Creating Organic Functional Materials beyond Chemical Bond Synthesis by Organic Cocrystal Engineering.

Organic cocrystal engineering refers to two or more organic molecules stoichiometrically combined and held together by noncovalent intermolecular interactions, which differs from standard chemical synthesis involving covalent bond breakage and formation. Organic cocrystals have unique properties and offer a new strategy for creating enhanced organics. First, however, some key questions need to be addressed: How do diverse monomers affect the intermolecular interaction kinetics during cocrystallization? How do the intermolecular forces in cocrystals affect cocrystal functions? In this Perspective, the definition and advantages of organic cocrystal engineering, specifically in the construction of a reliable intermolecular interaction-stacking structure-performance relationship, are outlined. Additionally, recent developments in the field and the questions above are discussed. Finally, a brief conclusion and some hints on likely future developments are provided.

Organic crystalline materials in flexible electronics.

Flexible electronics have attracted considerable attention recently given their potential to revolutionize human lives. High-performance organic crystalline materials (OCMs) are considered strong candidates for next-generation flexible electronics such as displays, image sensors, and artificial skin. They not only have great advantages in terms of flexibility, molecular diversity, low-cost, solution processability, and inherent compatibility with flexible substrates, but also show less grain boundaries with minimal defects, ensuring excellent and uniform electronic characteristics. Meanwhile, OCMs also serve as a powerful tool to probe the intrinsic electronic and mechanical properties of organics and reveal the flexible device physics for further guidance for flexible materials and device design. While the past decades have witnessed huge advances in OCM-based flexible electronics, this review is intended to provide a timely overview of this fascinating field. First, the crystal packing, charge transport, and assembly protocols of OCMs are introduced. State-of-the-art construction strategies for aligned/patterned OCM on/into flexible substrates are then discussed in detail. Following this, advanced OCM-based flexible devices and their potential applications are highlighted. Finally, future directions and opportunities for this field are proposed, in the hope of providing guidance for future research.

Thermally Activated Delayed Fluorescence in an Organic Cocrystal: Narrowing the Singlet-Triplet Energy Gap via Charge Transfer.

Harvesting non-emissive spin-triplet charge-transfer (CT) excitons of organic semiconductors is fundamentally important for increasing the operation efficiency of future devices. Here we observe thermally activated delayed fluorescence (TADF) in a 1:2 CT cocrystal of trans-1,2-diphenylethylene (TSB) and 1,2,4,5-tetracyanobenzene (TCNB). This cocrystal system is characterized by absorption spectroscopy, variable-temperature steady-state and time-resolved photoluminescence spectroscopy, single-crystal X-ray diffraction, and first-principles calculations. These data reveal that intermolecular CT in cocrystal narrows the singlet-triplet energy gap and therefore facilitates reverse intersystem crossing (RISC) for TADF. These findings open up a new way for the future design and development of novel TADF materials.

Molecular cocrystals: design, charge-transfer and optoelectronic functionality.

Organic cocrystals, formed by a combination of electron-rich donors and electron-poor acceptors, play an important role in tailoring the optoelectronic properties of molecular materials. Charge transfer interactions in cocrystals not only endow them with an ordered three-dimensional (3D) supramolecular network in different constituent units, but also render them ideal scaffolds to control the intermolecular interactions in multicomponent solids. In this perspective, we firstly introduce preparation methods, molecular packing modes and charge transfer in organic cocrystals. Then, we focus on the novel and promising optoelectronic properties of organic cocrystals based on charge transfer interactions. Finally, we briefly discuss the outlook for the future development of these multicomponent crystalline materials.

Intermolecular Charge-Transfer Interactions Facilitate Two-Photon Absorption in Styrylpyridine-Tetracyanobenzene Cocrystals.

Cocrystals of 4-styrylpyridine and 1,2,4,5-tetracyanobenzene were successfully prepared by supramolecular self-assembly. Donor-acceptor interactions between the molecular components are the main driving force for self-assembly and contribute to intermolecular charge transfer. The cocrystals possess two-photon absorption properties that are not observed in the individual components; suggesting that two-photon absorption originates from intermolecular charge-transfer interactions in the donor-acceptor system. The origin of two-photon absorption in multichromophore systems remains under-researched; thus, the system offers a rare demonstration of two-photon absorption by cocrystallization. Cocrystal engineering may facilitate further design and development of novel materials for nonlinear optical and optoelectronic applications.

Uncovering the Intramolecular Emission and Tuning the Nonlinear Optical Properties of Organic Materials by Cocrystallization.

The spectroscopic and photophysical properties of organic materials in the solid-state are widely accepted as a result of their molecular packing structure and intermolecular interactions, such as J- and H-aggregation, charge-transfer (CT), excimer and exciplex. However, in this work, we show that Spe-F4 DIB cocrystals (SFCs) surprisingly retain the energy levels of photoluminescence (PL) states of Spe crystals, despite a significantly altered molecular packing structure after cocrystallization. In comparison, Npe-F4 DIB cocrystals (NFCs) with new spectroscopic states display different spectra and photophysical behaviors as compared with those of individual component crystals. These may be related to the molecular configuration in crystals, and we propose Spe as an "intramolecular emissive" material, thus providing a new viewpoint on light-emitting species of organic chromophores. Moreover, the nonlinear optical (NLO) properties of Npe and Spe are firstly demonstrated and modulated by cocrystallization. The established "molecule-packing-property" relationship helps to rationally control the optical properties of organic materials through cocrystallization.

Analysis of possible factors relating to prognosis in autologous peripheral blood mononuclear cell transplantation for critical limb ischemia.

BACKGROUND AIMS: Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells (M-PBMNCs) has been shown to be effective in treating critical limb ischemia (CLI); however, the studies of the possible prognosis predictors after autologous M-PBMNC transplantation are inadequate. The objective of the study was to assess the possible factors affecting the results of M-PBMNC transplantation for CLI. METHODS: We reviewed the clinical profiles of 87 patients with CLI who were treated with M-PBMNC implantation in the Blood Diseases Hospital, Chinese Academy of Medical Sciences, between December 2002 and December 2011, and we followed these patients. The patients were divided into a good prognosis group and a poor prognosis group on the basis of whether amputation was performed. The significant differences of clinical variables between two groups were analyzed by means of the Mann-Whitney test and χ2 test, and logistic regression analysis was used to study the variables representing the possible prognostic factors for amputation. RESULTS: Of the 87 patients, three patients died and one patient was lost during the follow-up period. We analyzed 83 patients. The diseases included CLI complicated by diabetes mellitus gangrene (35 cases, 42.2%), arteriosclerosis obliterans (31 cases, 37.3%) and thromboangiitis (17 cases, 20.5%). The mean age was 62 years (range, 30-87). The median follow-up time for the surviving patients was 5 years. The 5-year amputation-free rate was 72.2%, and no adverse effects related to M-PBMNC transplantation were observed. CONCLUSIONS: The significant prognostic factors associated with poor angiogenesis were fibrinogen > 4 g/L and fasting blood glucose > 6 mmol/L.

Transformation of Severe Aplastic Anemia into Donor Cell Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Rare Case Report.

BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for severe aplastic anemia (SAA). It is known that SAA can evolve into malignant clonal diseases, such as acute myeloblastic leukemia (AML) or myelodysplastic syndrome. However, the transformation of SAA into AML after allo-HSCT is a rare phenomenon. Here, we report a case of SAA transformed into AML after patient received human leucocyte antigen (HLA)-matched sibling peripheral blood stem cell transplantation. CASE REPORT A 51-year-old female patient presented with petechiae and fatigue and received a diagnosis of idiopathic SAA. The immunosuppressive therapy combined with umbilical cord blood transplantation failed for this patient. Then, she received HLA-matched sibling allogeneic peripheral blood stem cell transplantation (allo-PBSCT). However, 445 days after allo-PBSCT, the patient had a diagnosis of AML by bone marrow puncture. Donor-recipient chimerism monitoring and cytogenetic analysis confirmed that the leukemia was donor cell origin. Notably, a new HOXA11 mutation was detected in the peripheral blood of the patient after transplantation by whole-exome sequencing, which was the same gene mutation detected in the donor. The patient received 1 cycle of induction chemotherapy with azacytidine and achieved complete remission. However, the leukemia relapsed after 2 cycles of consolidation chemotherapy. Unfortunately, the patient died of leukemia progression 575 days after allo-HSCT. CONCLUSIONS The mechanism of how normal donor hematopoietic cells transform to leukemia in the host remains unclear. Donor cell leukemia provides a unique opportunity to examine genetic variations in donors and hosts with regards to the progression to malignancy.

A novel low-temperature evaporation wastewater treatment apparatus based on hydrate adsorption.

Heavy metal pollution is an urgent challenge worldwide due to the acceleration of industrialization. While adsorption desalination is regarded as an innovative method for wastewater treatment, the current technologies have been impeded by high costs and intensive energy consumption. In this work, a novel low-temperature evaporation wastewater treatment apparatus based on hydrate adsorption was proposed. The water vapor from wastewater evaporation reacted with CO2 to form hydrate under the pressure of 3.3 MPa, constantly promoting wastewater evaporation due to the consumption of water vapor. The effect of feeding concentration on treatment effect was analyzed in terms of removal efficiency, water yield, and enrichment factor. Remarkably, a maximum removal efficiency of 97.4% can be achieved by treating an artificial solution with a Cu2+ concentration of 500 mg/L. Furthermore, compared with the control group that only depended on evaporation and condensation without forming hydrate, the maximum water yield of purified water in the experimental group increased to 310%. This innovative design concept for a low-temperature wastewater treatment apparatus based on hydrate adsorption presents a promising solution for the green and energy-efficient treatment of heavy metal wastewater.

Disseminated fusarium infection after allogeneic hematopoietic stem cell transplantation after CART: A case report.

BACKGROUND: Fusarium is a conditional pathogen that can cause invasive infection in patients with hematological diseases under immune function. METHODS: A case of recurrent and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia was treated with allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor-modified T cells treatment. RESULTS: During transplantation, disseminated Fusarium infection occurred, involving the skin, liver, spleen and central nervous system, and the patient eventually died. CONCLUSIONS: Early identification of Fusarium infection based on the characteristic rash and timely antifungal treatment can improve the cure rate.

Challenging Bendable Organic Single Crystal and Transistor Arrays with High Mobility and Durability toward Flexible Electronics.

Bendable organic single crystals are promising candidates for flexible electronics owing to their superior charge-transport properties. However, large-area high-quality organic single crystals are rarely available on the polymer substrates generally used in flexible electronics. Here, a surface-assisted assembly strategy based on a polymer modification, poly(amic acid) (PAA), is developed to grow large-area organic singe crystals on polymer substrates using a simple drop-casting method. The unique surface properties of PAA that enable molecular solution superwetting and promote molecular ordered assembly produce an extraordinary self-driven "meniscus-guided coating" behavior, enabling the fabrication of millimeter-sized, highly aligned organic single crystals for a variety of organic semiconductors. Organic field-effect transistors based on a mode molecule of 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene demonstrate the highest (average) mobility of 18.6 cm2 V-1 s-1 (15.9 cm2 V-1 s-1 ), attractively low operating voltage of -3 V, and high flexible durability. The results shed light on the large-area fabrication of organic single crystals on polymer dielectrics toward high-performance and integrated plastic electronics.

Anthracene Single-Crystal Scintillators for Computer Tomography Scanning.

X-ray imaging and computed tomography (CT) technology, as the important non-destructive measurements, can observe internal structures without destroying the detected sample, which are always used in biological diagnosis to detect tumors, pathologies, and bone damages. It is always a challenge to find materials with a low detection limit, a short exposure time, and high resolution to reduce X-ray damage and acquire high-contrast images. Here, we described a low-cost and high-efficient method to prepare centimeter-sized anthracene crystals, which exhibited intense X-ray radioluminescence with a detection limit of ∼0.108 µGy s-1, which is only one-fifth of the dose typically used for X-ray diagnostics. Additionally, the low absorption reduced the damage in radiation and ensured superior cycle performance. X-ray detectors based on anthracene crystals also exhibited an extremely high resolution of 40 lp mm-1. The CT scanning and reconstruction of a foam sample were then achieved, and the detailed internal structure could be clearly observed. These indicated that organic crystals are expecting to be leading candidate low-cost materials for low-dose and highly sensitive X-ray detection and CT scanning.

Negative Phototransistors with Ultrahigh Sensitivity and Weak-Light Detection Based on 1D/2D Molecular Crystal p-n Heterojunctions and their Application in Light Encoders.

Anomalous negative phototransistors in which the channel current decreases under light illumination hold potential to generate novel and multifunctional optoelectronic applications. Although a variety of design strategies have been developed to construct such devices, NPTs still suffer from far lower device performance compared to well-developed positive phototransistors (PPTs). In this work, a novel 1D/2D molecular crystal p-n heterojunction, in which p-type 1D molecular crystal (1DMC) arrays are embedded into n-type 2D molecular crystals (2DMCs), is developed to produce ultrasensitive NPTs. The p-type 1DMC arrays act as light-absorbing layers to induce p-doping of n-type 2DMCs through charge transfer under illumination, resulting in ineffective gate control and significant negative photoresponses. As a result, the NPTs show remarkable performances in photoresponsivity (P) (1.9 × 108 ) and detectivity (D*) (1.7 × 1017 Jones), greatly outperforming previously reported NPTs, which are one of the highest values among all organic phototransistors. Moreover, the device exhibits intriguing characteristics undiscovered in PPTs, including precise control of the threshold voltage by controlling light signals and ultrasensitive detection of weak light. As a proof-of-concept, the NTPs are demonstrated as light encoders that can encrypt electrical signals by light. These findings represent a milestone for negative phototransistors, and pave the way for the development of future novel optoelectronic applications.

A novel apparatus for measuring gas solubility in aqueous solution under multiphase conditions by isobaric method.

With the increasing energy shortage and global warming, the oil/gas development and CO2 sequestration are moving toward the deep sea, and such a geological environment is conducive to gas hydrate formation. At present, for the gas solubility of a hydrate solution system, only Duan's simulation data are widely accepted, and a systematic experimental study is absent. The conventional measurement instruments for solubility of dissolved gas lack control of hydrate phase change, detailed regulation of temperature and pressure, and liquid-solid separation of sampling analysis. This paper describes the working principle, design, and use of a novel apparatus that can measure gas solubility in the solution system in the presence of hydrate. The application of constant pressure equipment avoids disturbing the phase equilibrium and dissolution equilibrium of the system in the sampling process. The apparatus is attractive for the continuous measurement of gas solubility and the guarantee of high accuracy. In addition, an isobaric method is proposed for gas solubility measurement, which promotes the measurement system to reach the target equilibrium state quickly and obtains highly regular data of gas solubility under environmental conditions. The experimental data obtained by this work are highly consistent with the Duan model, and the relative errors of measurements are within 2%. Gas solubility data from this apparatus will provide theoretical support for estimation of the marine CO2 sequestration capacity and prevention of hydrate blockage in oil/gas transportation.

Organic Semiconductor Single Crystals for X-ray Imaging.

Low-dose, high-resolution X-ray imaging is vital for medical diagnostics and material/device analyses. Current X-ray imagers are dominated by expensive inorganic materials via high-temperature solid processes (up to 1700 °C, e.g., CsI:Tl) with heavy metal elements. It is essential to search for new materials as X-ray imagers with low growth temperature, low cost, high sensitivity, along with high chemical and environmental stability. Here, 9,10-diphenylanthracene (9,10-DPA) single crystals are used as a representative model, which are grown via low-temperature solution processes, exhibiting intense X-ray radioluminescence with ultrahigh photon-conversion efficiency, ultrafast response and high sensitivity. The resolution of devices based on organic crystals exceeds 20.00 lp mm-1 . Meanwhile the crystals exhibit high cycle performance under X-ray irradiation and environmental stability. This study demonstrates that organic semiconductors have potential use in low-cost, high-sensitivity and low-dose X-ray imaging systems.

In-situ observation for natural gas hydrate in porous medium: Water performance and formation characteristic.

Extensive efforts have been made regarding gas hydrate sample reconstruction in the laboratory for a better understanding and development of natural gas resources. Magnetic resonance imaging (MRI) is a useful method for directly observing the reconstruction of methane hydrate, yet relevant studies remain limited. In this study, a 9.4-T 400-MHz MRI instrument was employed to investigate CH4 hydrate formation in porous media involving various initial water saturation levels and sand diameters. Pressure histories and MRI signal variations were monitored to discuss the process of CH4 hydrate growth, and the three main formation stages of induction, rapid growth, and slow formation were determined. Furthermore, the liquid water performance in MRI micro-images was analyzed to predict the characteristics of CH4 hydrate formation. The results indicated that CH4 hydrate formed in a spatially and temporally random manner and that pore plugging occurred owing to the residual water encased in grown hydrate. Additionally, phase saturations, water conversion percentages, and formation rates were defined to evaluate the effect of sand diameter and initial water saturation on CH4 hydrate formation. With the reduction in the diameter of quartz glass beads from 400 µm to 100 µm, the average hydrate formation rate increased from 0.0010 min-1 to 0.0034 min-1, respectively. When the initial water saturation decreased to the optimized value (0.22 in this study), the water conversion percentage and hydrate saturation increased.

Cocrystal Engineering: A Collaborative Strategy toward Functional Materials.

Cocrystal engineering with a noncovalent assembly feature by simple constituent units has inspired great interest and has emerged as an efficient and versatile route to construct functional materials, especially for the fabrication of novel and multifunctional materials, due to the collaborative strategy in the distinct constituent units. Meanwhile, the precise crystal architectures of organic cocrystals, with long-range order as well as free defects, offer the opportunity to unveil the structure-property and charge-transfer-property relationships, which are beneficial to provide some general rules in rational design and choice of functional materials. In this regard, an overview of organic cocrystals in terms of assembly, containing the intermolecular interactions and growth methods, two functionality-related factors including packing structure and charge-transfer nature, and those advanced and novel functionalities, is presented. An outlook of future research directions and challenges for organic cocrystal is also provided.

Analyzing spatially and temporally visualized formation behavior of methane hydrate in unconsolidated porous media.

An understanding of the nucleation and growth mechanism of methane hydrate in porous space is essential for exploitation and application of hydrates, but the mechanism is yet to be clarified. Magnetic resonance imaging (MRI) was employed to visually analyze the spatial and temporal formation behavior of methane hydrate in a porous media. Detailed information about the water distribution, initial nucleation sites, and hydrate growth was obtained, in addition to MRI images. The results demonstrated that the water molecules distributed in the vertical direction preferred the middle slice of a porous medium sample, and the decrease in the number of molecules in the middle slice and on both sides of the slice was similar during hydrate formation. The formation process are quite different in selected horizontal slices, which were contributed to the various distribution of water and gas in pore spaces and the randomness of methane hydrate formation. The extension of these predicted results could have important implications for optimizing the formation processes of gas hydrate in hydrate-based technologies.

3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression.

Three dimensional (3D) culture has gradually become a research hotspot in the field of drug screening, stem cell research, and tissue engineering due to its more physiological-like morphology and function. In this study, we compared the differences of cell proliferation, population, protein expression and chemoresistance profiles between two dimensional (2D) and 3D culture of acute lymphoblastic leukemia (ALL) Jurkat cell line. Polycaprolactone (PCL) is used for 3D culture owing to its biochemical properties and compatibility. Culturing of ALL Jurkat cell line in collagen type I coated polycaprolactone scaffold for 168 h increased cell proliferation, attachment, as well as the drug resistance to cytarabine (Ara-C) and daunorubicin (DNR) without changing the original CD2+CD3+CD4+dimCD8-CD34-CD45+dim phenotype, compared to uncoated PCL scaffold and tissue culture plate systems. Molecularly, increased chemoresistance is associated with the upregulation of discoidin domain receptor 1 (DDR1) and transcription factor STAT3. Inhibition of DDR1 activity by DDR1-specific inhibitor DDR-IN-1 accelerated cell death in the presence of Ara-C, DNR or their combination. These results demonstrated that 3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression. Importantly, the cell adhesion-mediated drug resistance induced by DDR1 in the scaffold was similar to the clinical situation, indicating the 3D culture of cancer cells recapitulate the in vivo tumor environment and this platform can be used as a promising pre-clinic drug-screen system.

Dihydroartemisinin triggers c-Myc proteolysis and inhibits protein kinase B/glycogen synthase kinase 3ß pathway in T-cell lymphoma cells.

Recent studies have revealed a positive therapeutic effect of dihydroartemisinin (DHA) on tumor cells. However, the underlying mechanism of this has not yet been elucidated. The present study examined the potential therapeutic role and mechanism of DHA in T-cell lymphoma cells. It was revealed that DHA inhibited the proliferation of Jurkat and HuT-78 T-cell lymphoma cells in a concentration- and time-dependent manner. Furthermore, DHA reduced c-Myc protein expression at the transcriptional level, and induced the phosphorylation of c-Myc and the degradation of c-Myc oncoprotein levels. DHA treatment resulted in decreased phosphorylation of protein kinase B (Akt) and glycogen synthase 3ß (GSK3ß) in T-cell lymphoma cells. In addition, DHA treatment induced cell apoptosis, which was accompanied by an increased ratio of Bax/Bcl-2. Taken together, the results of the present study suggested that DHA may exert its antitumor role by accelerating c-Myc proteolysis and inhibiting the Akt/GSK3ß pathway in T-cell lymphoma cells.