Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy.

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for "cell-free therapy" in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

Uncovering the characteristics of the gut microbiota in patients with ischemic stroke and hemorrhagic stroke.

This study aimed to explore the gut microbiota characteristics of ischemic and hemorrhagic stroke patients. A case-control study was conducted, and high-throughput sequencing of the V4-V5 region of 16S rRNA was used to analyze the differences in gut microbiota. The results showed that Proteobacteria was significantly increased in the ischemic stroke group compared with the healthy control group, while Fusobacteria was significantly increased in the hemorrhagic stroke group. In the ischemic stroke group, Butyricimonas, Alloprevotella, and Escherichia were significantly more abundant than in the healthy control group. In the hemorrhagic stroke group, Atopobium, Hungatella, Eisenbergiella, Butyricimonas, Odonbacter, Lachnociostridium, Alistipes, Parabacteroides, and Fusobacterium were significantly more abundant than in the healthy control group. Additionally, Alloprevotella, Ruminococcus, and Prevotella were significantly more abundant in the ischemic stroke group than in the hemorrhagic stroke group. The gut microbiota of ischemic and hemorrhagic stroke patients has significant diversity characteristics. These results provide new theoretical basis for exploring the prevention and treatment of different types of stroke through gut microbiota research.

High-performance terahertz modulators induced by substrate field in Te-based all-2D heterojunctions.

High-performance active terahertz modulators as the indispensable core components are of great importance for the next generation communication technology. However, they currently suffer from the tradeoff between modulation depth and speed. Here, we introduce two-dimensional (2D) tellurium (Te) nanofilms with the unique structure as a new class of optically controlled terahertz modulators and demonstrate their integrated heterojunctions can successfully improve the device performances to the optimal and applicable levels among the existing all-2D broadband modulators. Further photoresponse measurements confirm the significant impact of the stacking order. We first clarify the direction of the substrate-induced electric field through first-principles calculations and uncover the unusual interaction mechanism in the photoexcited carrier dynamics associated with the charge transfer and interlayer exciton recombination. This advances the fundamental and applicative research of Te nanomaterials in high-performance terahertz optoelectronics.

Synthesis, Characterization, and Catalytic Behaviors in Isoprene Polymerization of Pyridine-Oxazoline-Ligated Cobalt Complexes.

A family of pyridine-oxazoline-ligated cobalt complexes L2CoCl23a-h were synthesized and characterized. Determined via single-crystal X-ray diffraction, complexes 3a and 3d, ligated by two ligands, displayed a distorted tetrahedral coordination of a cobalt center. The X-ray structure indicated the pyridine-oxazoline ligands acted as unusual mono-dentate ligands by coordinating only to Noxazoline. Upon activation with AlEt2Cl (diethylaluminum chloride), these cobalt complexes all exhibited high catalytic activity (up to 2.5 × 106 g·molCo-1·h-1), affording cis-1,4-co-3,4-polyisoprene with molecular weights of 4.4-176 kg mol-1 and a narrow Ð of 1.79-3.42, suggesting a single-site nature of the active sites. The structure of cobalt catalysts and reaction parameters, especially co-catalysts and the reaction temperature, all have significant influence on the polymerization activity but not on the microstructure of polyisoprene.

KCNH6 is essential for insulin secretion by regulating intracellular ER Ca2+ store.

Appropriate Ca2+ concentration in the endoplasmic reticulum (ER), modulating cytosolic Ca2+ signal, serves significant roles in physiological function of pancreatic ß cells. To maintaining ER homeostasis, Ca2+ movement across the ER membrane is always accompanied by a simultaneous K+ flux in the opposite direction. KCNH6 was proven to modulate insulin secretion by controlling plasma membrane action potential duration and intracellular Ca2+ influx. Meanwhile, the specific function of KCNH6 in pancreatic ß-cells remains unclear. In this study, we found that KCNH6 exhibited mainly ER localization and Kcnh6 ß-cell-specific knockout (ßKO) mice suffered from abnormal glucose tolerance and impaired insulin secretion in adulthood. ER Ca2+ store was overloaded in islets of ßKO mice, which contributed to ER stress and ER stress-induced apoptosis in ß cells. Next, we verified that ethanol treatment induced increases in ER Ca2+ store and apoptosis in pancreatic ß cells, whereas adenovirus-mediated KCNH6 overexpression in islets attenuated ethanol-induced ER stress and apoptosis. In addition, tail-vein injections of KCNH6 lentivirus rescued KCNH6 expression in ßKO mice, restored ER Ca2+ overload and attenuated ER stress in ß cells, which further confirms that KCNH6 protects islets from ER stress and apoptosis. These data suggest that KCNH6 on the ER membrane may help to stabilize intracellular ER Ca2+ stores and protect ß cells from ER stress and apoptosis. In conclusion, our study reveals the protective potential of KCNH6-targeting drugs in ER stress-induced diabetes.

KCNH6 channel promotes insulin exocytosis via interaction with Munc18-1 independent of electrophysiological processes.

Glucose-stimulated insulin secretion (GSIS) in pancreatic islet ß-cells primarily relies on electrophysiological processes. Previous research highlighted the regulatory role of KCNH6, a member of the Kv channel family, in governing GSIS through its influence on ß-cell electrophysiology. In this study, we unveil a novel facet of KCNH6's function concerning insulin granule exocytosis, independent of its conventional electrical role. Young mice with ß-cell-specific KCNH6 knockout (ßKO) exhibited impaired glucose tolerance and reduced insulin secretion, a phenomenon not explained by electrophysiological processes alone. Consistently, islets from KCNH6-ßKO mice exhibited reduced insulin secretion, conversely, the overexpression of KCNH6 in murine pancreatic islets significantly enhanced insulin release. Moreover, insulin granules lacking KCNH6 demonstrated compromised docking capabilities and a reduced fusion response upon glucose stimulation. Crucially, our investigation unveiled a significant interaction between KCNH6 and the SNARE protein regulator, Munc18-1, a key mediator of insulin granule exocytosis. These findings underscore the critical role of KCNH6 in the regulation of insulin secretion through its interaction with Munc18-1, providing a promising and novel avenue for enhancing our understanding of the Kv channel in diabetes mechanisms.

Dynamical interplay between superconductivity and pseudogap in cuprates as revealed by terahertz third-harmonic generation spectroscopy.

We report on nonlinear terahertz third-harmonic generation (THG) measurements on YBa2Cu3O6+x thin films. Different from conventional superconductors, the THG signal starts to appear in the normal state, which is consistent with the crossover temperature T* of pseudogap over broad doping levels. Upon lowering the temperature, the THG signal shows an anomaly just below Tc in the optimally doped sample. Notably, we observe a beat pattern directly in the measured real-time waveform of the THG signal. We elaborate that the Higgs mode, which develops below Tc, couples to the mode already developed below T*, resulting in an energy level splitting. However, this coupling effect is not evident in underdoped samples. We explore different potential explanations for the observed phenomena. Our research offers valuable insight into the interplay between superconductivity and pseudogap.

Inference of Gene Regulatory Networks Based on Multi-view Hierarchical Hypergraphs.

Since gene regulation is a complex process in which multiple genes act simultaneously, accurately inferring gene regulatory networks (GRNs) is a long-standing challenge in systems biology. Although graph neural networks can formally describe intricate gene expression mechanisms, current GRN inference methods based on graph learning regard only transcription factor (TF)-target gene interactions as pairwise relationships, and cannot model the many-to-many high-order regulatory patterns that prevail among genes. Moreover, these methods often rely on limited prior regulatory knowledge, ignoring the structural information of GRNs in gene expression profiles. Therefore, we propose a multi-view hierarchical hypergraphs GRN (MHHGRN) inference model. Specifically, multiple heterogeneous biological information is integrated to construct multi-view hierarchical hypergraphs of TFs and target genes, using hypergraph convolution networks to model higher order complex regulatory relationships. Meanwhile, the coupled information diffusion mechanism and the cross-domain messaging mechanism facilitate the information sharing between genes to optimise gene embedding representations. Finally, a unique channel attention mechanism is used to adaptively learn feature representations from multiple views for GRN inference. Experimental results show that MHHGRN achieves better results than the baseline methods on the E. coli and S. cerevisiae benchmark datasets of the DREAM5 challenge, and it has excellent cross-species generalization, achieving comparable or better performance on scRNA-seq datasets from five mouse and two human cell lines.

All-potassium channel CRISPR screening reveals a lysine-specific pathway of insulin secretion.

OBJECTIVE: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of KATP depolarization and K+ repolarization. It is well known that glucose stimulates insulin secretion from pancreatic ß-cells, mainly via the KATP depolarization channel, but whether other nutrients directly regulate the repolarization K+ channel to promote insulin secretion is unknown. METHODS: We used a system involving CRISPR-Cas9-mediated knockout of all 83 K+ channels and scRNA-seq in a pancreatic ß cell line to identify genes associated with insulin secretion. RESULTS: The expression levels of insulin genes were significantly increased after all-K+ channel knockout. Furthermore, Kcnb1 and Kcnh6 were the two most important repolarization K+ channels for the increase in high-glucose-dependent insulin secretion that occurred upon application of specific inhibitors of the channels. Kcnh6 currents, but not Kcnb1 currents, were reduced by one of the amino acids, lysine, in both transfected cells, primary cells and mice with ß-cell-specific deletion of Kcnh6. CONCLUSIONS: Our function-related CRISPR screen with scRNA-seq identifies Kcnh6 as a lysine-specific channel.

Effectiveness and safety of probiotics on patients with severe acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the efficacy and safety of probiotics in conjunction with early enteral nutrition for the treatment of severe acute pancreatitis (SAP). This study focused on multiple clinical endpoints, including mortality rate, risk of organ failure, and duration of hospital stay. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study adhered to the Patient, Intervention, Comparison, Outcome framework and utilized randomized controlled trials to examine the impact of probiotics on patients with SAP. Data extraction and quality assessment were conducted independently by 2 evaluators, with discrepancies resolved collaboratively, or by a third adjudicator. Statistical analyses were performed using chi-square statistics, I2 metrics, and both fixed- and random-effects models, as dictated by heterogeneity levels. RESULTS: The meta-analysis covered 6 randomized controlled trials. Compared to control groups (placebo or standard care without probiotics), probiotics did not significantly reduce mortality rates or organ failure risk. However, they notably shortened hospital stays by a weighted mean difference of -5.49 days (95% confidence interval: -10.40 to -0.58; P = .010). The overall bias risk was low to moderate. CONCLUSIONS: Probiotics combined with early enteral nutrition did not significantly improve mortality rates or reduce the risk of organ failure in patients with SAP, but shortened hospital stays. Further studies are required to corroborate these findings.

Erratum: Upper limit of the transition temperature of superconducting materials.

[This corrects the article DOI: 10.1016/j.patter.2022.100609.].

Modeling the XBB strain of SARS-CoV-2: Competition between variants and impact of reinfection.

XBB, an Omicron subvariant of SARS-CoV-2 that began to circulate in late 2022, has been dominant in the US since early 2023. To quantify the impact of XBB on the progression of COVID-19, we propose a new mathematical model which describes the interplay between XBB and other SARS-CoV-2 variants at the population level and which incorporates the effects of reinfection. We apply the model to COVID-19 data in the US that include surveillance data on the cases and variant proportions from the New York City, the State of New York, and the State of Washington. Our fitting and simulation results show that the transmission rate of XBB is significantly higher than that of other variants and the reinfection from XBB may play an important role in shaping the pandemic/epidemic pattern in the US.

Xuebijing injection protects sepsis induced myocardial injury by mediating TLR4/NF-κB/IKKα and JAK2/STAT3 signaling pathways.

OBJECTIVE: Compelling evidence has demonstrated that Xuebijing (XBJ) exerted protective effects against SIMI. The aims of this study were to investigate whether TLR4/IKKα-mediated NF-κB and JAK2/STAT3 pathways were involved in XBJ's cardio-protection during sepsis and the mechanisms. METHODS: In this study, rats were randomly assigned to three groups: Sham group; CLP group; XBJ group. Rats were treated with XBJ or sanitary saline after CLP. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis were tested by TUNEL staining. The protein levels of Bax, Bcl-2, Bcl-xl, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3 in the myocardium were assayed by western blotting. And finally, immunofluorescence was used to assess the level of p-JAK2 and p-STAT3 in heart tissue. RESULTS: The results of echocardiography, myocardial enzyme and HE test showed that XBJ could significantly improve SIMI. The IL-1ß, IL-6 and TNF-α levels in the serum were markedly lower in the XBJ group than in the CLP group (p<0.05). TUNEL staining's results showed that XBJ ameliorated CLP-induced cardiomyocyte apoptosis. Meanwhile, XBJ downregulated the protein levels of Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cleaved-PARP, TLR4, p-NF-κB, p-IKKα, p-JAK2 and p-STAT3, as well as upregulated the protein levels of Bcl-2, Bcl-xl (p <0.05). CONCLUSIONS: In here, we observed that XBJ's cardioprotective advantages may be attributable to its ability to suppress inflammation and apoptosis via inhibiting the TLR4/ IKKα-mediated NF-κB and JAK2/STAT3 pathways during sepsis.

Black Phosphorus/Ferroelectric P(VDF-TrFE) Field-Effect Transistors with High Mobility for Energy-Efficient Artificial Synapse in High-Accuracy Neuromorphic Computing.

The neuromorphic system is an attractive platform for next-generation computing with low power and fast speed to emulate knowledge-based learning. Here, we design ferroelectric-tuned synaptic transistors by integrating 2D black phosphorus (BP) with a flexible ferroelectric copolymer poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)). Through nonvolatile ferroelectric polarization, the P(VDF-TrFE)/BP synaptic transistors show a high mobility value of 900 cm2 V-1 s-1 with a 103 on/off current ratio and can operate with low energy consumption down to the femtojoule level (∼40 fJ). Reliable and programmable synaptic behaviors have been demonstrated, including paired-pulse facilitation, long-term depression, and potentiation. The biological memory consolidation process is emulated through ferroelectric gate-sensitive neuromorphic behaviors. Inspiringly, the artificial neural network is simulated for handwritten digit recognition, achieving a high recognition accuracy of 93.6%. These findings highlight the prospects of 2D ferroelectric field-effect transistors as ideal building blocks for high-performance neuromorphic networks.

Photoinduced Phase Transition in Infinite-Layer Nickelates.

The quantum phase transition caused by regulating the electronic correlation in strongly correlated quantum materials has been a research hotspot in condensed matter science. Herein, a photon-induced quantum phase transition from the Kondo-Mott insulating state to the low temperature metallic one accompanying with the magnetoresistance changing from negative to positive in the infinite-layer NdNiO2 films is reported, where the antiferromagnetic coupling among the Ni1+ localized spins and the Kondo effect are effectively suppressed by manipulating the correlation of Ni-3d and Nd-5d electrons under the photoirradiation. Moreover, the critical temperature Tc of the superconducting-like transition exhibits a dome-shaped evolution with the maximum up to ≈42 K, and the electrons dominate the transport process proved by the Hall effect measurements. These findings not only make the photoinduction a promising way to control the quantum phase transition by manipulating the electronic correlation in Mott-like insulators, but also shed some light on the possibility of the superconducting in electron-doped nickelates.

Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus.

Continuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid-base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts' clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts' consensus.

TC-Net: A joint learning framework based on CNN and vision transformer for multi-lesion medical images segmentation.

BACKGROUND: With the rapid advancement of medical imaging technology, the demand for accurate segmentation of medical images is increasing. However, most existing methods are unable to capture locality and long-range dependency information in integrated ways for medical images. METHOD: In this paper, we propose an elegant segmentation framework for medical images named TC-Net, which can utilize both the locality-aware and long-range dependencies in the medical images. As for the locality-aware perspective, we employ a CNN-based encoder and decoder structure. The CNN branch uses the locality of convolution operations to dig out local information in medical images. As for the long-range dependencies, we construct a Transformer branch to focus on the global context. Additionally, we proposed a locality-aware and long-range dependency concatenation strategy (LLCS) to aggregate the feature maps obtained from the two subbranches. Finally, we present a dynamic cyclical focal loss (DCFL) to address the class imbalance problem in multi-lesion segmentation. RESULTS: Comprehensive experiments were conducted on lesion segmentation tasks using two fundus image databases and a skin image database. The TC-Net achieves scores of 0.6985 and 0.5171 in the metric of mean pixel accuracy on the IDRiD and DDR databases, respectively. Moreover, on the skin image database, the TC-Net reached mean pixel accuracy of 0.8886. The experiment results demonstrate that the proposed method achieves better performance than other deep learning segmentation schemes. Furthermore, the proposed DCFL achieves higher performance than other loss functions in multi-lesion segmentation. SIGNIFICANCE: The proposed TC-Net is a promising new framework for multi-lesion medical image segmentation and many other challenging image segmentation tasks. © 2001 Elsevier Science. All rights reserved.

Association between Covid-19 vaccination and incidence of type 1 diabetes in China: Evidence from 14.14 million registered residents between 2007 and 2021.

AIMS: Reports have suggested that COVID-19 vaccination may cause Type 1 diabetes (T1D), particularly fulminant T1D (FT1D). This study aimed to investigate the incidence of T1D in a general population of China, where>90% of the people have received three injections of inactivated SARS-Cov-2 vaccines in 2021. METHODS: A population-based registry of T1D was performed using data from the Beijing Municipal Health Commission Information Center. Annual incidence rates were calculated by age group and gender, and annual percentage changes were assessed using Joinpoint regression. RESULTS: The study included 14.14 million registered residents, and 7,697 people with newly diagnosed T1D were identified from 2007 to 2021. T1D incidence increased from 2.77 in 2007 to 3.84 per 100,000 persons in 2021. However, T1D incidence was stable from 2019 to 2021, and the incidence rate did not increase when people were vaccinated in January-December 2021. The incidence of FT1D did not increase from 2015 to 2021. CONCLUSIONS: The findings suggest that COVID-19 vaccination did not increase the onset of T1D or have a significant impact on T1D pathogenesis, at least not on a large scale.

Germacrane Sesquiterpene Dilactones from Mikania micrantha and Their Antibacterial and Cytotoxic Activity.

Four new germacrane sesquiterpene dilactones, 2ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (1), 3ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (2), 1α,3ß-dihydroxy-4,9-germacradiene-12,8:15,6-diolide (3), and (11ß,13-dihydrodeoxymikanolide-13-yl)-adenine (4), together with five known ones (5-9) were isolated from the aerial parts of Mikania micrantha. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 4 is featured with an adenine moiety in the molecule, which is the first nitrogen-containing sesquiterpenoid so far isolated from this plant species. These compounds were evaluated for their in vitro antibacterial activity against four Gram-(+) bacteria of Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC) and Curtobacterium. flaccumfaciens (CF), and three Gram-(-) bacteria of Escherichia coli (EC), Salmonella. typhimurium (SA), and Pseudomonas Solanacearum (PS). Compounds 4 and 7-9 were found to show strong in vitro antibacterial activity toward all the tested bacteria with the MIC values ranging from 1.56 to 12.5 µg/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 µg/mL, which was close to reference compound vancomycin (MIC 3.125 µg/mL). Compounds 4 and 7-9 were further revealed to show in vitro cytotoxic activity toward human tumor A549, HepG2, MCF-7, and HeLa cell lines, with IC50 values ranging from 8.97 to 27.39 µM. No antibacterial and cytotoxic activity were displayed for the other compounds. The present research provided new data to support that M. micrantha is rich in structurally diverse bioactive compounds worthy of further development for pharmaceutical applications and for crop protection in agricultural fields.