Covalent Bond Torsion-Enabled Unique Crystal-Phase Transformation of an Organic Semiconductor for Multicolor Light-Emitting Transistors.

High-mobility and color-tunable highly emissive organic semiconductors (OSCs) are highly promising for various optoelectronic device applications and novel structure-property relationship investigations. However, such OSCs have never been reported because of the great trade-off between mobility, emission color, and emission efficiency. Here, we report a novel strategy of molecular conformation-induced unique crystalline polymorphism to realize the high mobility and color-tunable high emission in a novel OSC, 2,7-di(anthracen-2-yl) naphthalene (2,7-DAN). Interestingly, 2,7-DAN has unique crystalline polymorphism, which has an almost identical packing motif but slightly different molecular conformation enabled by the small bond rotation angle variation between anthracene and naphthalene units. More remarkably, the subtle covalent bond rotation angle change leads to a big change in color emission (from blue to green) but does not significantly modify the mobility and emission efficiency. The carrier mobility of 2,7-DAN crystals can reach up to a reliable 17 cm2 V-1 s-1, which is rare for the reported high-mobility OSCs. Based on the unique phenomenon, high-performance light-emitting transistors with blue to green emission are simultaneously demonstrated in an OSC crystal. These results open a new way for designing emerging multifunctional organic semiconductors toward next-generation advanced molecular (atomic)-scale optoelectronics devices.

Pharmacokinetics of Fipaxalparant, a Small-Molecule Selective Negative Allosteric Modulator of Lysophosphatidic Acid Receptor 1, and the Effect of Food in Healthy Volunteers.

Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN-825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open-label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450-mg single dose under fasted conditions or with a high-fat meal. Multiple-dose PKs for twice-daily dosing of either 300 or 450 mg with low- or high-fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose-proportional manner from 150 to 450 mg. At 450 mg, a high-fat meal increased the maximum observed concentration and area under the curve by approximately 1.9- and 2.1-fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies.

Large-Language-Model-Based AI Agent for Organic Semiconductor Device Research.

Large language models (LLMs) have attracted widespread attention recently, however, their application in specialized scientific fields still requires deep adaptation. Here, an artificial intelligence (AI) agent for organic field-effect transistors (OFETs) is designed by integrating the generative pre-trained transformer 4 (GPT-4) model with well-trained machine learning (ML) algorithms. It can efficiently extract the experimental parameters of OFETs from scientific literature and reshape them into a structured database, achieving precision and recall rates both exceeding 92%. Combined with well-trained ML models, this AI agent can further provide targeted guidance and suggestions for device design. With prompt engineering and human-in-loop strategies, the agent extracts sufficient information of 709 OFETs from 277 research articles across different publishers and gathers them into a standardized database containing more than 10 000 device parameters. Using this database, a ML model based on Extreme Gradient Boosting is trained for device performance judgment. Combined with the interpretation of the high-precision model, the agent has provided a feasible optimization scheme that has tripled the charge transport properties of 2,6-diphenyldithieno[3,2-b:2',3'-d]thiophene OFETs. This work is an effective practice of LLMs in the field of organic optoelectronic devices and expands the research paradigm of organic optoelectronic materials and devices.

Effective glioblastoma immune sonodynamic treatment mediated by macrophage cell membrane cloaked biomimetic nanomedicines.

Glioblastoma (GBM) as one of the most lethal brain tumours, remains poor therapeutic index due to its typical characters including heterogeneous, severe immune suppression as well as the existence of blood brain barrier (BBB). Immune sonodynamic (ISD) therapy combines noninvasive sonodynamic therapy with immunotherapy, which has great prospects for the combinational treatment of GBM. Herein, we develop macrophage cell membrane cloaked reactive oxygen species (ROS) responsive biomimetic nanoparticles, co-delivering of sonosensitizer Ce6 and JQ1 (a bromo-domain protein 4 (BRD4) inhibitor which can down-regulate PD-L1) and realizing potent GBM ISD therapy. The ApoE peptide decorated macrophage membrane coating endows these biomimetic nanoparticles with low immunogenicity, efficient BBB permeability, prolonged blood circulation half-live and good biocompatibility. The ROS responsive polymeric inner core could be readily degraded as triggered by excessive ROS under the ultrasound once they accumulated in tumour cells, fast release encapsulated drugs. The generation of ROS not only killed tumour cells via sonodynamic therapy, but also induced immunogenic cell death (ICD) and further activated the anti-tumour immune response. The released JQ1 inhibited tumour cell proliferation and augmented the immune activities by inhibiting the PD-L1 expression on the surface of tumour cells. The cascade sonodynamic and immune therapy resulted in significantly improved median survival time in both orthotopic GL261 and PTEN deficient immunosuppressive CT2A GBM mice models. Therefore, our developed biomimetic nanoparticle platform provides a promising combinational therapy strategy to treat immune suppressive GBM.

Use of statins and risks of ovarian, uterine, and cervical diseases: a cohort study in the UK Biobank.

PURPOSE: To examine the associations between use of statins and risks of various ovarian, uterine, and cervical diseases, including ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome, endometriosis, endometrial hyperplasia, endometrial polyp, and cervical polyp. METHODS: We conducted a cohort study among female participants in the UK Biobank. Information on the use of statins was collected through verbal interview. Outcome information was obtained by linking to national cancer registry data and hospital inpatient data. We used Cox proportional hazards regression to examine the associations. RESULTS: A total of 180,855 female participants (18,403 statin users and 162,452 non-users) were included. Use of statins was significantly associated with increased risks of cervical cancer (adjusted hazard ratio (HR), 1.55; 95% confidence interval (95% CI), 1.05-2.30) and polycystic ovarian syndrome (adjusted HR, 4.39; 95% CI, 1.68-11.49). However, we observed no significant association between use of statins and risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial hyperplasia, endometrial polyp, or cervical polyp. CONCLUSION: Our findings suggest that use of statins is associated with increased risks of cervical cancer and polycystic ovarian syndrome, but is not associated with increased or decreased risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial polyp, or cervical polyp.

Unraveling the crucial role of trace oxygen in organic semiconductors.

Optoelectronic properties of semiconductors are significantly modified by impurities at trace level. Oxygen, a prevalent impurity in organic semiconductors (OSCs), has long been considered charge-carrier traps, leading to mobility degradation and stability problems. However, this understanding relies on the conventional deoxygenation methods, by which oxygen residues in OSCs are inevitable. It implies that the current understanding is questionable. Here, we develop a non-destructive deoxygenation method (i.e., de-doping) for OSCs by a soft plasma treatment, and thus reveal that trace oxygen significantly pre-empties the donor-like traps in OSCs, which is the origin of p-type characteristics exhibited by the majority of these materials. This insight is completely opposite to the previously reported carrier trapping and can clarify some previously unexplained organic electronics phenomena. Furthermore, the de-doping results in the disappearance of p-type behaviors and significant increase of n-type properties, while re-doping (under light irradiation in O2) can controllably reverse the process. Benefiting from this, the key electronic characteristics (e.g., polarity, conductivity, threshold voltage, and mobility) can be precisely modulated in a nondestructive way, expanding the explorable property space for all known OSC materials.

Superhydrophilic Triazine-Based Covalent Organic Frameworks via Post-Modification of FeOOH Clusters for Boosted Photocatalytic Performance.

The triazine-based covalent organic frameworks (tCOF), an intriguing subtype of COFs, are expected as highly promising photocatalysts for various photocatalytic applications owing to their fully conjugated structures and nitrogen-rich skeletons. However, the inherent hydrophobicity and fast recombination of photoexcited electron-hole pairs are two main factors hindering the application of tCOF in practical photocatalytic reactions. Here, a post-synthetic modification strategy to fabricate superhydrophilic tCOF-based photocatalysts is demonstrated by in situ growing FeOOH clusters on TaTz COF (TaTz-FeOOH) for efficient photocatalytic oxidation of various organic pollutants. The strong polar FeOOH endows TaTz-FeOOH with good hydrophilic properties. The well-defined heterogeneous interface between FeOOH and TaTz allows the photoelectrons generated by TaTz to be consumed by Fe (III) to transform into Fe (II), synergistically promoting the separation of holes and the generation of free radicals. Compared with the unmodified TaTz, the optimized TaTz-FeOOH (1%) shows excellent photocatalytic performance, where the photocatalytic degrade rate (k) of rhodamine B is increased by about 12 times, and the degradation rate is maintained at 99% after 5 cycles, thus achieving efficient removal of quinolone antibiotics from water. This study provides a new avenue for the development of COF-based hydrophilic functional materials for a wide range of practical applications.

Quantitative image analysis of intracellular protein translocation in 3-dimensional tissues for pharmacodynamic studies of immunogenic cell death.

A recent development in cancer chemotherapy is to use cytotoxics to induce tumor-specific immune response through immunogenic cell death (ICD). In ICD, calreticulin is translocated from endoplasmic reticulum to cell membrane (ecto-CRT) which serves as the 'eat-me-signal' to antigen-presenting cells. Ecto-CRT measurements, e.g., by ecto-CRT immunostaining plus flow cytometry, can be used to study the pharmacodynamics of ICD in single cells, whereas ICD studies in intact 3-dimensional tissues such as human tumors require different approaches. The present study described a method that used (a) immunostaining with fluorescent antibodies followed by confocal microscopy to obtain the spatial locations of two molecules-of-interest (CRT and a marker protein WGA), and (b) machine-learning (trainable WEKA segmentation) and additional image processing tools to locate the target molecules, remove the interfering signals in the nucleus, cytosol and extracellular space, enable the distinction of the inner and outer edges of the cell membrane and thereby identify the cells with ecto-CRT. This method, when applied to 3-dimensional human bladder cancer cell spheroids, yielded drug-induced ecto-CRT measurements that were qualitatively comparable to the flow cytometry results obtained with single cells disaggregated from spheroids. This new method was applied to study drug-induced ICD in short-term cultures of surgical specimens of human patient bladder tumors.

Ultrahigh-gain organic transistors based on van der Waals metal-barrier interlayer-semiconductor junction.

Intrinsic gain is a vital figure of merit in transistors, closely related to signal amplification, operation voltage, power consumption, and circuit simplification. However, organic thin-film transistors (OTFTs) targeted at high gain have suffered from challenges such as narrow subthreshold operating voltage, low-quality interface, and uncontrollable barrier. Here, we report a van der Waals metal-barrier interlayer-semiconductor junction-based OTFT, which shows ultrahigh performance including ultrahigh gain of ~104, low saturation voltage, negligible hysteresis, and good stability. The high-quality van der Waals-contacted junctions are mainly attributed to patterning EGaIn liquid metal electrodes by low-energy microfluidic processes. The wide-bandgap semiconductor Ga2O3 as barrier interlayer is achieved by in situ surface oxidation of EGaIn electrodes, allowing for an adjustable barrier height and expected thermionic emission properties. The organic inverters with a high gain of 5130 and a simplified current stabilizer are further demonstrated, paving a way for high-gain and low-power organic electronics.

Functional Covalent Organic Framework (COF) Nanoparticles for Biomimic Mineralization and Bacteria Inhabitation.

Biomimic mineralization of hard tissues with hierarchical structures is a challenging task, while designing multifunctional materials possessing both the ability of biomimic mineralization and drug delivery is even more difficult. Herein, inspired by the multilevel structure and mineralization ability of amelogenin, a novel carboxyl-functionalized covalent organic framework (COF) nanosphere material was designed and synthesized, which exhibited a significant biomimetic remineralization ability as demonstrated on SiO2 glass, Ti6Al4V, and an acid-etched enamel surface. Furthermore, the nanoporous structure also enables the COF nanospheres to serve as a drug delivery system for the controlled release of antibacterial drugs. This work provides a promising strategy for the design of multifunctional biomimic materials.

Oxygen-Induced Lattice Strain for High-Performance Organic Transistors with Enhanced Stability.

Integrating the merits of low cost, flexibility, and large-area processing, organic semiconductors (OSCs) are promising candidates for the next-generation electronic materials. The mobility and stability are the key figures of merit for its practical application. However, it is greatly challenging to improve the mobility and stability simultaneously owing to the weak interactions and poor electronic coupling between OSCs molecules. Here, an oxygen-induced lattice strain (OILS) strategy is developed to achieve OSCs with both high mobility and high stability. Utilizing the strategy, the maximum mobility of dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) organic field-effect transistor (OFET) rises to 15.3 cm2  V-1  s-1 and the contact resistance lowers to 25.5 Ω cm. Remarkably, the thermal stability of DNTT is much improved, and a record saturated power density of ≈3.4 × 104  W cm-2 is obtained. Both the experiments and theoretical calculations demonstrate that the lattice compressive strain induced by oxygen is responsible for their high performance and stability. Furthermore, the universality of the strategy is manifested in both n-type and p-type small OSCs. This work provides a novel strategy to improve both the mobility and the stability of OSCs, paving the way for the practical applications of organic devices.

Oxygen-Induced Barrier Lowering for High-Performance Organic Field-Effect Transistors.

Organic field-effect transistors (OFETs) have the advantages of low-cost, large-area processing and could be utilized in a variety of emerging applications. However, the generally large contact resistance (Rc) limits the integration and miniaturization of OFETs. The Rc is difficult to reduce due to an incompatibility between obtaining strong orbit coupling and the barrier height reduction. In this study, we developed an oxygen-induced barrier lowering strategy by introducing oxygen (O2) into the nanointerface between the electrodes and organic semiconductors layer and achieved an ultralow channel width-normalized Rc (Rc·W) of 89.8 Ω·cm and a high mobility of 11.32 cm2 V-1 s-1. This work demonstrates that O2 adsorbed at the nanointerface of metal-semiconductor contact can significantly reduce the Rc from both experiments and theoretical simulations and provides guidance for the construction of high-performance OFETs, which is conducive to the integration and miniaturization of OFETs.

Cancer cell-mitochondria hybrid membrane coated Gboxin loaded nanomedicines for glioblastoma treatment.

Glioblastoma (GBM) remains the most lethal malignant tumours. Gboxin, an oxidative phosphorylation inhibitor, specifically restrains GBM growth by inhibiting the activity of F0F1 ATPase complex V. However, its anti-GBM effect is seriously limited by poor blood circulation, the blood brain barrier (BBB) and non-specific GBM tissue/cell uptake, leading to insufficient Gboxin accumulation at GBM sites, which limits its further clinical application. Here we present a biomimetic nanomedicine (HM-NPs@G) by coating cancer cell-mitochondria hybrid membrane (HM) on the surface of Gboxin-loaded nanoparticles. An additional design element uses a reactive oxygen species responsive polymer to facilitate at-site Gboxin release. The HM camouflaging endows HM-NPs@G with unique features including good biocompatibility, improved pharmacokinetic profile, efficient BBB permeability and homotypic dual tumour cell and mitochondria targeting. The results suggest that HM-NPs@G achieve improved blood circulation (4.90 h versus 0.47 h of free Gboxin) and tumour accumulation (7.73% ID/g versus 1.06% ID/g shown by free Gboxin). Effective tumour inhibition in orthotopic U87MG GBM and patient derived X01 GBM stem cell xenografts in female mice with extended survival time and negligible side effects are also noted. We believe that the biomimetic Gboxin nanomedicine represents a promising treatment for brain tumours with clinical potential.

Clinical comparative analysis of monophasic and multiphasic acute disseminated encephalomyelitis in adults.

Introduction: This study aims to explore the clinical features and prognostic factors for relapse of acute disseminated encephalomyelitis (ADEM) in adults. Material and methods: 56 patients with ADEM were retrospectively analyzed. The epidemiological characteristics, clinical manifestations, laboratory features, magnetic resonance imaging (MRI), treatment and prognosis data of these patients were analyzed using the χ2 test for categorical variables and Mann-Whitney U-test for continuous variables. Then, the clinical characteristics and recurrence factors were summarized. Results: 56 patients with ADEM, based on the criteria of the International Pediatric Multiple Sclerosis Study Group, were recruited to the study. Among these patients, 31 were male and 25 were female. Furthermore, 13 patients had multiphasic ADEM, and 29 patients (52%) had definite incentive factors before onset. The commonest presenting symptoms and signs were fever (36%), disturbance of consciousness (52%), mental disorder (38%), seizure (14%), headache and dizziness (43%), optic neuritis (34%), autonomic nervous system symptoms (43%), limb paralysis or abnormal sensation (73%), and unilateral or bilateral pyramidal tract signs (48%). Inflammatory changes in the cerebrospinal fluid were prominent. MRI T2-weighted and fluid-attenuated inversion recovery images displayed multiple or large flaky high signals, and the lesions were usually different in the number and distribution of these lesions. Intravenous corticosteroids and/or immunoglobulin were still important treatments in the acute phase. After treatment, 38 patients completely recovered, 9 patients had neurologic deficits, and 9 patients died. Conclusions: ADEM in adults is not uncommon, its clinical features are complex and varied, and some of these are multiphasic. There may be some potential clinical predictors at first onset.

Prediction of university fund revenue and expenditure based on fuzzy time series with a periodic factor.

Financial management and decision-making of universities play an essential role in their development. Predicting fund revenue and expenditure of universities can provide a necessary basis for funds risk prevention. For the lack of solid data reference for financial management and funds risk prevention in colleges and universities, this paper presents a prediction model of University fund revenue and expenditure based on fuzzy time series with a periodic factor. Combined with the fuzzy time series, this prediction method introduces the periodic factor of university funds. The periodic factor is used to adjust the proportion of the predicted value of the fuzzy time series and the periodic observation value. A fund revenue prediction model and a fund expenditure prediction model are constructed, and an experiment is carried out with the actual financial data of a university in China. The experimental result shows the effectiveness of the proposed model, which can provide solid references for financial management and funds risk prevention in universities.

Adverse health consequences of undiagnosed hearing loss at middle age: A prospective cohort study with the UK Biobank.

OBJECTIVES: Hearing impairment is common in the middle-aged population but remains largely undiagnosed and untreated. The knowledge about to what extent and how hearing impairment matters for health is currently lacking. Thus, we aimed to comprehensively examine the adverse health consequences as well as the comorbidity patterns of undiagnosed hearing loss. STUDY DESIGN: Based on the prospective cohort of the UK Biobank, we included 14,620 individuals (median age 61 years) with audiometry-determined (i.e., speech-in-noise test) objective hearing loss and 38,479 individuals with subjective hearing loss (i.e., tested negative but with self-reported hearing problems; median age 58 years) at recruitment (2006-2010), together with 29,240 and 38,479 matched unexposed individuals respectively. MAIN OUTCOME MEASURES: Cox regression was used to determine the associations of both hearing-loss exposures with the risk of 499 medical conditions and 14 cause-specific deaths, adjusting for ethnicity, annual household income, smoking and alcohol intake, exposure to working noise, and BMI. Comorbidity patterns following both exposures were visualized by comorbidity modules (i.e., sets of connected diseases) identified in the comorbidity network analyses. RESULTS: During a median follow-up of 9 years, 28 medical conditions and mortality related to nervous system disease showed significant associations with prior objective hearing loss. Subsequently, the comorbidity network identified four comorbidity modules (i.e., neurodegenerative, respiratory, psychiatric, and cardiometabolic diseases), with the most pronounced association noted for the module related to neurodegenerative diseases (meta-hazard ratio [HR] = 2.00, 95%confidence interval [CI] 1.67-2.39). For subjective hearing loss, we found 57 associated medical conditions, which were partitioned into four modules (i.e., diseases related to the digestive, psychiatric, inflammatory, and cardiometabolic systems), with meta-HRs varying from 1.17 to 1.25. CONCLUSIONS: Undiagnosed hearing loss captured by screening could identify individuals with at greater risk of multiple adverse health consequences, highlighting the importance of screening for speech-in-noise hearing impairment in the middle-aged population, for potential early diagnosis and intervention.

A new dithieno[3,2-b:2',3'-d]thiophene derivative for high performance single crystal organic field-effect transistors and UV-sensitive phototransistors.

Organic phototransistors (OPTs), as the basic unit for organic image sensors, are emerging as one of the most promising light signal detectors. High performance UV-sensitive phototransistors are highly desired for the detection of UV light. Herein, by introducing the anthracene group to the 2,6-positions of dithieno[3,2-b:2',3'-d]thiophene, we designed and synthesized a new dithieno[3,2-b:2',3'-d]thiophene derivative, 2,6-di(anthracen-2-yl)dithieno[3,2-b:2',3'-d]thiophene (2,6-DADTT). The single crystal structure of 2,6-DADTT presents classical herringbone packing with multiple intermolecular interactions, including S⋯S (3.470 Å), S⋯C (3.304 Å, 3.391 Å, 3.394 Å) and C-H⋯π (2.763 Å, 2.822 Å, 2.846 Å, 2.865 Å, 2.885 Å, 2.890 Å) contacts. Single crystal organic field-effect transistors (SC-OFETs) based on 2,6-DADTT reach a highest mobility of 1.26 cm2 V-1 s-1 and an average mobility of 0.706 cm2 V-1 s-1. 2,6-DADTT-based single crystal organic phototransistors (OPTs) demonstrate photosensitivity (P) of 2.49 × 106, photoresponsivity (R) of 6.84 × 103 A W-1 and ultrahigh detectivity (D*) of 4.70 × 1016 Jones to UV light, which are among the best figures of merit for UV-sensitive OPTs. These excellent comprehensive performances indicate its good application prospects in integrated optoelectronics.