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Abstract Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.

Abstract Background Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. Results The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. Conclusions Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment. Graphical Abstract

Background Cushing’s syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters.Methods A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD.Results A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p

Abstract Graphene field‐effect transistors (GFETs) are widely used in biosensing due to their excellent properties in biomolecular signal amplification, exhibiting great potential for high‐sensitivity and point‐of‐care testing in clinical diagnosis. However, difficulties in complicated fabrication steps are the main limitations for the further studies and applications of GFETs. In this study, a modular fabrication technique is introduced to construct microfluidic GFET biosensors within 3 independent steps. The low‐melting metal electrodes and intricate flow channels are incorporated to maintain the structural integrity of graphene and facilitate subsequent sensing operations. The as‐fabricated GFET biosensor demonstrates excellent long‐term stability, and performs effectively in various ion environments. It also exhibits high sensitivity and selectivity for detecting single‐stranded nucleic acids at a 10 fm concentration. Furthermore, when combined with the CRISPR/Cas12a system, it facilitates amplification‐free and rapid detection of nucleic acids at a concentration of 1 fm. Thus, it is believed that this modular‐fabricated microfluidic GFET may shed light on further development of FET‐based biosensors in various applications.

Abstract Quasi‐2D perovskite quantum wells are increasingly recognized as promising candidates for direct‐conversion X‐ray detection. However, the fabrication of oriented and uniformly thick quasi‐2D perovskite films, crucial for effective high‐energy X‐ray detection, is hindered by the inherent challenges of preferential crystallization at the gas‐liquid interface, resulting in poor film quality. In addressing this limitation, a carbonyl array‐synergized crystallization (CSC) strategy is employed for the fabrication of thick films of a quasi‐2D Ruddlesden‐Popper (RP) phase perovskite, specifically PEA2MA4Pb5I16. The CSC strategy involves incorporating two forms of carbonyls in the perovskite precursor, generating large and dense intermediates. This design reduces the nucleation rate at the gas‐liquid interface, enhances the binding energies of Pb2+ at (202) and (111) planes, and passivates ion vacancy defects. Consequently, the construction of high‐quality thick films of PEA2MA4Pb5I16 RP perovskite quantum wells is achieved and characterized by vertical orientation and a pure well‐width distribution. The corresponding PEA2MA4Pb5I16 RP perovskite X‐ray detectors exhibit multi‐dimensional advantages in performance compared to previous approaches and commercially available a‐Se detectors. This CSC strategy promotes 2D perovskites as a candidate for next‐generation large‐area flat‐panel X‐ray detection systems.

Abstract High performance X-ray detector with ultra-high spatial and temporal resolution are crucial for biomedical imaging. This study reports a dynamic direct-conversion CMOS X-ray detector assembled with screen-printed CsPbBr3, whose mobility-lifetime product is 5.2 × 10−4 cm2 V–1 and X-ray sensitivity is 1.6 × 104 µC Gyair –1 cm–2. Samples larger than 5 cm $$\times$$ × 10 cm can be rapidly imaged by scanning this detector at a speed of 300 frames per second along the vertical and horizontal directions. In comparison to traditional indirect-conversion CMOS X-ray detector, this perovskite CMOS detector offers high spatial resolution (5.0 lp mm−1) X-ray radiographic imaging capability at low radiation dose (260 nGy). Moreover, 3D tomographic images of a biological specimen are also successfully reconstructed. These results highlight the perovskite CMOS detector’s potential in high-resolution, large-area, low-dose dynamic biomedical X-ray and CT imaging, as well as in non-destructive X-ray testing and security scanning.

The measurement of cardiac troponin I (cTnI) is of vital importance for the early diagnosis of acute myocardial infarction. In this study, an enhanced electrochemiluminescent immunoassay for the highly sensitive and precise determination of cTnI was reported. A biomimetic chip with nepenthes peristome surface microstructures to achieve single-layer microbead arrays and integrated microelectrode arrays (MEAs) for ECL detection was microfabricated. Ru@SiO2 nanoparticles were prepared as signal amplificators labeling immunomagnetic beads. Dendrimer-encapsulated platinum nanoparticles (Pt DENs) were electrochemically modified on ITO MEAs. The resulting Pt DEN-modified ITO MEAs preserved good optical transparency and exhibited an approximately 20-fold ECL signal amplification compared to that obtained from bare ITO. The method made full use of the biomimetic chip with Pt DENs to develop single-layer immunomagnetic bead arrays with increasingly catalyzed electrochemical oxidation of the [Ru(bpy)3]2+–TPA system. Consequently, a limit of detection calculated as 0.38 pg/mL (S/N = 3) was obtained with excellent selectivity, demonstrating significant potential for the detection of cTnI in clinical diagnostics.

Abstract Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB−/− bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.

Abstract As a common tumor with high incidence, osteosarcoma possesses extremely poor prognosis and high mortality. Improving the survival of osteosarcoma patients is still a great challenge due to the precipice of advancement in treatment. In this study, a combination strategy of gene therapy and photothermal therapy (PTT) is developed for efficient treatment of osteosarcoma. Two-dimensional (2D) FePS3 nanosheets are synthesized and functionalized by poly-L-lysine-PEG-folic acid (PPF) to fabricate a multifunctional nanoplatform (FePS@PPF) for further loading microRNAs inhibitor, miR-19a inhibitor (anti-miR-19a). The photothermal conversion efficiency of FePS@PPF is up to 47.1% under irradiation by 1064 nm laser. In vitro study shows that anti-miR-19a can be efficiently internalized into osteosarcoma cells through the protection and delivery of FePS@PPF nanaocarrier, which induces up-regulation of PTEN protein and down-regulation p-AKT protein. After intravenous injection, the FePS@PPF nanoplatform specifically accumulates to tumor site of osteosarcoma-bearing mice. The in vitro and in vivo investigations reveal that the combined PTT-gene therapy displays most significant tumor ablation compared with monotherapy. More importantly, the good biodegradability promotes FePS@PPF to be cleared from body avoiding potential toxicity of long-term retention. Our work not only develops a combined strategy of NIR-II PTT and gene therapy mediated by anti-miR-19a/FePS@PPF but also provides insights into the design and applications of other nanotherapeutic platforms.

This article presents a comprehensive review of the factors influencing the efficacy of mesenchymal stem cells (MSCs) transplantation and its association with platelet concentrates (PCs). It focuses on investigating the impact of PCs’ composition, the age and health status of platelet donors, application methods, and environmental factors on the outcomes of relevant treatments. In addition, it delves into the strategies and mechanisms for optimizing MSCs transplantation with PCs, encompassing preconditioning and combined therapies. Furthermore, it provides an in-depth exploration of the signaling pathways and proteomic characteristics associated with preconditioning and emphasizes the efficacy and specific effects of combined therapy. The article also introduces the latest advancements in the application of biomaterials for optimizing regenerative medical strategies, stimulating scholarly discourse on this subject. Through this comprehensive review, the primary goal is to facilitate a more profound comprehension of the factors influencing treatment outcomes, as well as the strategies and mechanisms for optimizing MSCs transplantation and the application of biomaterials in regenerative medicine, offering theoretical guidance and practical references for related research and clinical practice.

Abstract The photothermal performance of black phosphorus (BP) in the near infrared (NIR)‐II bio‐window (1000–1500 nm) is low, which limits its biomedical applications. Herein, ultrasmall nickel phosphide quantum dots (Ni2P QDs) are synthesized with BP quantum dots (BPQDs) as the template by topochemical transformation. The size of Ni2P QDs is ≈3.5 nm, similar to that of BPQDs, whereas the absorption and photothermal conversion efficiency of Ni2P QDs at 1064 nm (43.5%) are significantly improved compared with those of BPQDs. To facilitate in vivo applications, an Ni2P QDs‐based liposomal nano‐platform (Ni2P‐DOX@Lipo‐cRGD) is designed by incorporation of Ni2P QDs and doxorubicin (DOX) into liposomal bilayers and the interior, respectively. The encapsulated DOX is responsively released from liposomes upon 1064‐nm laser irradiation owing to the photothermal effect of Ni2P QDs, and the drug release rate and amount are controlled by the light intensity and exposure time. In vivo, experiments show that Ni2P‐DOX@Lipo‐cRGD has excellent tumor target capability and biocompatibility, as well as complete tumor ablation through the combination of photothermal therapy and chemotherapy. The work provides a new paradigm for the NIR‐II transformation of nano‐materials and may shed light on the construction of multifunctional nano‐platforms for cancer treatment.

The challenge of data-driven synthesis of advanced nanomaterials can be minimized by using machine learning algorithms to optimize synthesis parameters and expedite the innovation process. In this study, a high-throughput robotic platform was employed to synthesize over 1356 gold nanorods with varying aspect ratios via a seedless approach. The developed models guided us in synthesizing gold nanorods with customized morphology, resulting in highly repeatable morphological yield with quantifiable structure-modulating precursor adjustments. The study provides insight into the dynamic relationships between key structure-modulating precursors and the structural morphology of gold nanorods based on the expected aspect ratio. The high-throughput robotic platform-fabricated gold nanorods demonstrated precise aspect ratio control when spectrophotometrically investigated and further validated with the transmission electron microscopy characterization. These findings demonstrate the potential of high-throughput robot-assisted synthesis and machine learning in the synthesis optimization of gold nanorods and aided in the development of models that can aid such synthesis of as-desired gold nanorods.

Abstract 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.

Abstract Although perovskite nanocrystals have attracted considerable interests as emerging semiconductors in optoelectronic devices, design and fabrication of a deformable structure with high stability and flexibility while meeting the charge transport requirements remain a huge challenge. Herein, a combined soft‐hard strategy is demonstrated to fabricate intrinsically flexible all‐inorganic perovskite layers for photodetection via ligand cross‐linking. Perfluorodecyltrichlorosilane (FDTS) is employed as the capping ligand and passivating agent bound to the CsPbBr3 surface via Pb‐F and Br‐F interactions. The SiCl head groups of FDTS are hydrolyzed to produce SiOH groups which subsequently condense to form the SiOSi network. The CsPbBr3@FDTS nanocrystals (NCs) are monodispersed cubes with an average particle size of 13.03 nm and exhibit excellent optical stability. Furthermore, the residual hydroxyl groups on the surface of the CsPbBr3@FDTS render the NCs tightly packed and cross‐linked to each other to form a dense and elastic CsPbBr3@FDTS film with soft and hard components. The photodetector based on the flexible CsPbBr3@FDTS film exhibits outstanding mechanical flexibility and robust stability after 5000 bending cycles.

Abstract Owing to increasing global demand for carbon neutral and fossil‐free energy systems, extensive research is being conducted on efficient and inexpensive electrocatalysts for catalyzing the kinetically sluggish oxygen reduction reaction (ORR) at the cathode of fuel cells. Platinum (Pt)‐based alloys are considered promising candidates for replacing expensive Pt catalysts. However, the current screening process of Pt‐based alloys is time‐consuming and labor‐intensive, and the descriptor for predicting the activity of Pt‐based catalysts is generally inaccurate. This study proposed a strategy by combining high‐throughput first‐principles calculations and machine learning to explore the descriptor used for screening Pt‐based alloy catalysts with high Pt utilization and low Pt consumption. Among the 77 prescreened candidates, we identified 5 potential candidates for catalyzing ORR with low overpotential. Furthermore, during the second and third rounds of active learning, more Pt‐based alloys ORR candidates are identified based on the relationship between structural features of Pt‐based alloys and their activity. In addition, we highlighted the role of structural features in Pt‐based alloys and found that the difference between the electronegativity of Pt and heteroatom, the valence electrons number of the heteroatom, and the ratio of heteroatoms around Pt are the main factors that affect the activity of ORR. More importantly, the combination of those structural features can be used as structural descriptor for predicting the activity of Pt‐based alloys. We believe the findings of this study will provide new insight for predicting ORR activity and contribute to exploring Pt‐based electrocatalysts with high Pt utilization and low Pt consumption experimentally.

Background: Stickler syndrome (SS) is a group of hereditary collagenopathies caused by a variety of collagen and non-collagen genes. Affected patients have characteristic manifestations involving ophthalmic, articular, craniofacial and auditory disorders. SS is classified into several subtypes according to clinical and molecular features. Type 3 SS is an ultra-rare disease, known as non-ocular SS or otospondylomegaepiphyseal dysplasia (OSMED) with only a few pathogenic COL11A2 variants reported to date.Case presentation: A 29-year-old Chinese male was referred to our hospital for hearing loss and multiple joint pain. He presented a phenotype highly suggestive of OSMED, including progressive sensorineural deafness, spondyloepiphyseal dysplasia with large epiphyses, platyspondyly, degenerative osteoarthritis, and sunken nasal bridge. We detected compound heterozygous mutations in COL11A2, both of which were predicted to be splicing mutations. One is synonymous mutation c.3774C>T (p.Gly1258Gly) supposed to be a splice site mutation, the other is a novel intron mutation c.4750 + 5 G>A, which is a highly conservative site across several species. We also present a review of the current known pathogenic mutation spectrum of COL11A2 in patients with type 3 SS.Conclusion: Both synonymous extonic and intronic variants are easily overlooked by whole-exome sequencing. For patients with clinical manifestations suspected of SS syndrome, next-generation whole-genome sequencing is necessary for precision diagnosis and genetic counseling.

Abstract Although perovskite wafers with a scalable size and thickness are suitable for direct X‐ray detection, polycrystalline perovskite wafers have drawbacks such as the high defect density, defective grain boundaries, and low crystallinity. Herein, PbI2‐DMSO powders are introduced into the MAPbI3 wafer to facilitate crystal growth. The PbI2 powders absorb a certain amount of DMSO to form the PbI2‐DMSO powders and PbI2‐DMSO is converted back into PbI2 under heating while releasing DMSO vapor. During isostatic pressing of the MAPbI3 wafer with the PbI2‐DMSO solid additive, the released DMSO vapor facilitates in situ growth in the MAPbI3 wafer with enhanced crystallinity and reduced defect density. A dense and compact MAPbI3 wafer with a high mobility‐lifetime (µτ) product of 8.70 × 10−4 cm2 V−1 is produced. The MAPbI3‐based direct X‐ray detector fabricated for demonstration shows a high sensitivity of 1.58 × 104 µC Gyair−1 cm−2 and a low detection limit of 410 nGyair s−1.

Jiaodong is the largest gold deposit concentration area in China. In recent years, great breakthroughs have been made in deep prospecting, and it has become the third largest concentration area of gold deposits in the world. A series of prospecting discoveries in the Jiaodong area provided the basic conditions for summarizing the regional metallogenic law, constructing the deposit model, carrying out research on the genesis of the deposit and innovating metallogenic theory. The Jiaodong gold deposits are mainly distributed in Northwest Jiaodong, Qi-Peng-Fu and Mu-Ru metallogenic regions, and mainly occur in Precambrian metamorphic rock series, Jurassic Linglong-type granite, Early Cretaceous Guojialing-type granite and Laiyang group. The orebodies are controlled by Sanshandao, Jiaojia, Zhaoping, Xilin-Douya, Jinniushan and other major ore-controlling fault zones. The main mineralization types include altered rock-type, quartz vein-type, stockwork type, sulfide quartz vein-type, interlayer detachment zone-type, altered conglomerate-type, basin margin fault breccia-type and pyrite carbonate vein-type and so on. The important progress of deep prospecting is summarized: two super giant deposits have been evaluated in the Sanshandao and Jiaojia areas; the amount of altered rock-type gold resources identified by deep prospecting has exceeded that of quartz vein-type gold deposits in the Linglong gold deposit field; the Hushan large scale gold deposit has been discovered in Qixia gold deposit field; and the Liaoshang large-size gold deposit is a new discovery of deep prospecting in Pengjiakuang gold deposit field. The ore-controlling faults of gold deposits have several changing steps with dip angle varying from steep to gentle along the dip angle. The gold ore bodies are mainly enriched in sections along the steep, gentle turning points and relatively gentle parts of the fault dip angle, forming a stepped distribution pattern. In the Early Cretaceous, the subduction and rollback of the Paleo-Pacific plate induced crust mantle interaction, resulting in large-scale magmatic and fluid activities. The crust tension and magma uplift form the dome extension structure of granite, which provides a channel for the migration of ore-forming fluid and also provides favorable space for the deposition of ore-forming fluid.

Hematological malignancies encompass a wide variety of severe diseases that pose a serious threat to human health. Given the fact that hematological malignancies are difficult to treat due to their unpredictable and rapid deterioration and high rates of recurrence, growing attention has been paid to their early screening and diagnosis. However, developing a rapid and effective diagnostic tool featuring a noninvasive sampling technique is still extremely challenging. In recent years, novel nanomaterials-based electrochemical biosensors have attracted great interest because of such advantages as simple operation, low cost, fast response, etc. As a kind of rising nanomaterials, two-dimensional materials have excellent electronic and chemical properties, which have been proven to improve the performance of electrochemical biosensors. This review summarizes the applications of different types of electrochemical biosensors (nucleic acid sensors, immunosensors, aptamer biosensors, and cytosensors) based on two-dimensional materials in the detection of biological molecules related to hematological malignancies. Two-dimensional materials-based electrochemical biosensors designed for the diagnosis of leukemia could rapidly detect the target biomolecules at a trace level and show great merits such as wide linear range, low detection limit, high sensitivity, excellent selectivity, and cost-effectiveness. In addition, these biosensors have also achieved satisfactory results in the diagnosis of lymphoma and multiple myeloma. Thus, two-dimensional materials-based electrochemical biosensors are attractive for the early diagnosis of hematological malignancies in clinical practice. Nevertheless, more efforts are still required to further improve the performance of electrochemical biosensors. In this review, we propose the possible main concerns in the design of future two-dimensional materials-based electrochemical biosensors, involving the development of sensors for synchronous detection of diverse target biomolecules, the exploration of other superior two-dimensional materials, the simplification of the sensors fabrication process, the construction of new hybrid structures and how to avoid possible environmental issues.

Abstract Background Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare form of adrenal Cushing’s syndrome. The slowly progressing expansion of bilateral adrenal tissues usually persists for dozens of years, leading to delayed onset with severe conditions due to chronic mild hypercortisolism. About 20–50% cases were found to be caused by inactivating mutation of armadillo repeat-containing protein 5 (ARMC5) gene. Case presentation A 51-year-old man was admitted for severe diabetes mellitus, resistant hypertension, centripedal obesity and edema. PBMAH was diagnosed after determination of adrenocorticotropic hormone and cortisol levels, dexamethasone suppression tests and abdominal contrast-enhanced CT scanning. The metabolic disorders of the patient remarkably improved after sequentially bilateral laparoscopic adrenalectomy combined with hormone replacement. Sanger sequencing showed germline nonsense mutation of ARMC5 c.967C>T (p.Gln323Ter). The second somatic missense mutation of ARMC5 was detected in one out of two resected nodules, reflecting the second-hit model of tumorigenesis. Routine genetic testing in his apparently healthy offspring showed one of two daughters and one son harbored the germline mutation. Conclusions In conclusion, our case report highlight the importance of genetic testing in the molecular diagnosis of PBMAH. Genetic screening in related family members will find out asymptomatic variant carriers to guide life-long follow-up.

The superior optical properties of lead-halide perovskites (LHPs) inspired significant research in cell imaging applications; many encapsulating processes have improved perovskite stabilities with comparable biosafety. Herein, facile solvent evaporation encapsulation based on an oil-in-fluorine emulsion for aqueous-stable and extremely nontoxic LHP microcapsules is described. Perfluorooctane dispersed the emulsifier fluorocarbon surfactant to form a continuous fluorine phase, while LHPs and polymethylmethacrylate (PMMA) were dispersed in 1,2-dichloroethane, then emulsified in the fluorine phase to form an oil-in-fluorine emulsion. CsPbBr3 microcapsules with a dense PMMA shell that protect fragile CsPbBr3 from the external environment and inhibit lead ion release were obtained after solvent evaporation. The CsPbBr3 microcapsules not only retained 91% of fluorescence intensity after exposure to water for 30 d but also possess extremely low cytotoxicity for MCF-7 cells. After exposure to 2 mg/mL of CsPbBr3 microcapsules for 48 h, the cell viability remained >90%. The intracellular uptake of CsPbBr3 microcapsules indicates its potential use in cell imaging.

Abstract Gastric cancer is one of the most common cancers globally and has a poor prognosis. MiR‐936 has been reported to regulate cell activity and tumor progression in non‐small cell lung cancer, glioma, and epithelial ovarian cancer. However, the specific role and mechanism of miR‐936 in gastric cancer have not been explored. In present study, gastric cancer cells were transfected with miR‐936 mimic, and cell proliferation, cell cycle distribution, cell apoptosis, migration and invasion were assessed via cell‐counting kit‐8, flow cytometry, wound healing, and transwell assay, respectively. Dual luciferase reporter assay was used to check miR‐936 binding to its downstream target. It was shown that miR‐936 was downregulated in gastric cancer tissues and cells. Erb‐B2 Receptor Tyrosine Kinase 4 (ERBB4) was confirmed as a direct target of miR‐936 and negatively regulated its expression by miR‐936. Overexpression of miR‐936 suppressed cell proliferation, cell cycle progression, cell migration and invasion, and enhanced cell apoptosis in gastric cancer cells, which could be reversed by further ERBB4 overexpression. Western blot results showed that miR‐936/ERBB4 axis regulated Akt‐related pathways to control gastric cancer cell activities. Therefore, our data suggest that miR‐936 overexpression inhibits cell proliferation and invasion and promotes cell apoptosis through Akt‐related pathways by targeting ERBB4, which provides novel insight to target miR‐936 or miR‐936/ERBB4 axis for the treatment of gastric cancer.

ABSTRACT: Recently, continuous breakthroughs have been made about deep gold prospecting in the Jiaodong gold province area of China. Approximately 5000 t of cumulative gold resources have been explored in Jiaodong, which has thus become an internationally noteworthy gold ore cluster. The gold exploration depth has been increased to about 2000 m from the previous

Abstract Chemodynamic therapy (CDT) is an emerging treatment that usually employs chemical agents to decompose hydrogen peroxide (H2O2) into hydroxyl radical (•OH) via Fenton or Fenton‐like reactions, inducing cell apoptosis or necrosis by damaging biomacromolecules such as, lipids, proteins, and DNA. Generally, CDT shows high tumor‐specificity and minimal‐invasiveness in patients, thus it has attracted extensive research interests. However, the catalytic reaction efficiency of CDT is largely limited by the relatively high pH at the tumor sites. Herein, a 808 nm laser‐potentiated peroxidase catalytic/mild‐photothermal therapy of molybdenum diphosphide nanorods (MoP2 NRs) is developed to improve CDT performance, and simultaneously achieve effective tumor eradication and anti‐infection. In this system, MoP2 NRs exhibit a favorable cytocompatibility due to their inherent excellent elemental biocompatibility. Upon irradiation with an 808 nm laser, MoP2 NRs act as photosensitizers to efficiently capture the photo‐excited band electrons and valance band holes, exhibiting enhanced peroxidase‐like catalytic activity to sustainedly decompose tumor endogenous H2O2 to •OH, which subsequently destroy the cellular biomacromolecules both in tumor cells and bacteria. As demonstrated both in vitro and in vivo, this system exhibits a superior therapeutic efficiency with inappreciable toxicity. Hence, the work may provide a promising therapeutic technique for further clinical applications.

The antifogging coating based on super-hydrophilic polymer is regarded as the most promising strategy to avoid fogging but suffers from short-term effectiveness due to antifogging failure induced by water invasion. In this study, a black phosphorus nanosheets (BPs) hybrid polymer hetero-network coating (PUA/PAHS/BPs HN) was prepared by UV curing for the first time to achieve long-term antifogging performance. The polymer hetero-network (HN) structure was composed of two novel cross-linked acrylic resin and polyurethane acrylate. Different from physical blending, a covalent P-C bond between BPs and polymer is generated by UV initiated free radical reaction, resulting in BPs firmly embedded in the polymer HN structure. The BPs enriched on the coating surface by UV regulating migration prevent permeation of water towards the inside of the coating through its own good water-based lubricity and water absorption capacity. Compared with the nonhybrid polymer HN, PUA/PAHS/BPs HN not only has higher hardness and better friction resistance properties, but also exhibits superior water resistance and longer antifogging duration. Since water invasion was greatly reduced by BPs, the PUA/PAHS/BPs HN coating maintained antifogging duration for 60 min under a 60 °C water vapor test and still maintained long-term antifogging performance after being immersed in water for 5 days.

A flexible all-solid-state supercapacitor with fast charging speed and high power density is a promising high-performance energy storage and sensor device in photovoltaic systems. Two-dimensional black phosphorus (BP) is a prospective electrode nanomaterial, but it struggles to fully exert its properties limited by its self-stacking. Herein, by embedding carbon nanoparticles into the interlayer of BP microplates, the designed BP/carbon nanoframe (BP/C NF) forms a certain nano-gap on the substrate for promoting the orderly transport of charges. The corresponding supercapacitor BP/C SC has a capacity of 372 F g−1, which is higher than that constructed from BP microplates (32.6 F g−1). Moreover, the BP/C SC exhibits good stability with a ca. 90% of capacitance retentions after 10,000 repeated bending and long-term cycles. Thus, the proposed strategy of using BP/carbon nanoframes is feasible to develop exceptional flexible energy devices, and it can guide the design of relevant two-dimensional nanocomposites.

Fluorescent imaging combined with atomic force microscopy (AFM), namely AFM-fluorescence correlative microscopy, is a popular technology in life science. However, the influence of involved fluorophores on obtained mechanical information is normally underestimated, and such subtle changes are still challenging to detect. Herein, we combined AFM with laser light excitation to perform a mechanical quantitative analysis of a model membrane system labeled with a commonly used fluorophore. Mechanical quantification was additionally validated by finite element simulations. Upon staining, we noticed fluorophores forming a diffuse weakly organized overlayer on phospholipid supported membrane, easily detected by AFM mechanics. The laser was found to cause a degradation of mechanical stability of the membrane synergically with presence of fluorophore. In particular, a 30 min laser irradiation, with intensity similar to that in typical confocal scanning microscopy experiment, was found to result in a ∼40% decrease in the breakthrough force of the stained phospholipid bilayer along with a ∼30% reduction in its apparent elastic modulus. The findings highlight the significance of analytical power provided by AFM, which will allow us to “see” the “unseen” in correlative microscopy, as well as the necessity to consider photothermal effects when using fluorescent dyes to investigate, for example, the deformability and permeability of phospholipid membranes.

Abstract Black phosphorus (BP) constitutes a new class of two‐dimensional materials with multiple biomedical functionalities and applications. Possessed with outstanding advantages of large surface area, intrinsic photoacoustic properties, excellent biocompatibility, and selective toxicity to tumor cells, BP is becoming an ideal candidate in multifunctional cancer theranostics including photothermal therapy, photodynamic therapy, drug delivery, and bioactive phosphotherapy. This minireview summarizes recent progress pertaining to theranostic applications of BP nanosheets and black phosphorus quantum dots and discusses the prospects in advanced theranostics.

Nanomechanics of cytoskeleton is deeply involved in physiology and regulation of cell behavior. Atomic Force Microscopy has been extensively used for quantitative characterization with high-spatial resolution, in particular showing tremendous opportunities in biomechanics by quantifying mechanical parameters related to cytoskeleton organization. In this short review, we highlight recent developments in cell nanomechanics by AFM focusing on methodology and direct application to investigate cytoskeleton restructuration when cells are interacting with nanostructures (surfaces and nanoparticles). In particular, cells can sense the stiffness of environment or internalized particles and AFM can detect the rearrangement of cytoskeleton as one of the responses of mechanotransduction stimuli. Current bottlenecks hindering further progress in technology, such as theoretical models of interpretation will be discussed, in particular we propose a solution for complex system by coupling AFM with finite element simulations to retrieve more quantitative information when heterogeneity and convolution play important roles. Finally, we present recent cutting-edge research directions to explore new techniques and enhance the capabilities of AFM nanomechanics for living cells.

Air pollution caused by acid gases (NO2, SO2) or greenhouse gases (CO2) is an urgent environmental problem. Two-dimensional nanomaterials exhibit exciting application potential in air pollution control, among which layered black phosphorus (LBP) has superior performance and is environmentally friendly. However, the current interaction mechanism of LBP with hazardous gases is contradictory to experimental observations, largely impeding development of LBP-based air pollution control nanotechnologies. Here, interaction mechanisms between LBP and hazardous gases are unveiled based on density functional theory and experiments. Results show that NO2 is different from other gases, as it can react with unsaturated defects of LBP, resulting in oxidation of LBP and reduction of NO2. Computational results indicate that the redox is initiated by p orbital hybridization between one oxygen atom of NO2 and the phosphorus atom carrying a dangling single electron in a defect’s center. For NO, the interaction mechanism is chemisorption on unsaturated LBP defects, whereas for SO2, NH3, CO2 or CO, the interaction is dominated by van der Waals forces (57–82% of the total interaction). Experiments confirmed that NO2 can oxidize LBP, yet other gases such as CO2 cannot. This study provides mechanistic understanding in advance for developing novel nanotechnologies for selectively monitoring or treating gas pollutants containing NO2.

Abstract The photochemical activity of black phosphorus (BP) in near‐infrared (NIR) light controlled in situ biomineralization is investigated. Owing to the excellent NIR absorption, irradiation with NIR light not only promotes degradation of BP into PO43−, but also enhances the chemical activity to accelerate the reaction between PO43− and Ca2+ and promote in situ biomineralization. Mineralization of hydrogels is demonstrated by the preparation of BP incorporated hydrogel (BP@Hydrogel) which delivers greatly improved biomineralization performance under NIR illumination. The biomineralization process which can be controlled by modulating the light irradiation time and location has a high potential in controlling the mechanical properties and osteoinductive ability in tissue engineering. This study also provides insights into the degradation, photochemical activity, and new biological/biomedical applications of BP.

Isothermal DNA amplification techniques are useful for diagnostic applications in place of traditional PCR. Here the authors describe CRISDA, which combines CRISPR–Cas9 with strand displacement amplification and exhibits attomolar sensitivity and single-nucleotide specificity in DNA detection.

A carrier-free CRISPR/Cas9 ribonucleoprotein delivery strategy for genome editing mediated by a cold atmospheric plasma (CAP) is described. The CAP is promising in many biomedical applications due to efficient production of bioactive ionized species. The MCF-7 cancer cells after CAP exposure exhibit increased extracellular reactive oxygen and nitrogen species (RONS) and altered membrane potential and permeability. Hence, transmembrane transport of Ca2+ into the cells increases and accelerates ATP hydrolysis, resulting in enhanced ATP-dependent endocytosis. Afterwards, the increased Ca2+ and ATP contents promote the release of cargo into cytoplasm due to the enhanced endosomal escape. The increased membrane permeability also facilitates passive diffusion of foreign species across the membrane into the cytosol. After CAP exposure, the MCF-7 cells incubated with Cas9 ribonucleoprotein (Cas9-sgRNA complex, Cas9sg) with a size of about 15 nm show 88.9% uptake efficiency and 65.9% nuclear import efficiency via passive diffusion and ATP-dependent endocytosis pathways. The efficient transportation of active Cas9sg after the CAP treatment leads to 21.7% and 30.2% indel efficiencies in HEK293T and MCF-7 cells, respectively. This CAP-mediated transportation process provides a simple and robust alternative for the delivery of active CRISPR/Cas9 ribonucleoprotein. Additionally, the technique can be extended to other macro-biomolecules and nanomaterials to cater to different biomedical applications.

Abstract The Sanshandao gold deposit contains an estimated Au resource of >1500 tons, however little is known about the history of exhumation, and the magnitude of displacement on the ore-hosting fault. Structural measurement revealed two phases of normal and one phase of sinistral movement on the fault. Despite of intra-sample dispersions, (U-Th)/He ages from two sub-vertical profiles show decreasing trends from the surface down to −3560 m (zircon: 123 Ma to 55 Ma; apatite 103 Ma to 0.3 Ma). Over-dispersion of AHe ages likely reflects the presence of undetected inclusions. According to the age-depth pattern, we infer that the deposit underwent an early phase of rapid cooling in the late Early Cretaceous, which was followed by a short period of thermal stagnation and a revived rapid cooling between 75 Ma and 55 Ma in response to a combined effects of late normal movement and erosion. Since the Eocene, the deposit has experienced a slow monotonic cooling. Exhumation magnitude estimates suggest that the deposit have been denudated > 5.1 km. The two phases of normal displacement along the fault occurred in the late Early Cretaceous and Late Cretaceous to Paleocene, leading to a total offset magnitude of 0.5–2.3 km.

Black phosphorus: a two-dimensional reductant Synthesis of various nano-sized materials generally involves chemical reduction with an extrinsic reductant. Here Prof. Xuefeng Yu, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, and co-workers have uncovered the reducing capability of black phosphorus (BP), a new 2D semiconductor material. It is demonstrated that the high reducing ability and unique 2D morphology of BP not only facilitate in situ synthesis of Au nanoparticles and BP@Au nanocomposites, but also enable multiscale control in local reduction of a graphene oxide to a reduced graphene oxide. The novel 2D reductant has large potential in various in situ nanofabrication applications and this study extends the application of 2D materials to new areas.

Black phosphorus is a biodegradable 2D material that has attracted growing interest in biomedicine. Here, the authors carry out in vitro and in vivoexperiments to demonstrate that nanospheres loaded with black-phosphorus quantum dots perform as promising phothermal cancer therapy agents.

As a layered nano-sheet material, layered graphitic carbon nitride (g-C3N4) has attracted attention in multifunctional photocatalytic applications. However, g-C3N4 is electrochemically inert consequently hampering electrochemical applications. In this work, low-temperature nitrogen plasma processing was conducted to modify g-C3N4 to enhance the electrocatalytic performance in the hydrogen evolution reaction (HER). The plasma produced significant morphological and chemical changes on the surface of g-C3N4 via active species, and nitrogen atoms were incorporated into the surface while the bulk properties did not change. The modification improved the surface hydrophilicity and electrocatalytic HER activity, as well as excellent stability in HER after 2000 cycles. Our results revealed that plasma treatment was a promising technique to improve the HER of carbon-based layered nano-sheet materials.