A rabbit osteochondral defect (OCD) model for evaluation of tissue engineered implants on their biosafety and efficacy in osteochondral repair.

Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant's biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.

Neural mechanism of non-adaptive cognitive emotion regulation in patients with non-suicidal self-injury.

BACKGROUND: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. METHODS: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. RESULTS: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = -4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log108) and "modulation of chemical synaptic transmission" (p < -log108) in both cells. CONCLUSIONS: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623.

Low-loss and compact, dual-mode, 3-dB power splitter combining a directional coupler, a multimode interferometer, and a Y-junction.

Multimode power splitters are the fundamental building blocks in mode division multiplexing systems. In this paper, we propose a low-loss and compact, dual-mode, 3-dB power splitter for the two lowest TE modes combining three different structures, including a directional coupler, a multimode interferometer, and a Y-junction. The coupling length of the proposed device is only 7.2 µm. For both T E 0 and T E 1 modes, the numerical simulation shows that the insertion loss is only less than 0.1 dB and crosstalk is less than -20d B at the wavelength range of 1520-1580 nm. The working bandwidth can cover the entire C-band. It offers a potential solution for a 3-dB power splitter of the two lowest TE modes.

Investigating human-derived lactic acid bacteria for alcohol resistance.

BACKGROUND: Excessive alcohol consumption has been consistently linked to serious adverse health effects, particularly affecting the liver. One natural defense against the detrimental impacts of alcohol is provided by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), which detoxify harmful alcohol metabolites. Recent studies have shown that certain probiotic strains, notably Lactobacillus spp., possess alcohol resistance and can produce these critical enzymes. Incorporating these probiotics into alcoholic beverages represents a pioneering approach that can potentially mitigate the negative health effects of alcohol while meeting evolving consumer preferences for functional and health-centric products. RESULTS: Five lactic acid bacteria (LAB) isolates were identified: Lactobacillus paracasei Alc1, Lacticaseibacillus rhamnosus AA, Pediococcus acidilactici Alc3, Lactobacillus paracasei Alc4, and Pediococcus acidilactici Alc5. Assessment of their alcohol tolerance, safety, adhesion ability, and immunomodulatory effects identified L. rhamnosus AA as the most promising alcohol-tolerant probiotic strain. This strain also showed high production of ADH and ALDH. Whole genome sequencing analysis revealed that the L. rhamnosus AA genome contained both the adh (encoding for ADH) and the adhE (encoding for ALDH) genes. CONCLUSIONS: L. rhamnosus AA, a novel probiotic candidate, showed notable alcohol resistance and the capability to produce enzymes essential for alcohol metabolism. This strain is a highly promising candidate for integration into commercial alcoholic beverages upon completion of comprehensive safety and functionality evaluations.

Impaired topology and connectivity of grey matter structural networks in major depressive disorder: evidence from a multi-site neuroimaging data-set.

BACKGROUND: Major depressive disorder (MDD) has been increasingly understood as a disruption of brain connectome. Investigating grey matter structural networks with a large sample size can provide valuable insights into the structural basis of network-level neuropathological underpinnings of MDD. AIMS: Using a multisite MRI data-set including nearly 2000 individuals, this study aimed to identify robust topology and connectivity abnormalities of grey matter structural network linked to MDD and relevant clinical phenotypes. METHOD: A total of 955 MDD patients and 1009 healthy controls were included from 23 sites. Individualised structural covariance networks (SCN) were established based on grey matter volume maps. Following data harmonisation, network topological metrics and focal connectivity were examined for group-level comparisons, individual-level classification performance and association with clinical ratings. Various validation strategies were applied to confirm the reliability of findings. RESULTS: Compared with healthy controls, MDD individuals exhibited increased global efficiency, abnormal regional centralities (i.e. thalamus, precentral gyrus, middle cingulate cortex and default mode network) and altered circuit connectivity (i.e. ventral attention network and frontoparietal network). First-episode drug-naive and recurrent patients exhibited different patterns of deficits in network topology and connectivity. In addition, the individual-level classification of topological metrics outperforms that of structural connectivity. The thalamus-insula connectivity was positively associated with the severity of depressive symptoms. CONCLUSIONS: Based on this high-powered data-set, we identified reliable patterns of impaired topology and connectivity of individualised SCN in MDD and relevant subtypes, which adds to the current understanding of neuropathology of MDD and might guide future development of diagnostic and therapeutic markers.

Comparative plastome analysis of the sister genera Ceratocephala and Myosurus (Ranunculaceae) reveals signals of adaptive evolution to arid and aquatic environments.

BACKGROUND: Expansion and contraction of inverted repeats can cause considerable variation of plastid genomes (plastomes) in angiosperms. However, little is known about whether structural variations of plastomes are associated with adaptation to or occupancy of new environments. Moreover, adaptive evolution of angiosperm plastid genes remains poorly understood. Here, we sequenced the complete plastomes for four species of xerophytic Ceratocephala and hydrophytic Myosurus, as well as Ficaria verna. By an integration of phylogenomic, comparative genomic, and selection pressure analyses, we investigated evolutionary patterns of plastomes in Ranunculeae and their relationships with adaptation to dry and aquatic habitats. RESULTS: Owing to the significant contraction of the boundary of IRA/LSC towards the IRA, plastome sizes and IR lengths of Myosurus and Ceratocephala are smaller within Ranunculeae. Compared to other Ranunculeae, the Myosurus plastome lost clpP and rps16, one copy of rpl2 and rpl23, and one intron of rpoC1 and rpl16, and the Ceratocephala plastome added an infA gene and lost one copy of rpl2 and two introns of clpP. A total of 11 plastid genes (14%) showed positive selection, two genes common to Myosurus and Ceratocephala, seven in Ceratocephala only, and two in Myosurus only. Four genes showed strong signals of episodic positive selection. The rps7 gene of Ceratocephala and the rpl32 and ycf4 genes of Myosurus showed an increase in the rate of variation close to 3.3 Ma. CONCLUSIONS: The plastomic structure variations as well as the positive selection of two plastid genes might be related to the colonization of new environments by the common ancestor of Ceratocephala and Myosurus. The seven and two genes under positive selection might be related to the adaptation to dry and aquatic habitats in Ceratocephala and Myosurus, respectively. Moreover, intensified aridity and frequent sea-level fluctuations, as well as global cooling, might have favored an increased rate of change in some genes at about 3.3 Ma, associated with adaptation to dry and aquatic environments, respectively. These findings suggest that changing environments might have influenced structural variations of plastomes and fixed new mutations arising on some plastid genes owing to adaptation to specific habitats.

Correlation-Induced Symmetry-Broken States in Large-Angle Twisted Bilayer Graphene on MoS2.

Strongly correlated states commonly emerge in twisted bilayer graphene (TBG) with "magic-angle" (1.1°), where the electron-electron (e-e) interaction U becomes prominent relative to the small bandwidth W of the nearly flat band. However, the stringent requirement of this magic angle makes the sample preparation and the further application facing great challenges. Here, using scanning tunneling microscopy (STM) and spectroscopy (STS), we demonstrate that the correlation-induced symmetry-broken states can also be achieved in a 3.45° TBG, via engineering this nonmagic-angle TBG into regimes of U/W > 1. We enhance the e-e interaction through controlling the microscopic dielectric environment by using a MoS2 substrate. Simultaneously, the width of the low-energy van Hove singularity (VHS) peak is reduced by enhancing the interlayer coupling via STM tip modulation. When partially filled, the VHS peak exhibits a giant splitting into two states flanked by the Fermi level and shows a symmetry-broken LDOS distribution with a stripy charge order, which confirms the existence of strong correlation effect in our 3.45° TBG. Our result demonstrates the feasibility of the study and application of the correlation physics in TBGs with a wider range of twist angle.

Twist-Angle Tuning of Electronic Structure in Two-Dimensional Dirac Nodal Line Semimetal Au2Ge on Au(111).

Topological semimetals have emerged as quantum materials including Dirac, Weyl, and nodal line semimetals, and so on. Dirac nodal line (DNL) semimetals possess topologically nontrivial bands crossing along a line or a loop and are considered precursor states for other types of semimetals. Here, we combine scanning tunneling microscopy/spectroscopy (STM/S) measurements and density functional theory (DFT) calculations to investigate a twist angle tuning of electronic structure in two-dimensional DNL semimetal Au2Ge. Theoretical calculations show that two bands of Au2Ge touch each other in Γ-M and Γ-K paths, forming a DNL. A significant transition of electronic structure occurs by tuning the twist angle from 30° to 24° between monolayer Au2Ge and Au(111), as confirmed by STS measurements and DFT calculations. The disappearing of DNL state is a direct consequence of symmetry breaking.

circ_UTRN inhibits ferroptosis of ARJ21 cells to attenuate acute pancreatitis progression by regulating the miR-760-3p/FOXO1/GPX4 axis.

Aim: To explore the function of circ_UTRN in acute pancreatitis (AP). Methods: After exposing AR42J cells to caerulein, the levels of circ_UTRN, miR-760-3p, and glutathione peroxidase 4 (GPX4) were determined by quantitative polymerase chain reaction. Additionally, GPX4 and forkhead box O1 (FOXO1) protein levels were assessed by western blot. The levels of oxidative stress and ferroptosis in the supernatant of the treated AR42J cells were also assessed using commercial kits. Results: circ_UTRN inhibited caerulein-induced oxidative stress and ferroptosis by binding with miR-760-3p. Additionally, miR-760-3p directly targeted FOXO1, thereby regulating GPX4 levels. Furthermore, GPX4 knockdown abolished the effect of miR-760-3p downregulation in AP. Conclusion: circ_UTRN inhibited oxidative stress and ferroptosis by regulating the miR-760-3p/FOXO1/GPX4 axis. This is a potential new treatment strategy for AP.

Mitochondrial dynamics and colorectal cancer biology: mechanisms and potential targets.

Colorectal cancer (CRC) is a significant public health concern, and its development is associated with mitochondrial dysfunction. Mitochondria can adapt to the high metabolic demands of cancer cells owing to their plasticity and dynamic nature. The fusion-fission dynamics of mitochondria play a crucial role in signal transduction and metabolic functions of CRC cells. Enhanced mitochondrial fission promotes the metabolic reprogramming of CRC cells, leading to cell proliferation, metastasis, and chemoresistance. Excessive fission can also trigger mitochondria-mediated apoptosis. In contrast, excessive mitochondrial fusion leads to adenosine triphosphate (ATP) overproduction and abnormal tumor proliferation, whereas moderate fusion protects intestinal epithelial cells from oxidative stress-induced mitochondrial damage, thus preventing colitis-associated cancer (CAC). Therefore, an imbalance in mitochondrial dynamics can either promote or inhibit CRC progression. This review provides an overview of the mechanism underlying mitochondrial fusion-fission dynamics and their impact on CRC biology. This revealed the dual role of mitochondrial fusion-fission dynamics in CRC development and identified potential drug targets. Additionally, this study partially explored mitochondrial dynamics in immune and vascular endothelial cells in the tumor microenvironment, suggesting promising prospects for targeting key fusion/fission effector proteins against CRC.

Correlations between multimodal neuroimaging and peripheral inflammation in different subtypes and mood states of bipolar disorder: a systematic review.

BACKGROUND: Systemic inflammation-immune dysregulation and brain abnormalities are believed to contribute to the pathogenesis of bipolar disorder (BD). However, the connections between peripheral inflammation and the brain, especially the interactions between different BD subtypes and episodes, remain to be elucidated. Therefore, we conducted the present study to provide a comprehensive understanding of the complex association between peripheral inflammation and neuroimaging findings in patients with bipolar spectrum disorders. METHODS: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42023447044) and conducted according to the Population, Intervention, Comparison, Outcomes, and Study Design (PICOS) framework. Online literature databases (PubMed, Web of Science, Scopus, EMBASE, MEDLINE, PsycINFO, and the Cochrane Library) were searched for studies that simultaneously investigated both peripheral inflammation-related factors and magnetic resonance neurography of BD patients up to July 01, 2023. Then, we analysed the correlations between peripheral inflammation and neuroimaging, as well as the variation trends and the shared and specific patterns of these correlations according to different clinical dimensions. RESULTS: In total, 34 publications ultimately met the inclusion criteria for this systematic review, with 2993 subjects included. Among all patterns of interaction between peripheral inflammation and neuroimaging, the most common pattern was a positive relationship between elevated inflammation levels and decreased neuroimaging measurements. The brain regions most susceptible to inflammatory activation were the anterior cingulate cortex, amygdala, prefrontal cortex, striatum, hippocampus, orbitofrontal cortex, parahippocampal gyrus, postcentral gyrus, and posterior cingulate cortex. LIMITATIONS: The small sample size, insufficiently explicit categorization of BD subtypes and episodes, and heterogeneity of the research methods limited further implementation of quantitative data synthesis. CONCLUSIONS: Disturbed interactions between peripheral inflammation and the brain play a critical role in BD, and these interactions exhibit certain commonalities and differences across various clinical dimensions of BD. Our study further confirmed that the fronto-limbic-striatal system may be the central neural substrate in BD patients.

The predictive value of sarcopenia and myosteatosis in trans-arterial (chemo)-embolization treated HCC patients.

BACKGROUND: We conducted a meta-analysis to provide evidence-based results for the predictive values of sarcopenia, skeletal muscle index, psoas muscle index and the myosteatosis regarding the impact of survival outcomes and tumor response in patients treated by trans-arterial (chemo)-embolization (TAE/TACE), thereby optimizing therapeutic strategies and maximizing clinical benefits for hepatocellular carcinoma patients. METHODS: Qualified studies were retrieved from PubMed, the Cochrane Library, EMBASE, and Google Scholar before June 19, 2023. We investigated the relationships between sarcopenia, SMI, PMI, myosteatosis, and the overall survival of TAE/TACE-treated hepatocellular carcinoma patients with pooling data. RESULTS: A total of 167 studies were collected and 12 studies were finally included for analysis. The meta-analysis assisted that the sarcopenia (HR: 1.46, 95% CI: 1.30-1.64, p < 0.001), skeletal muscle index (HR: 1.48, 95% CI: 1.29-1.69, p < 0.001), and psoas muscle index (HR: 1.45, 95% CI: 1.19-1.77, p < 0.001) were significantly related to a shorter OS of hepatocellular carcinoma patients who treated by TAE/TACE. Sarcopenia significantly contributed to a lower objective response rate of TAE/TACE treated hepatocellular carcinoma patients (OR: 0.80, 95% CI: 0.65-0.98, p = 0.032). But there was no significant association between the myosteatosis and the overall survival (HR: 1.29, 95% CI: 0.74-2.25, p = 0.366). Sensitivity analysis supported the stability and dependability of above analyses conclusions. CONCLUSION: Sarcopenia, skeletal muscle index and psoas muscle index, are significant prognostic predictors for TAE/TACE treated hepatocellular carcinoma patients. While myosteasis does not demonstrate a prognostic impact on the overall survival of TAE/TACE treated hepatocellular carcinoma patients.

Time-Sequential and Multi-Functional 3D Printed MgO2 /PLGA Scaffold Developed as a Novel Biodegradable and Bioactive Bone Substitute for Challenging Postsurgical Osteosarcoma Treatment.

Osteosarcoma (OS) is the most commonly occurring primary bone malignant tumor. The clinical postsurgical OS treatment faces big challenges for the staged therapeutic requirements of early anti-tumor, anti-bacterial, and long-lasting osteogenesis. Herein, multi-functional bioactive scaffolds with time-sequential functions of preventing tumor recurrence, inhibiting bacterial infection, and promoting bone defect repair are designed as a novel strategy. Nanocomposite scaffold magnesium peroxide (MgO2 )/poly (lactide-co-glycolide) is prepared by low-temperature 3D printing for controllable releasing magnesium ions (Mg2+ ) and reactive oxygen species in a time-sequential manner. The scaffold with 20 wt% MgO2 (20MP) is verified with desired mechanical properties, as well as exhibits staged release behavior of bioactive elements with hydrogen peroxide (H2 O2 ) release for the first 3 weeks, and long-lasting Mg2+ release for 12 weeks. The released H2 O2 initiates chemodynamic therapy to induce apoptosis and ferroptosis in tumor cells, along with activating the anticancer immune microenvironment by M1 polarization of macrophages. The released Mg2+ subsequently enhances bone repair by activating the Wnt3a/GSK-3ß/ß-catenin signaling pathway to promote osteogenic differentiation of bone marrow mesenchymal stem cells and create osteopromotive immune microenvironment by M2 polarization of macrophages. In conclusion, the multi-functional 20MP scaffold demonstrates time-sequential therapeutic properties as an innovative strategy for OS-associated bone defect treatment.

Understanding the Connection Among Ikigai, Well-Being, and Home Robot Acceptance in Japanese Older Adults: Mixed Methods Study.

BACKGROUND: Ikigai (meaning or purpose in life) is a concept understood by most older adults in Japan. The term has also garnered international attention, with recent academic attempts to map it to concepts in the Western well-being literature. In addition, efforts to use social and home robots to increase well-being have grown; however, they have mostly focused on hedonic well-being (eg, increasing happiness and decreasing loneliness) rather than eudaimonic well-being (eg, fostering meaning or purpose in life). OBJECTIVE: First, we explored how Japanese older adults experience ikigai and relate these to concepts in the Western well-being literature. Second, we investigated how a home robot meant to promote ikigai is perceived by older adults. METHODS: We used a mixed methods research design-including 20 interviews with older adults, a survey of 50 older adults, and 10 interviews with family caregivers. For interviews, we asked questions about older adults' sources of ikigai, happiness, and social support, along with their perception of the robot (QT). For surveys, a number of well-being scales were used, including 2 ikigai scales-ikigai-9 and K-1-and 6 Patient-Reported Outcomes Measurement Information System scales, measuring meaning and purpose, positive affect, satisfaction with participation in social roles, satisfaction with participation in discretionary social activities, companionship, and emotional support. Questions related to the perception and desired adoption of the robot and older adults' health status were also included. RESULTS: Our results suggest that health is older adults' most common source of ikigai. Additionally, although self-rated health correlated moderately with ikigai and other well-being measures, reported physical limitation did not. As opposed to social roles (work and family), we found that ikigai is more strongly related to satisfaction with discretionary social activities (leisure, hobbies, and friends) for older adults. Moreover, we found that older adults' sources of ikigai included the eudaimonic aspects of vitality, positive relations with others, contribution, accomplishment, purpose, and personal growth, with the first 3 being most common, and the hedonic aspects of positive affect, life satisfaction, and lack of negative affect, with the first 2 being most common. However, the concept of ikigai was most related to eudaimonic well-being, specifically meaning in life, along the dimension of significance. Finally, we found that Japanese older adults have high expectations of a home robot for well-being, mentioning that it should support them in a multitude of ways before they would likely adopt it. However, we report that those with the highest levels of meaning, and satisfaction with their leisure life and friendships, may be most likely to adopt it. CONCLUSIONS: We outline several ways to improve the robot to increase its acceptance, such as improving its voice, adding functional features, and designing it to support multiple aspects of well-being.

Two-Dimensional Artificial Ge Superlattice Confining in Electronic Kagome Lattice Potential Valleys.

Constructing two-dimensional (2D) artificial superlattices based on single-atom and few-atom nanoclusters is of great interest for exploring exotic physics. Here we report the realization of two types of artificial germanium (Ge) superlattice self-confined by a 37×37 R25.3° superstructure of bismuth (Bi) induced electronic kagome lattice potential valleys. Scanning tunneling microscopy measurements demonstrate that Ge atoms prefer to be confined in the center of the Bi electronic kagome lattice, forming a single-atom superlattice at 120 K. In contrast, room temperature grown Ge atoms and clusters are confined in the sharing triangle corner and the center, respectively, of the kagome lattice potential valleys, forming an artificial honeycomb superlattice. First-principle calculations and Mulliken population analysis corroborate that our reported atomically thin Bi superstructure on Au(111) has a kagome surface potential valley with the center of the inner Bi hexagon and the space between the outer Bi hexagons being energetically favorable for trapping Ge atoms.

Core-Sheath Fiber-Based Triboelectric Nanogenerators for Energy Harvesting and Self-Powered Straight-Arm Sit-Up Sensing.

Fiber-based triboelectric nanogenerators (F-TENGs), a green and sustainable energy-harvesting and transformation technology, hold great potential in the areas of portable energy harvesters and smart wearable sensors. Herein, the core-sheath structure F-TENGs (CF-TENGs) are developed by using continuous production equipment. The CF-TENGs, consisting of an elastic conductive fiber (core layer) and silicone rubber (sheath layer), can simultaneously accomplish stable reversible strain and excellent electrical output performance. High outputs (an open-circuit voltage of 17.5 V and a short-circuit current of 0.1 µA at a frequency of 1 Hz) can be attained when the CF-TENGs (a length of 5 cm) are contacted with a nylon fabric. The CF-TENGs not only act as self-powered sensors for applications in motion monitoring but also efficiently transfer mechanical energy into electric energy. As self-powered wearable sensors, the CF-TENGs can accurately indicate various human physiological movements. Moreover, they can be applied on straight-arm sit-up sensing to achieve standardized sport testing. Importantly, a CF-TENG-based weaved fabric presents high electrical performance to meet requirements as an energy harvester. These CF-TENGs provide a significant insight to facilitate the development of fiber-based triboelectric applications.

Tunable non-volatile memories based on 2D InSe/h-BN/GaSe heterostructures towards potential multifunctionality.

Floating-gate memories based on two-dimensional van der Waal (2D vdW) heterostructures play an important role in the development of next-generation information technology. The diversity of 2D vdW materials and their heterostructures provides flexibility in the design of novel storage architectures. However, 2D InSe/h-BN/GaSe heterostructures are rarely reported in the field of tunable non-volatile memories, probably due to the quality limitation of materials and complex interfaces from stackings. Herein, a floating-gate 2D InSe/h-BN/GaSe memory with high performance and atmosphere stability is demonstrated. It exhibits both a large ON/OFF current ratio of ∼105 and a good extinction ratio of ∼103, with an estimated maximum storage capacity of 5.1 × 1012 cm-2. Moreover, the storage performance can be regulated by optimizing the thickness of the insulating h-BN layer. Different device configurations have been explored to validate the working mechanism. Furthermore, a simulation of biological synaptic behavior is achieved on the same prototype device. The enhanced non-volatile characteristics enable the exploration of the integrated 2D memory and potential multifunctionality.

Realization of black phosphorus-like PbSe monolayer on Au(111) via epitaxial growth.

Lead selenide (PbSe) has been attracted a lot attention in fundamental research and industrial applications due to its excellent infrared optical and thermoelectric properties, toward reaching the two-dimensional limit. Herein, we realize the black phosphorus-like PbSe (α-phase PbSe) monolayer on Au(111) via epitaxial growth, where a characteristic rectangular superlattice of 5 Å × 9 Å corresponding to 1 × 2 reconstruction with respect to the pristine ofα-phase PbSe is observed by scanning tunneling microscopy. Corresponding density functional theory calculation confirmed the reconstruction and revealed the driven mechanism, the coupling between monolayer PbSe and Au(111) substrate. The metallic feature of differential conductance spectra as well as the transition of the density of states from semiconductor to metal further verified such coupling. As the unique anisotropic structure, our study provides a pathway towards the synthesis of BP-PbSe monolayer. In addition, it builds up an ideal platform for studying fundamental physics and also excellent prospects in PbSe-based device applications.

Regulation of Osteoimmune Microenvironment and Osteogenesis by 3D-Printed PLAG/black Phosphorus Scaffolds for Bone Regeneration.

The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid-co-glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2 polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid-associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K-AKT signaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.

[Construction of NKG2D CAR-NK92 cells and its killing effect on multiple myeloma cells].

Objective This study aims to construct and identify the chimeric antigen receptor NK92 (CAR-NK92) cells targeting NKG2D ligand (NKG2DL) (secreting IL-15Ra-IL-15) and verify the killing activity of NKG2D CAR-NK92 cells against multiple myeloma cells. Methods The extracellular segment of NKG2D was employed to connect 4-1BB and CD3Z, as well as IL-15Ra-IL-15 sequence to obtain a CAR expression framework. The lentivirus was packaged and transduced into NK92 cells to obtain NKG2D CAR-NK92 cells. The proliferation of NKG2D CAR-NK92 cells was detected by CCK-8 assay, IL-15Ra secretion was detected by ELISA and killing efficiency was detected by lactate dehydrogenase (LDH) assay. The molecular markers of NKp30, NKp44, NKp46, the ratio of apoptotic cell population, CD107a, and the secretion level of granzyme B and perforin were detected using flow cytometry. In addition, the cytotoxic mechanism of NKG2D CAR-NK92 cells on the tumor was verified by measuring the degranulation ability. Moreover, after NKG2D antibody inhibited effector cells and histamine inhibited tumor cells, LDH assay was utilized to detect the effect on cell-killing efficiency. Finally, the multiple myeloma tumor xenograft model was constructed to verify its anti-tumor activity in vivo. Results Lentiviral transduction significantly increased NKG2D expression in NK92 cells. Compared with NK92 cells, the proliferation ability of NKG2D CAR-NK92 cells was weaker. The early apoptotic cell population of NKG2D CAR-NK92 cells was less, and NKG2D CAR-NK92 cells had stronger cytotoxicity to multiple myeloma cells. Additionally, IL-15Ra secretion could be detected in its culture supernatant. NKp44 protein expression in NKG2D CAR-NK92 cells was clearly increased, demonstrating an enhanced activation level. Inhibition test revealed that the cytotoxicity of CAR-NK92 cells to MHC-I chain-related protein A (MICA) and MICB-positive tumor cells was more dependent on the interaction between NKG2D CAR and NKG2DL. After stimulating NKG2D CAR-NK92 cells with tumor cells, granzyme B and perforin expression increased, and NK cells obviously upregulated CD107α. Furthermore, multiple myeloma tumor xenograft model revealed that the tumors of mice treated with NKG2D CAR-NK92 cells were significantly reduced, and the cell therapy did not sensibly affect the weight of the mice. Conclusion A type of CAR-NK92 cell targeting NKG2DL (secreting IL-15Ra-IL-15) is successfully constructed, indicating the effective killing of multiple myeloid cells.