weight of the proposed device can be strengthened/weakened by positive/negative stimuli, mimicking the potentiation/depression process of a biological synapse. Both short-term plasticity and long-term potentiation functionalities have been demonstrated with micromagnetic simulations. This proposal suggests new possibilities for synaptic devices in neuromorphic systems with adaptive learning function.

Magnetic skyrmion-based artificial neuron device.

Neuromorphic computing, inspired by the biological nervous system, has attracted considerable attention. Intensive research has been conducted in this field for developing artificial synapses and neurons, attempting to mimic the behaviors of biological synapses and neurons, which are two basic elements of a human brain. Recently, magnetic skyrmions have been investigated as promising candidates in neuromorphic computing design owing to their topologically protected particle-like behaviors, nanoscale size and low driving current density. In one of our previous studies, a skyrmion-based artificial synapse was proposed, with which both short-term plasticity and long-term potentiation functions have been demonstrated. In this work, we further report on a skyrmion-based artificial neuron by exploiting the tunable current-driven skyrmion motion dynamics, mimicking the leaky-integrate-fire function of a biological neuron. With a simple single-device implementation, this proposed artificial neuron may enable us to build a dense and energy-efficient spiking neuromorphic computing system.

Prognostic value of mixed lineage kinase domain-like protein expression in the survival of patients with gastric caner.

The aim of this study was to detect mixed lineage kinase domain-like protein (MLKL) expression in gastric cancer (GC) and to analyze its association with the prognosis of GC patients. Immunohistochemical staining, Western blotting, and quantitative reverse-transcriptase polymerase chain reaction were performed to detect MLKL tissue expression in 117 GC patients. Clinicopathological characteristics and survival data were retrospectively analyzed to discover the clinical importance of MLKL expression. The chi-square test was used to analyze the relationship between MLKL expression and the clinicopathological characteristics. Survival curves were plotted by using the Kaplan-Meier method and compared using the log-rank test. Survival data were evaluated using univariate and multivariate Cox regression analyses. The expression of MLKL mRNA was significantly higher in adjacent normal samples than in the tumor tissues (P = 0.003). Clinicopathological analysis showed that MLKL expression was significantly correlated with age (P = 0.013), histologic type (P = 0.049), differentiation grade (P < 0.001), depth of invasion (P = 0.022), and lymph node metastasis (P = 0.003). Low MLKL expression was significantly associated with decreased overall survival (median 29 months vs. 56 months, P < 0.001). Multivariate analysis suggested that MLKL expression might be an independent prognostic indicator (HR = 0.645, 95 % CI, 0.446-1.165, P = 0.002) for GC patients. In conclusion, our findings provide evidence that MLKL might serve as a candidate tumor suppressor and a potential prognostic biomarker for GC.

EGFR mediates docetaxel resistance in human castration-resistant prostate cancer through the Akt-dependent expression of ABCB1 (MDR1).

Recent studies have shown that docetaxel-based chemotherapy confers a survival benefit in patients with castration-resistant prostate cancer (PC). Also epidermal growth factor receptor (EGFR) was found to have multiple roles in prostatic tumorigenesis. However, the EGFR-mediated chemoresistance mechanism in human PC was not well delineated. In this study, we explored the mechanism of EGFR-mediated docetaxel resistance in PC. A series of stable docetaxel-resistant PC/DX sublines were established at our laboratory. The docetaxel IC50s of PC3 and PC/DX25 cells were 0.01 and 1.33 µM, respectively. Cellular resistance to docetaxel was significantly associated with increased EGFR and EGFR activation in PC/DX25. There was a dose-dependent increase in EGFR expression associated with the magnitude of docetaxel resistance. Expression of EGFR in PC/DX25 was higher than that in PC3, RWPE-1 and LNCaP cells. Similar results were also found in human PC tissues by immunohistochemical staining. We showed that docetaxel sensitivity can be stored in PC/DX25 cells by knockdown and inactivation of EGFR expression through EGFR siRNA and specific inhibitors, respectively. Contrarily, overexpression of EGFR or recombinant EGF protein treatment could rescue PC3 cells from docetaxel-mediated cytotoxicity. Gefitninb (ZD1839) significantly inhibited the growth of PC/DX25 cells by MTT in vitro and on xenografted nude mice in vivo. Moreover, EGFR-mediated docetaxel resistance occurred through the Akt-dependent ABCB1 expression in PC cells. These findings demonstrated EGFR played an important role in docetaxel-resistant PC and EGFR inhibition may enhance the therapeutic efficacy of docetaxel-based treatment.

Patient satisfaction analysis of robot-assisted minimally invasive adrenalectomy: a single-center retrospective study.

The objective of this study is to compare the satisfaction of patients undergoing robot-assisted retroperitoneal laparoscopy adrenalectomy under the ambulatory mode and conventional mode. Basic information and clinical data of patients who underwent robotic-assisted posterior laparoscopic adrenalectomy between June 2020 and June 2023 were queried from our case system. The Outpatient and Ambulatory Surgery Consumer Assessment of Healthcare Providers and Systems Survey (OAS CAHPS®) was used to investigate patient satisfaction with preoperative preparation, discharge counseling, postoperative instructions, postoperative pain, and satisfaction with nursing work. The stats R package was used to select the appropriate statistic for the statistics based on the characteristics of the data. A total of 311 patients who underwent robot-assisted posterior laparoscopic adrenalectomy were enrolled in our case system. There were no statistical differences between the two groups in gender, age, body mass index, ASA classification, laterality, maximum tumor diameter, type of resection, hormonal activity, disease type, pathological classification, duration of surgery, estimated intraoperative bleeding, postoperative complications and follow-up period that were compared between the two groups of patients. There were no significant differences in preoperative preparation score, discharge counseling score, postoperative guidance score and nursing care satisfaction score (P > 0.05). Postoperative hospitalization, peristalsis time, defecation time, time to first postoperative mobilization, duration of indwelling drain and hospitalization costs in patients in the ambulatory model group were significantly less than patients in the conventional model group (P < 0.001). Patients in the ambulatory model group had significantly higher postoperative pain relief scores than patients in the conventional model group. In conclusion, our data suggest that patient satisfaction is equal between the conventional and ambulatory mode of performing robotic-assisted adrenalectomy. Patient satisfaction was probably associated with shorter hospitalization days, adequate preoperative preparation and standardized, high-quality post-discharge information and guidance.

A Rare Cause of Chronic Flexor Tenosynovitis of the Finger.

Cat scratch disease (CSD) is an uncommon condition. When a patient is infected, the disease is often self-limiting. Cat scratch disease involving the musculoskeletal system had been described, but the manifestation of the disease in hand remained unexplored. We report a case of chronic flexor tenosynovitis of the left index finger caused by cat scratch disease. In this case, the antibiotic treatment did not improve the clinical outcome. However, surgical debridement of the diseased finger resulted in a tremendous improvement in terms of pain and range of motion.

Experimental demonstration of a skyrmion-enhanced strain-mediated physical reservoir computing system.

Physical reservoirs holding intrinsic nonlinearity, high dimensionality, and memory effects have attracted considerable interest regarding solving complex tasks efficiently. Particularly, spintronic and strain-mediated electronic physical reservoirs are appealing due to their high speed, multi-parameter fusion and low power consumption. Here, we experimentally realize a skyrmion-enhanced strain-mediated physical reservoir in a multiferroic heterostructure of Pt/Co/Gd multilayers on (001)-oriented 0.7PbMg1/3Nb2/3O3-0.3PbTiO3 (PMN-PT). The enhancement is coming from the fusion of magnetic skyrmions and electro resistivity tuned by strain simultaneously. The functionality of the strain-mediated RC system is successfully achieved via a sequential waveform classification task with the recognition rate of 99.3% for the last waveform, and a Mackey-Glass time series prediction task with normalized root mean square error (NRMSE) of 0.2 for a 20-step prediction. Our work lays the foundations for low-power neuromorphic computing systems with magneto-electro-ferroelastic tunability, representing a further step towards developing future strain-mediated spintronic applications.

Down-regulation of PKCζ in renal cell carcinoma and its clinicopathological implications.

BACKGROUND: Metastatic renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy. Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC. Recent studies have shown the atypical PKCζ is an important regulator of tumorigenesis. However, the correlation between PKCζ expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCζ expression in human RCC. METHODS: PKCζ mRNA and protein expressions were examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular cytotoxicity and proliferation were assessed by MTT. RESULTS: PKCζ expression was significantly higher in normal than in cancerous tissues (P<0.0001) by real-time PCR and IHC. Similarly, PKCζ expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (P=0.04), but no such association was found in TNM stage (P=0.13). Tumors with higher PKCζ expression were associated with tumor size (P=0.048). Expression of higher PKCζ found a poor survival in patients with high tumor grade. Down-regulation of PKCζ showed the significant chemoresistance in RCC cell lines. Inactivation of PKCζ expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKCζ siRNA and inhibitor. CONCLUSIONS: PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.

Forecasting the outcome of spintronic experiments with Neural Ordinary Differential Equations.

Deep learning has an increasing impact to assist research, allowing, for example, the discovery of novel materials. Until now, however, these artificial intelligence techniques have fallen short of discovering the full differential equation of an experimental physical system. Here we show that a dynamical neural network, trained on a minimal amount of data, can predict the behavior of spintronic devices with high accuracy and an extremely efficient simulation time, compared to the micromagnetic simulations that are usually employed to model them. For this purpose, we re-frame the formalism of Neural Ordinary Differential Equations to the constraints of spintronics: few measured outputs, multiple inputs and internal parameters. We demonstrate with Neural Ordinary Differential Equations an acceleration factor over 200 compared to micromagnetic simulations for a complex problem - the simulation of a reservoir computer made of magnetic skyrmions (20 minutes compared to three days). In a second realization, we show that we can predict the noisy response of experimental spintronic nano-oscillators to varying inputs after training Neural Ordinary Differential Equations on five milliseconds of their measured response to a different set of inputs. Neural Ordinary Differential Equations can therefore constitute a disruptive tool for developing spintronic applications in complement to micromagnetic simulations, which are time-consuming and cannot fit experiments when noise or imperfections are present. Our approach can also be generalized to other electronic devices involving dynamics.

CRISPR FISHer enables high-sensitivity imaging of nonrepetitive DNA in living cells through phase separation-mediated signal amplification.

The dynamic three-dimensional structures of chromatin and extrachromosomal DNA molecules regulate fundamental cellular processes and beyond. However, the visualization of specific DNA sequences in live cells, especially nonrepetitive sequences accounting for most of the genome, is still vastly challenging. Here, we introduce a robust CRISPR-mediated fluorescence in situ hybridization amplifier (CRISPR FISHer) system, which exploits engineered sgRNA and protein trimerization domain-mediated, phase separation-based exponential assembly of fluorescent proteins in the CRISPR-targeting locus, conferring enhancements in both local brightness and signal-to-background ratio and thus achieving single sgRNA-directed visualization of native nonrepetitive DNA loci in live cells. In one application, by labeling and tracking the broken ends of chromosomal fragments, CRISPR FISHer enables real-time visualization of the entire process of chromosome breakage, separation, and subsequent intra- or inter-chromosomal ends rejoining in a single live cell. Furthermore, CRISPR FISHer allows the movement of small extrachromosomal circular DNAs (eccDNAs) and invading DNAs to be recorded, revealing substantial differences in dynamic behaviors between chromosomal and extrachromosomal loci. With the potential to track any specified self or non-self DNA sequences, CRISPR FISHer dramatically broadens the scope of live-cell imaging in biological events and for biomedical diagnoses.

Experimental demonstration of skyrmionic magnetic tunnel junction at room temperature.

Chiral magnetic skyrmions are topological swirling spin textures that hold promise for future information technology. The electrical nucleation and motion of skyrmions have been experimentally demonstrated in the last decade, while electrical detection compatible with semiconductor processes has not been achieved, and this is considered one of the most crucial gaps regarding the use of skyrmions in real applications. Here, we report the direct observation of nanoscale skyrmions in CoFeB/MgO-based magnetic tunnel junction devices at room temperature. High-resolution magnetic force microscopy imaging and tunneling magnetoresistance measurements are used to illustrate the electrical detection of skyrmions, which are stabilized under the cooperation of interfacial Dzyaloshinskii-Moriya interaction, perpendicular magnetic anisotropy, and dipolar stray field. This skyrmionic magnetic tunnel junction shows a stable nonlinear multilevel resistance thanks to its topological nature and tunable density of skyrmions under current pulse excitation. These features provide important perspectives for spintronics to realize high-density memory and neuromorphic computing.

Magnetic skyrmions for unconventional computing.

Improvements in computing performance have significantly slowed down over the past few years owing to the intrinsic limitations of computing hardware. However, the demand for data computing has increased exponentially. To solve this problem, tremendous attention has been focused on the continuous scaling of Moore's law as well as the advanced non-von Neumann computing architecture. A rich variety of unconventional computing paradigms has been devised with the rapid development of nanoscale devices. Magnetic skyrmions, spin swirling quasiparticles, have been endowed with great expectations for unconventional computing due to their potential as the smallest information carriers by exploiting their physics and dynamics. In this paper, we provide an overview of the recent progress of skyrmion-based unconventional computing from a joint device-application perspective. This paper aims to build up a panoramic picture, analyze the remaining challenges, and most importantly to shed light on the outlook of skyrmion based unconventional computing for interdisciplinary researchers.

Above Room-Temperature Ferromagnetism in Wafer-Scale Two-Dimensional van der Waals Fe3GeTe2 Tailored by a Topological Insulator.

The emerging two-dimensional ferromagnetic materials present atomic layer thickness and a perfect interface feature, which have become an attractive research direction in the field of spintronics for low power and deep nanoscale integration. However, it has been proven to be extremely challenging to achieve a room-temperature ferromagnetic candidate with well controlled dimensionality, large-scale production, and convenient heterogeneous integration. Here, we report the growth of wafer-scale two-dimensional Fe3GeTe2 integrated with a topological insulator of Bi2Te3 by molecular beam epitaxy, which shows a Curie temperature (Tc) up to 400 K with perpendicular magnetic anisotropy. Dimensionality-dependent magnetic and magnetotransport measurements find that Tc increases with decreasing Fe3GeTe2 thickness in the heterostructures, indicating an interfacial engineering effect from Bi2Te3. The theoretical calculation further proves that the interfacial exchange coupling could significantly enhance the intralayer spin interaction in Fe3GeTe2, hence giving rise to a higher Tc. Our results provide great potential for the implementation of high-performance spintronic devices based on two-dimensional ferromagnetic materials.

Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma.

Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and hormonal therapies. Previous studies have shown over-expression of EGFR is associated with high grade tumors and a worse prognosis. Recent studies suggest anticancer therapies targeting the EGFR pathway have shown promising results in clinical trials of RCC patients. Therefore, characterization of the level and localization of EGFR expression in RCC is important for target-dependent therapy. In this study, we investigated the clinical significance of cellular localization of EGFR in human normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63 patients were obtained for characterization of EGFR expression. EGFR protein expression was assessed by immunohistochemistry on a scale from 0 to 300 (percentage of positive cells x staining intensity) and Western blotting. EGFR membranous staining was significantly stronger in RCC tumors than in normal tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly higher in normal than in tumor tissues (P < 0.001). The levels of membranous or cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor grade, TNM stage or overall survival (P > 0.05). These results showed abundant expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR in normal tissues. EGFR expression in RCC was mostly located in the cell membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in cytoplasm. Our results suggest different locations of EGFR expression may be associated with human renal tumorigenesis.

Downregulation of ABCD1 in human renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. Delayed diagnosis may result in progression and metastasis. Markers for early detection of RCC are lacking. The ATP-binding cassette transporter D1 (ABCD1) is located in the human peroxisome membrane. Its mutation causes X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disorder affecting lipid storage. The role of ABCD1 in human renal tumorigenesis was unclear. In this study, three pairs of RCC tissues were examined by cDNA microarray and data suggested that ABCD1 mRNA is downregulated. Downregulation of ABCD1 expression was confirmed by real-time PCR. ABCD1 expression was also downregulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. ABCD1 mRNA and protein expression levels assessed by immunohistochemistry in the RCC tissues were similar between genders, tumor grades, and tumor stages. Immunohistochemical assays also showed that ABCD1 expression was significantly higher in normal than in cancerous tissues (p<0.001). ABCD1 downregulation may be involved in human renal tumorigenesis.