A programmable hybrid digital chemical information processor based on the Belousov-Zhabotinsky reaction.

The exponential growth of the power of modern digital computers is based upon the miniaturization of vast nanoscale arrays of electronic switches, but this will be eventually constrained by fabrication limits and power dissipation. Chemical processes have the potential to scale beyond these limits by performing computations through chemical reactions, yet the lack of well-defined programmability limits their scalability and performance. Here, we present a hybrid digitally programmable chemical array as a probabilistic computational machine that uses chemical oscillators using Belousov-Zhabotinsky reaction partitioned in interconnected cells as a computational substrate. This hybrid architecture performs efficient computation by distributing information between chemical and digital domains together with inbuilt error correction logic. The efficiency is gained by combining digital logic with probabilistic chemical logic based on nearest neighbour interactions and hysteresis effects. We demonstrated the computational capabilities of our hybrid processor by implementing one- and two-dimensional Chemical Cellular Automata demonstrating emergent dynamics of life-like entities called Chemits. Additionally, we demonstrate hybrid probabilistic logic as a viable logic for solving combinatorial optimization problems.

Orexin recruits non-selective cationic conductance and endocannabinoid to dynamically modulate firing of caudal pontine reticular nuclear neurones.

The neuropeptide orexin is involved in motor circuit function. However, its modulation on neuronal activities of motor structures, integrating orexin's diverse downstream molecular cascades, remains elusive. By combining whole-cell patch-clamp recordings and neuropharmacological methods, we revealed that both non-selective cationic conductance (NSCC) and endocannabinoids (eCBs) are recruited by orexin signalling on reticulospinal neurones in the caudal pontine reticular nucleus (PnC). The orexin-NSCC cascade provides a depolarizing force that proportionally enhances the firing-responsive gain of these neurones. Meanwhile, the orexin-eCB cascade selectively attenuates excitatory synaptic strength in these neurones by activating presynaptic cannabinoid receptor type 1. This cascade restrains the firing response of the PnC reticulospinal neurones to excitatory inputs. Intriguingly, non-linear or linear interactions between orexin postsynaptic excitation and presynaptic inhibition can influence the firing responses of PnC reticulospinal neurones in different directions. When presynaptic inhibition is in the lead, non-linear interactions can prominently downregulate or even gate the firing response. Conversely, linear interactions occur to promote the firing response, and these linear interactions can be considered a proportional reduction in the contribution of depolarization to firing by presynaptic inhibition. Through the dynamic employment of these interactions, adaptive modulation may be achieved by orexin to restrain or even gate the firing output of the PnC to weak/irrelevant input signals and facilitate those to salient signals. KEY POINTS: This study investigated the effects of orexin on the firing activity of PnC reticulospinal neurones, a key element of central motor control. We found that orexin recruited both the non-selective cationic conductances (NSCCs) and endocannabinoid (eCB)-cannabinoid receptor type 1 (CB1R) system to pontine reticular nucleus (PnC) reticulospinal neurones. The orexin-NSCC cascade exerts a postsynaptic excitation that enhances the firing response, whereas the orexin-eCB-CB1R cascade selectively attenuates excitatory synaptic strength that restrains the firing response. The postsynaptic and presynaptic actions of orexins occur in an overlapping time window and interact to dynamically modulate firings in PnC reticulospinal neurones. Non-linear interactions occur when presynaptic inhibition of orexin is in the lead, and these interactions can prominently downregulate or even gate firing responses in PnC reticulospinal neurones. Linear interactions occur when postsynaptic excitation of orexin is in the lead, and these interactions can promote the firing response. These linear interactions can be considered a proportional reduction of the contribution of depolarization to firing by presynaptic inhibition.

An Accelerated Method for Investigating Spectral Properties of Dynamically Evolving Nanostructures.

The discrete-dipole approximation (DDA) is widely applied to study the spectral properties of plasmonic nanostructures. However, the high computational cost limits the application of DDA in static geometries, making it impractical for investigating spectral properties during structural transformations. Here we developed an efficient method to simulate spectra of dynamically evolving structures by formulating an iterative calculation process based on the rank-one decomposition of matrices and DDA. By representing structural transformation as the change of dipoles and their properties, the updated polarizations can be computed efficiently. The improvement in computational efficiency was benchmarked, demonstrating up to several hundred times acceleration for a system comprising ca. 4000 dipoles. The rank-one decomposition accelerated DDA method (RD-DDA) can be used directly to investigate the optical properties of nanostructural transformations defined by atomic- or continuum-scale processes, which is essential for understanding the growth mechanisms of nanoparticles and algorithm-driven structural optimization toward enhanced optical properties.

LINC00665:A Promising Biomarker in Gastrointestinal Tumors.

An increasing volume of studies has reported that long non-codingRNAs (lncRNAs) are involved in the carcinogenesis of many different cancers. Especially in gastrointestinal tumors, lncRNAs are found to participate in various physiological and pathological processes. LncRNAs can regulate gene expression at multiple levels, including transcriptional, post-transcription, translational, and post-translational levels. Long intergenic non-protein coding RNA 665(LINC00665), a novel cancer-related lncRNA, is frequently dysregulated in multiple gastrointestinal tumors, including gastric and colorectal cancers, hepatocellular carcinoma, and so on. In this review, we analyzed the expression and prognostic value of LINC00665 in human gastrointestinal tumors, systematically summarized the current literature about the clinical significance of this lncRNA, and explored the regulatory mechanisms of LINC00665 as a competing endogenous RNA (ceRNA) in tumor progression. Consequently, we concluded that LINC00665 might act as a prognostic biomarker and a potential target for gastrointestinal tumor diagnosis and treatment.

An artificial intelligence enabled chemical synthesis robot for exploration and optimization of nanomaterials.

We present an autonomous chemical synthesis robot for the exploration, discovery, and optimization of nanostructures driven by real-time spectroscopic feedback, theory, and machine learning algorithms that control the reaction conditions and allow the selective templating of reactions. This approach allows the transfer of materials as seeds between cycles of exploration, opening the search space like gene transfer in biology. The open-ended exploration of the seed-mediated multistep synthesis of gold nanoparticles (AuNPs) via in-line ultraviolet-visible characterization led to the discovery of five categories of nanoparticles by only performing ca. 1000 experiments in three hierarchically linked chemical spaces. The platform optimized nanostructures with desired optical properties by combining experiments and extinction spectrum simulations to achieve a yield of up to 95%. The synthetic procedure is outputted in a universal format using the chemical description language (χDL) with analytical data to produce a unique digital signature to enable the reproducibility of the synthesis.

Lactate receptor HCAR1 regulates cell growth, metastasis and maintenance of cancer­specific energy metabolism in breast cancer cells.

Under aerobic conditions, the preferential use of anaerobic glycolysis by tumour cells leads to a high level of lactate accumulation in tumour microenvironment. Lactate acts not only as a cellular energy source but also as a signalling molecule that regulates cancer cell growth, metastasis and metabolism. It has been reported that a G­protein­coupled receptor for lactate named hydroxycarboxylic acid receptor 1 (HCAR1) is highly expressed in numerous types of cancer, but the detailed mechanism remains unclear. In the present study, it was reported that HCAR1 is highly expressed in breast cancer cells. Genetic deletion of HCAR1 in MCF7 cells leads to reduced cell proliferation and migration. Moreover, it was observed that knockout (KO) of HCAR1 attenuated the expression and activity of phosphofructokinase and hexokinase, key rate­limiting enzymes in glycolysis. Using an extracellular flux analyzer, it was showed that KO of HCAR1 promoted a metabolic shift towards a decreased glycolysis state, as evidenced by a decreased extracellular acidification rate and increased oxygen consumption rate in MCF7 cells. Taken together, our results suggested that lactate acts through HCAR1 as a metabolic regulator in breast cancer cells that may be therapeutically exploited.

A three-dimensional matrix system containing melatonin and neural stem cells repairs damage from traumatic brain injury in rats.

Brain lesions can cause neural stem cells to activate, proliferate, differentiate, and migrate to the injured area. However, after traumatic brain injury, brain tissue defects and microenvironment changes greatly affect the survival and growth of neural stem cells; the resulting reduction in the number of neural stem cells impedes effective repair of the injured area. Melatonin can promote the survival, proliferation, and differentiation of neural stem cells under adverse conditions such as oxidative stress or hypoxia that can occur after traumatic brain injury. Therefore, we investigated the therapeutic effects of melatonin combined with neural stem cells on traumatic brain injury in rats. First, in vitro studies confirmed that melatonin promoted the survival of neural stem cells deprived of oxygen and glucose. Then, we established a three-dimensional Matrigel-based transplantation system containing melatonin and neural stem cells and then used it to treat traumatic brain injury in rats. We found that treatment with the Matrigel system containing melatonin and neural stem cells decreased brain lesion volume, increased the number of surviving neurons, and improved recovery of neurological function compared with treatment with Matrigel alone, neural stem cells alone, Matrigel and neural stem cells combined, and Matrigel and melatonin combined. Our findings suggest that the three-dimensional Matrigel-based transplantation system containing melatonin and neural stem cells is a potential treatment for traumatic brain injury.

Efficacy and toxicity of SEAM (semustine, etoposide, cytarabine, and melphalan) conditioning regimen followed by autologous stem cell transplantation in lymphoma.

OBJECTIVES: The aim of this retrospective study was to evaluate the safety and efficacy of SEAM regimen followed by auto-SCT in lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with lymphoma who underwent auto-SCT with SEAM conditioning regimen from January 2010 to June 2018 at our centre. In total, 97 patients were analysed. RESULTS: The median time to neutrophil engraftment and platelet engraftment was 9.5 days (range, 7-15 days) and 12 days (range, 7-25 days), respectively. Grade 3-4 nausea/vomiting, mucositis and diarrhoea were observed in 21.6%, 36.1%, and 11.3% of patients, respectively. Treatment-related mortality at 100 days occurred in 2 patients (2.1%). After a median follow-up time of 53.9 months, the 3-year incidence of disease relapse or progression was 34%. The estimated progression-free survival and overall survival at 3 years were 62% and 75%, respectively. Compared with previous studies using BEAM as the conditioning regimen, this study shows that the SEAM regimen has a comparable efficacy and safety profile. CONCLUSIONS: The SEAM regimen is feasible and might be an ideal alternative to BEAM regimen for lymphoma auto-SCT.

A general method for searching for homometric structures.

The discovery of the homometry of X-ray diffraction dates back to the 1930s and shows the ambiguity in structure characterization purely from diffraction technologies. Since then, there has only been limited discussion on this topic with reference to several real structures and an efficient method for finding homometric structures for a known three-dimensional structure is still lacking today. In this work, a method was developed to create a set of structures with the same interatomic distances as an original structure, which can then be identified as powder X-ray diffraction or single-crystal X-ray diffraction homometric structures. This method was applied to the Inorganic Crystal Structure Database (ICSD) and homometric structures for 37 reported structures were found. Also it was found that homometric structures are encountered frequently in solving crystal structures when building initial models with only heavy atoms, which indicates that special caution is needed in interpreting XRD data with heavy-atom methods.

Association between postoperative hypoalbuminemia and postoperative pulmonary imaging abnormalities patients undergoing craniotomy for brain tumors: a retrospective cohort study.

Hypoalbuminemia is associated with poor outcome in patients undergoing surgery intervention. The main aim for this study was to investigate the incidence and the risk factors of postoperative hypoalbuminemia and assessed the impact of postoperative hypoalbuminemia on complications in patients undergoing brain tumor surgery. This retrospective study included 372 consecutive patients who underwent brain tumors surgery from January 2017 to December 2019. The patients were divided into hypoalbuminemia (< 35 g/L) and non-hypoalbuminemia group (≥ 35 g/L) based on postoperative albumin levels. Logistic regression analyses were used to determine risk factors. Of the total 372 patients, 333 (89.5%) developed hypoalbuminemia after surgery. Hypoalbuminemia was associated with operation time (OR 1.011, P < 0.001), preoperative albumin (OR 0.864, P = 0.015) and peroperative globulin (OR 1.192, P = 0.004). Postoperative pulmonary imaging abnormalities had a higher incidence in patients with than without hypoalbuminemia (41.1% vs 23.1%, P = 0.029). The independent predictors of postoperative pulmonary imaging abnormalities were age (OR 1.053, P < 0.001), operation time (OR 1.003, P = 0.013) and lower postoperative albumin (OR 0.946, P = 0.018). Pulmonary imaging abnormalities [OR 19.862 (95% CI 2.546-154.936, P = 0.004)] was a novel independent predictors of postoperative pneumonia. Postoperative hypoalbuminemia has a higher incidence with the increase of operation time, and may be associated with postoperative complications in patients undergoing brain tumor surgery.

Clinical features and treatment outcomes of 14 patients with hepatosplenic γ δ T-cell lymphoma.

BACKGROUND: Hepatosplenic γ δ T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma (PTCL) with aggressive clinical behavior. To date, no standard therapy for HSTCL has been established. This study analyzed the clinical features, treatment, and prognosis for patients with HSTCL to determine the best therapeutic approach. METHODS: We reviewed the clinical characteristics, treatments, and responses to treatment of patients in our center between January 2001 and June 2021, and also reviewed related literature. RESULTS: Median patient age was 38 years (range 16-60 years) and the patients included eight males and six females. HSTCL in these patients typically presented with B symptoms (71.4%), splenomegaly (100%), and hepatomegaly (50.0%), but lymphadenopathy was extremely rare. In these patients, routine laboratory testing showed elevated lactate dehydrogenase (71.4%), liver dysfunction (42.9%), and decreased fibrinogen (35.7%). In the induction phase, five of the 14 patients received chemotherapy regimens containing anthracycline (CHOP, or CHOP plus bortezomib or Chidamide), and six were treated with non-CHOP chemotherapy. Seven patients responded to induction treatment, four of whom received allogeneic hematopoietic cell transplantation and then achieved a complete response in the consolidation phase. survival time of patients who received alloHCT range from 10 to 27 months. CONCLUSION: Hepatosplenic γ δ T-cell lacks a standard therapy and is often refractory to conventional chemotherapy regimens. Intensive induction chemotherapy followed by hematopoietic cell transplantation may improve the prognosis of HSTCL.

White matter repair and treatment strategy after intracerebral hemorrhage.

The predilection site of intracerebral hemorrhage (ICH) is in the basal ganglia, which is rich in white matter (WM) fiber bundles, such as cerebrospinal tract in the internal capsule. ICH induced damage to this area can easily lead to severe neurological dysfunction and affects the prognosis and quality of life of patients. At present, the pathophysiological mechanisms of white matter injury (WMI) after ICH have attracted researchers' attention, but studies on the repair and recovery mechanisms and therapy strategies remain rare. In this review, we mainly summarized the WM recovery and treatment strategies after ICH by updating the WMI-related content by reviewing the latest researches and proposing the bottleneck of the current research.

All-Inorganic Quantum-Dot Light-Emitting Diodes with Reduced Exciton Quenching by a MgO Decorated Inorganic Hole Transport Layer.

Here, wide-bandgap magnesium oxide (MgO) is employed as a decorator for the nickel oxide (NiO x) hole transport layer (HTL), by means of a bulk dopant as well as a surface modifier. QLEDs with Ni0.88Mg0.12O x serving as the HTL achieve an ∼19.5% efficiency improvement compared to devices using pristine NiO x. Further inserting an ultrathin MgO layer between the Ni0.88Mg0.12O x and QDs to separate the accumulated charges from excitons goes on boosting the peak efficiency by another ∼35%. Finally, a maximum brightness over 40 000 cd/m2 at 10 V is obtained, which is the highest among the reported values.

Modified BuCy is an alternative conditioning regimen for lymphoma patients undergoing autologous stem cell transplantation.

The aim of this study is to determine whether the modified BuCy (semustine, cytarabine, busulfan, and cyclophosphamide, mBuCy) conditioning regimen can be safely used as an alternative to the SEAM (semustine, etoposide, cytarabine, and melphalan) regimen by comparing the efficacy and toxicity of the mBuCy and SEAM regimens. We matched 34 pairs of patients with regard to disease status at the time of autologous stem cell transplantation (auto-SCT). We found no significant difference in the time of platelet engraftment between the two groups. Furthermore, neutrophil engraftment was somewhat faster in the mBuCy group than in the SEAM group (median: 9 days vs 10 days, p = 0.015). With regard to toxicity, the incidence of nausea/vomiting, hepatic impairment, renal impairment, pulmonary infection, and treatment-related mortality (TRM) was similar between the two groups. In addition, compared to patients conditioned with SEAM, patients conditioned with mBuCy were less likely to develop mucositis and diarrhea (p = 0.027; p = 0.050). The 2-year progression-free survival (PFS) rates in the mBuCy and SEAM groups were 79% and 70% (p = 0.378), respectively, and the 2-year overall survival (OS) rates were 81% and 78.0%, respectively (p = 0.789). These analyses showed that the mBuCy conditioning regimen was well tolerated and can be used as an alternative to the SEAM regimen for lymphoma.

Beyond OLED: Efficient Quantum Dot Light-Emitting Diodes for Display and Lighting Application.

The unique features of solution-processed quantum dots (QDs) including emission tunability in the visible range, high-quality saturated color and outstanding intrinsic stability in environment are highly desired in various application fields. Especially, for the preparation of wide color gamut displays, QDs with high photoluminescence quantum yield are deemed as the optimal fluorescent emitter that has been utilized in the backlight for liquid crystal display. Nevertheless, the commercialization of electrically driven self-emissive quantum dot light-emitting diode (QLED) display is the ultimate target due to its merits of high contrast, slim configuration and compatibility with flexible substrate. Through the great efforts devoted to material engineering and device configuration, astonishing progresses have been made in device performance, giving the QLED technology a great chance to compete with other counterparts for next-generation displays. In this review, we retrospect the development roadmap of QLED technology and introduce the essential principles in the QLED devices. Moreover, we discuss the key factors that affect the QLED efficiency and lifetime. Finally, the advances in device architectures and pixel patterning are also summarized.

Simulating Powder X-ray Diffraction Patterns of Two-Dimensional Materials.

Powder X-ray diffraction (PXRD) is widely used to study atomic arrangements in ordered materials. The Bragg equation, which describes diffraction of a three-dimensional crystal, fails in two-dimensional (2D) cases. Complete integration of diffraction signals from a continuum instead of discrete directions in the Bragg equation is thus required for proper data interpretation of 2D materials. Furthermore, modeling of preferred orientation of the 2D crystals as well as geometric disorders are also of vital importance. Here, we present a complete integration method in real space (CIREALS) for PXRD simulation of monolayer or multilayer 2D crystals, especially 2D metal-organic layers and 2D covalent organic frameworks. By working in real space instead of reciprocal space, we can readily capture the 2D geometry and preferred orientation of these materials. The predicted PXRD patterns by CIREALS facilitates structure analysis of these new types of 2D material.

Qualitative and Quantitative Detection of PrPSc Based on the Controlled Release Property of Magnetic Microspheres Using Surface Plasmon Resonance (SPR).

Prion protein (PrPSc) has drawn widespread attention due to its pathological potential to prion diseases. In this work, we constructed a novel surface plasmon resonance (SPR) detection assay involving magnetic microspheres (MMs) and its controlled release property, for selective capture, embedding, concentration, and SPR detection of PrPSc with high sensitivity and specificity. Aptamer-modified magnetic particles (AMNPs) were used to specifically capture PrPSc. Amphiphilic copolymer was used to embed the labeled PrPSc and form magnetic microspheres to isolate PrPSc from the external environment. Static magnetic and alternating magnetic fields were used to concentrate and control release the embedded PrPSc, respectively. Finally, the released AMNPs-labeled PrPSc was detected by SPR which was equipped with a bare gold sensing film. A good linear relationship was obtained between SPR responses and the logarithm of PrPSc concentrations over a range of 0.01-1000 ng/mL. The detection sensitivity for PrPSc was improved by 10 fold compared with SPR direct detection format. The specificity of the present biosensor was also determined by PrPC and other reagents as controls. This proposed approach could also be used to isolate and detect other highly pathogenic biomolecules with similar structural characteristics by altering the corresponding aptamer in the AMNPs conjugates.

Overcoming the Limitations of Sputtered Nickel Oxide for High-Efficiency and Large-Area Perovskite Solar Cells.

Perovskite solar cells (PSCs) are one of the promising photovoltaic technologies for solar electricity generation. NiO x is an inorganic p-type semiconductor widely used to address the stability issue of PSCs. Although high efficiency is obtained for the devices employing NiO x as the hole transport layer, the fabrication methods have yet to be demonstrated for industrially relevant manufacturing of large-area and high-performance devices. Here, it is shown that these requirements can be satisfied by using the magnetron sputtering, which is well established in the industry. The limitations of low fill factor and short-circuit current commonly observed in sputtered NiO x -derived PSCs can be overcome through magnesium doping and low oxygen partial pressure deposition. The fabricated PSCs show a high power conversion efficiency of up to 18.5%, along with negligible hysteresis, improved ambient stability, and high reproducibility. In addition, good uniformity is also demonstrated over an area of 100 cm2. The simple and well-established approach constitutes a reliable and scale method paving the way for the commercialization of PSCs.

Outcome of Allogeneic and Autologous Hematopoietic Cell Transplantation for High-Risk Peripheral T Cell Lymphomas: A Retrospective Analysis From a Chinese Center.

Peripheral T cell lymphomas (PTCLs) often carry poor outcomes with conventional chemotherapy, and hematopoietic cell transplantation (HCT) can benefit patients with PTCL. We conducted a retrospective review of 67 patients with PTCL who underwent autologous HCT (autoHCT, n = 43; median age, 40 years) or allogeneic HCT (alloHCT, n = 24; median age, 36.5 years) from 2004 to 2016. With a median follow-up of 27 months, 5-year progression-free survival (PFS) and overall survival (OS) of autoHCT patients were 49% and 57%, respectively. Among alloHCT recipients, the 5-year PFS and OS were 54% and 55%, respectively. When considering incidence of disease relapse or progression (CIR) and nonrelapse mortality (NRM), the 5-year CIR and 1-year NRM of alloHCT recipients were 38% and 18%, respectively, and 58% and 7% for autoHCT patients, respectively. There were no differences between autoHCT and alloHCT in 5-year PFS (P = .499), OS (P = .566), CIR (P = .555), and NRM (P = .202). When specifically examining recipients in primary refractory disease, 3-year PFS rates of autoHCT and alloHCT were 20% and 49% (P = .054); 3-year OS rates were 20% and 53% (P = .042), respectively. Based on these results, we favor proceeding to alloHCT in patients with PTCL in primary refractory disease.