All-Inorganic Perovskite NiTiO3 /Cs3 Sb2 I9 Heterostructure for Photocatalytic CO2 Reduction to CH4 with High Selectivity.

Developing efficient and stable halide perovskite-based photocatalysts for highly selectivity reduction CO2 to valuable fuels remains a significant challenge due to their intrinsic instability. Herein, a novel heterostructure featuring 2D Cs3 Sb2 I9 nanosheets on a 3D flower-like mesoporous NiTiO3 framework using a top-down stepwise membrane fabrication technique is constructed. The unique bilayer heterostructure formed on the 3D mesoporous framework endowed NiTiO3 /Cs3 Sb2 I9 with sufficient and close interface contact, minimizing charge transport distance, and effectively promoting the charge transfer at the interface, thus improving the reaction efficiency of the catalyst surface. As revealed by characterization and calculation, the coupling of Cs3 Sb2 I9 with NiTiO3 facilitates the hydrogenation process during catalytic, directing reaction intermediates toward highly selective CH4 production. Furthermore, the van der Waals forces inherent in the 3D/2D heterostructure with face-to-face contact provide superior stability, ensuring the efficient realization of photocatalytic CO2 reduction to CH4 . Consequently, the optimized 3D/2D NiTiO3 /Cs3 Sb2 I9 heterostructure demonstrates an impressive CH4 yield of 43.4 µmol g-1  h-1 with a selectivity of up to 88.6%, surpassing most reported perovskite-based photocatalysts to date. This investigation contributes to overcoming the challenges of commercializing perovskite-based photocatalysts and paves the way for the development of sustainable and efficient CO2 conversion technologies.

The role of vitamin D receptor in predentin mineralization and dental repair after injury.

Dentin is a permeable and complex tubular composite formed by the mineralization of predentin that mineralization and repair are of considerable clinical interest during dentin homeostasis. The role of Vdr, a receptor of vitamin D, in dentin homeostasis remains unexplored. The aim of the present study was to assess the impact of Vdr on predentin mineralization and dental repair. Vdr-knockout (Vdr-/-) mice models were constructed; histology and immunohistochemistry analyses were conducted for both WT and Vdr-/- mice. The finding revealed a thicker predentin in Vdr-/- mice, characterized by higher expression of biglycan and decorin. A dental injury model was employed to observe tertiary dentin formation in Vdr-/- mice with dental injuries. Results showed that tertiary dentin was harder to form in Vdr-/- mice with dental injury. Over time, heightened pulp invasion was observed at the injury site in Vdr-/- mice. Expression of biglycan and decorin was reduced in the predentin at the injury site in the Vdr-/- mice by immunohistochemistry. Taken together, our results imply that Vdr plays a regulatory role in predentin mineralization and tertiary dentin formation during dentin homeostasis.

Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial.

Derivation of CD7-targeted chimeric antigen receptor (7CAR) T cells often requires genetic manipulations to ablate the CD7 gene or block CD7 cell surface expression. Our novel approach deriving naturally selected 7CAR (NS7CAR) T cells from bulk T cells was able to overcome major fratricide by minimizing accessible CD7 epitopes. The CD7 molecules of NS7CAR T cells were masked or sequestered by the CD7-targeting CAR. Compared with sorted CD7-negative 7CAR T cells and CD7 knocked-out 7CAR T cells, NS7CAR exhibited similar or superior therapeutic properties, including a greater percentage of CAR+ cells and a higher proportion of CD8+ central memory T cells. In our first-in-human phase 1 trial (NCT04572308), 20 patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) (n = 14) and T-cell lymphoblastic lymphoma (T-LBL) (n = 6) were treated with NS7CAR. Nineteen patients achieved minimal residual disease negative complete remission (CR) in the bone marrow (BM) by day 28, and 5 of 9 patients achieved extramedullary CR. With a median follow-up of 142.5 (32-311) days after infusion, 14 patients subsequently received allogeneic hematopoietic stem cell transplant (10 consolidative, 4 salvage) following NS7CAR infusion with no relapses to date. Of the 6 patients who did not receive a transplant, 4 remained in CR at a median time of 54 (32-180) days. Eighteen patients experienced mild cytokine release syndrome (CRS) (grade ≤2), 1 developed grade 3 CRS, and 2 had grade 1 neurotoxicity. These results indicate that NS7CAR-T therapy is a safe and highly effective treatment for T-ALL/LBL. More patients and longer follow-up are needed for validation.

The Musa troglodytarum L. genome provides insights into the mechanism of non-climacteric behaviour and enrichment of carotenoids.

BACKGROUND: Karat (Musa troglodytarum L.) is an autotriploid Fe'i banana of the Australimusa section. Karat was domesticated independently in the Pacific region, and karat fruit are characterized by a pink sap, a deep yellow-orange flesh colour, and an abundance of ß-carotene. Karat fruit showed non-climacteric behaviour, with an approximately 215-day bunch filling time. These features make karat a valuable genetic resource for studying the mechanisms underlying fruit development and ripening and carotenoid biosynthesis. RESULTS: Here, we report the genome of M. troglodytarum, which has a total length of 603 Mb and contains 37,577 predicted protein-coding genes. After divergence from the most recent common ancestors, M. troglodytarum (T genome) has experienced fusion of ancestral chromosomes 8 and 9 and multiple translocations and inversions, unlike the high synteny with few rearrangements found among M. schizocarpa (S genome), M. acuminata (A genome) and M. balbisiana (B genome). Genome microsynteny analysis showed that the triplication of MtSSUIIs due to chromosome rearrangement may lead to the accumulation of carotenoids and ABA in the fruit. The expression of duplicated MtCCD4s is repressed during ripening, leading to the accumulation of α-carotene, ß-carotene and phytoene. Due to a long terminal repeat (LTR)-like fragment insertion upstream of MtERF11, karat cannot produce large amounts of ethylene but can produce ABA during ripening. These lead to non-climacteric behaviour and prolonged shelf-life, which contributes to an enrichment of carotenoids and riboflavin. CONCLUSIONS: The high-quality genome of M. troglodytarum revealed the genomic basis of non-climacteric behaviour and enrichment of carotenoids, riboflavin, flavonoids and free galactose and provides valuable resources for further research on banana domestication and breeding and the improvement of nutritional and bioactive qualities.

Dephasing Dynamics in a Non-Equilibrium Fluctuating Environment.

We performed a theoretical study of the dephasing dynamics of a quantum two-state system under the influences of a non-equilibrium fluctuating environment. The effect of the environmental non-equilibrium fluctuations on the quantum system is described by a generalized random telegraph noise (RTN) process, of which the statistical properties are both non-stationary and non-Markovian. Due to the time-homogeneous property in the master equations for the multi-time probability distribution, the decoherence factor induced by the generalized RTN with a modulatable-type memory kernel can be exactly derived by means of a closed fourth-order differential equation with respect to time. In some special limit cases, the decoherence factor recovers to the expression of the previous ones. We analyzed in detail the environmental effect of memory modulation in the dynamical dephasing in four types of dynamics regimes. The results showed that the dynamical dephasing of the quantum system and the conversion between the Markovian and non-Markovian characters in the dephasing dynamics under the influence of the generalized RTN can be effectively modulated via the environmental memory kernel.

Reparative effect of super active platelet combined with allogeneic bone for large bone defects.

In clinical practice, autologous bone transplantation is usually used to treat large-scale bone defects. However, autologous bone can cause complications such as secondary injury to patients, the scarcity of autografts. In this study, the study of using super active platelet lysate (sPL) and allogeneic bone to treat the 15 mm long bone defect in right radius of rabbits, and provide an experimental basis for the next step of clinical bone defect treatment. The critical-size defect of New Zealand white rabbits was made and divided into three groups: autologous bone group, allogeneic bone group, and sPL group. They were euthanized 1, 2, and 3 months after the operation, perform imaging and histological observation on the repair of bone defect area. The results showed that there were varying degrees of new bone in the bone defect. CT data showed that the bone defect repair rate and new bone mass in each group increased month by month (P <.05). Bone tissue (BV) and bone tissue to the total volume (BV/TV, %) in the sPL group > allogeneic bone group, autologous bone group > allogeneic bone group, with statistical significance (P < .05). Compared with the allogeneic bone group, the sPL group can significantly promote the healing of bone defects, enhance the bone density after fracture healing. The repair effect after 3 months was similar to that of the autogenous bone group. The use of allogeneic bone and sPL therapy may become part of a comprehensive strategy for tissue engineering to treat bone defects.

An Entropy Metric for Regular Grammar Classification and Learning with Recurrent Neural Networks.

Recently, there has been a resurgence of formal language theory in deep learning research. However, most research focused on the more practical problems of attempting to represent symbolic knowledge by machine learning. In contrast, there has been limited research on exploring the fundamental connection between them. To obtain a better understanding of the internal structures of regular grammars and their corresponding complexity, we focus on categorizing regular grammars by using both theoretical analysis and empirical evidence. Specifically, motivated by the concentric ring representation, we relaxed the original order information and introduced an entropy metric for describing the complexity of different regular grammars. Based on the entropy metric, we categorized regular grammars into three disjoint subclasses: the polynomial, exponential and proportional classes. In addition, several classification theorems are provided for different representations of regular grammars. Our analysis was validated by examining the process of learning grammars with multiple recurrent neural networks. Our results show that as expected more complex grammars are generally more difficult to learn.

Shapley Homology: Topological Analysis of Sample Influence for Neural Networks.

Data samples collected for training machine learning models are typically assumed to be independent and identically distributed (i.i.d.). Recent research has demonstrated that this assumption can be problematic as it simplifies the manifold of structured data. This has motivated different research areas such as data poisoning, model improvement, and explanation of machine learning models. In this work, we study the influence of a sample on determining the intrinsic topological features of its underlying manifold. We propose the Shapley homology framework, which provides a quantitative metric for the influence of a sample of the homology of a simplicial complex. Our proposed framework consists of two main parts: homology analysis, where we compute the Betti number of the target topological space, and Shapley value calculation, where we decompose the topological features of a complex built from data points to individual points. By interpreting the influence as a probability measure, we further define an entropy that reflects the complexity of the data manifold. Furthermore, we provide a preliminary discussion of the connection of the Shapley homology to the Vapnik-Chervonenkis dimension. Empirical studies show that when the zero-dimensional Shapley homology is used on neighboring graphs, samples with higher influence scores have a greater impact on the accuracy of neural networks that determine graph connectivity and on several regular grammars whose higher entropy values imply greater difficulty in being learned.

Impaired D2 receptor-dependent dopaminergic transmission in prefrontal cortex of awake mouse model of Parkinson's disease.

The loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson's disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Parkinson's disease remain largely unexplored. Using two-photon microscopic Ca2+ imaging in awake PARK7-/- and PARK7+/+ mice, we found that (i) PARK7-/- neurons in the frontal association cortex showed substantially higher circuit activity recorded as spontaneous somatic Ca2+ signals; (ii) both basal and evoked dopamine release remained intact, as determined by both electrochemical dopamine recordings and high performance liquid chromatography in vivo; (iii) D2 receptor expression was significantly decreased in postsynaptic frontal association cortical neurons, and the hyper-neuronal activity were rescued by D2 receptor intervention using either local pharmacology or viral D2 receptor over-expression; and (iv) PARK7-/- mice showed anxiety-like behaviours that were rescued by either local D2 receptor pharmacology or overexpression. Thus, for first time, we demonstrated a robust D2 receptor-dependent phenotype of individual neurons within the prefrontal cortex circuit in awake parkinsonian mice that linked with anxiety. Our work sheds light on early-onset phenotypes and the mechanisms underlying Parkinson's disease by imaging brain circuits in an awake mouse model.

Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor-modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia.

Ninety percent of relapse/refractory B-cell acute lymphatic leukemia (R/R B-ALL) patients can achieve complete remission (CR) after CD19-targeting chimeric antigen receptor T (CAR-T) cell therapy. However, around 50% of them relapse in 1 year. Persistent CAR-T cell engraftment is considered as the key to remain durable remission. Here, we initiated a phase I study to treat 10 pediatric B-ALL patients using a CD19-targeted second generation CAR with a 4-1BB intracellular costimulatory domain. All patients received a standard fludarabine and cyclophosphamide (FC) preconditioning regiment, followed by a CAR-T infusion with a median number of 0.5 (0.3-1.58) × 106 CAR+ T cells/kg. The pretreatment tumor burdens were high with a median bone marrow (BM) blasts percentage of 59.2% (7.31%-86.2%), excluding one patient only with brain infiltration of leukemia cells (0% BM blasts). The initial CR rate was 80% (n = 8/10). Four patients (40%) experienced serious (grade > 2) cytokine release syndrome (CRS) and three patients (30%) with obvious neurotoxicity. Monthly assessments of CD19+ minimal residual disease (MRD) and CAR-T engraftment demonstrated the anti-CD19 activity of long-term engrafted CAR-T cell clones in one patient for more than 2 years.

Comparison of Anthraquinones, Iridoid Glycosides and Triterpenoids in Morinda officinalis and Morinda citrifolia Using UPLC/Q-TOF-MS and Multivariate Statistical Analysis.

Roots of Morinda officinalis and Morinda citrifolia have been interchangeably used in traditional Chinese medicine. However, there is no experimental evidence to support this. In this study, a ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS)-based approach and a multivariate statistical analysis (MSA) were adopted to compare the difference in the chemical compounds present in the root extract of M. officinalis and M. citrifolia. There were 26 anthraquinones, 15 triterpenes, and 8 iridoid glycosides identified in the root extracts of M. officinalis, 30 anthraquinones, 1 triterpene, and 8 iridoid glycosides in the root extracts of M. citrifolia. Among these, 25 compounds presented in both plants. In addition, a principal component analysis (PCA) showed that these two herbs could be separated clearly. Furthermore, an orthogonal partial least squares-discriminant analysis (OPLS-DA) found 9 components that could be used as chemical markers to discrimination the root extracts of M. officinalis and M. citrifolia. In addition, the results of a Cell Counting Kit 8 (CCK-8) assay and cell colony formation assay indicated that methanol root extracts of M. officinalis and M. citrifolia showed no cell cytotoxicity to normal cells, even promoted the proliferation of normal liver cells. To our knowledge, this is the first time that the differences between the root extracts of M. officinalis and M. citrifolia (Hainan province) have been observed systematically at the chemistry level.

[Present situation and development strategy of Alpinia oxyphylla].

Alpinia oxyphylla is mainly produced in Hainan,and also one of the four famous traditional Chinese medicines in South China with increasing importance in traditional Chinese medicine industry. Field surveys and literatures show that A. oxyphylla has widely used as a medicinal and edible plant,it is an important raw material for many Chinese patent medicines,health products and food,with a long history of artificial cultivation and application. The future development is prospected on health market. But A. oxyphylla industry has faced a lot of problems,including unreasonable planting layout,lack of good varieties,imperfect seed breeding system,low level of standardization,inconsistent quality of medicinal materials,low level of industry,and so on. The suggestions for sustainable development are listed below.First,it is essential to strengthen the research on the basis and application technology of A. oxyphylla,speed up the selection and breeding of improved varieties,and popularize standardized cultivation techniques. Secondly,it is important to strengthen the research on quality standards,improve the quality evaluation system of medicinal materials. Thirdly,it is necessary to take full advantage of the functional components to develop functional products with Hainan characteristics,find out the unique product characteristics of A. oxyphylla,build a famous brand and improve the product competitiveness in the market. It is also important to strengthen policy support and industrial supervision,promote the healthy and rapid development of A. oxyphylla industry.

An Empirical Evaluation of Rule Extraction from Recurrent Neural Networks.

Rule extraction from black box models is critical in domains that require model validation before implementation, as can be the case in credit scoring and medical diagnosis. Though already a challenging problem in statistical learning in general, the difficulty is even greater when highly nonlinear, recursive models, such as recurrent neural networks (RNNs), are fit to data. Here, we study the extraction of rules from second-order RNNs trained to recognize the Tomita grammars. We show that production rules can be stably extracted from trained RNNs and that in certain cases, the rules outperform the trained RNNs.

Metabolic Reprogramming in Chloroplasts under Heat Stress in Plants.

Increases in ambient temperatures have been a severe threat to crop production in many countries around the world under climate change. Chloroplasts serve as metabolic centers and play a key role in physiological adaptive processes to heat stress. In addition to expressing heat shock proteins that protect proteins from heat-induced damage, metabolic reprogramming occurs during adaptive physiological processes in chloroplasts. Heat stress leads to inhibition of plant photosynthetic activity by damaging key components functioning in a variety of metabolic processes, with concomitant reductions in biomass production and crop yield. In this review article, we will focus on events through extensive and transient metabolic reprogramming in response to heat stress, which included chlorophyll breakdown, generation of reactive oxygen species (ROS), antioxidant defense, protein turnover, and metabolic alterations with carbon assimilation. Such diverse metabolic reprogramming in chloroplasts is required for systemic acquired acclimation to heat stress in plants.

Visible-Light-Driven BiOI-Based Janus Micromotor in Pure Water.

Light-driven synthetic micro-/nanomotors have attracted considerable attention due to their potential applications and unique performances such as remote motion control and adjustable velocity. Utilizing harmless and renewable visible light to supply energy for micro-/nanomotors in water represents a great challenge. In view of the outstanding photocatalytic performance of bismuth oxyiodide (BiOI), visible-light-driven BiOI-based Janus micromotors have been developed, which can be activated by a broad spectrum of light, including blue and green light. Such BiOI-based Janus micromotors can be propelled by photocatalytic reactions in pure water under environmentally friendly visible light without the addition of any other chemical fuels. The remote control of photocatalytic propulsion by modulating the power of visible light is characterized by velocity and mean-square displacement analysis of optical video recordings. In addition, the self-electrophoresis mechanism has been confirmed for such visible-light-driven BiOI-based Janus micromotors by demonstrating the effects of various coated layers (e.g., Al2O3, Pt, and Au) on the velocity of motors. The successful demonstration of visible-light-driven Janus micromotors holds a great promise for future biomedical and environmental applications.

Putative zeatin O-glucosyltransferase OscZOG1 regulates root and shoot development and formation of agronomic traits in rice.

As a ubiquitous reaction, glucosylation controls the bioactivity of cytokinins in plant growth and development. Here we show that genetic manipulation of zeatin-O-glucosylation regulates the formation of important agronomic traits in rice by manipulating the expression of OscZOG1 gene, encoding a putative zeatin O-glucosyltransferase. We found that OscZOG1 was preferentially expressed in shoot and root meristematic tissues and nascent organs. The growth of lateral roots was stimulated in the overexpression lines, but inhibited in RNA interference lines. In shoots, knockdown of OscZOG1 expression by RNA interference significantly improved tillering, panicle branching, grain number per panicle and seed size, which are important agronomic traits for grain yield. In contrast, constitutive expression of OscZOG1 leads to negative effects on the formation of the grain-yielding traits with a marked increase in the accumulation levels of cis-zeatin O-glucoside (cZOG) in the transgenic rice plants. In this study, our findings demonstrate the feasibility of improving the critical yield-determinant agronomic traits, including tiller number, panicle branches, total grain number per panicle and grain weight by downregulating the expression level of OscZOG1. Our results suggest that modulating the levels of cytokinin glucosylation can function as a fine-tuning switch in regulating the formation of agronomic traits in rice.

Nanomaterials-based optical techniques for the detection of acetylcholinesterase and pesticides.

The large amount of pesticide residues in the environment is a threat to global health by inhibition of acetylcholinesterase (AChE). Biosensors for inhibition of AChE have been thus developed for the detection of pesticides. In line with the rapid development of nanotechnology, nanomaterials have attracted great attention and have been intensively studied in biological analysis due to their unique chemical, physical and size properties. The aim of this review is to provide insight into nanomaterial-based optical techniques for the determination of AChE and pesticides, including colorimetric and fluorescent assays and surface plasmon resonance.

Golm1 facilitates the CaO2-DOPC-DSPE200-PEI -CsPbBr3 QDs -induced apoptotic death of hepatocytes through the stimulation of mitochondrial autophagy and mitochondrial reactive oxygen species production through interactions with P53/Beclin-1/Bcl-2.

Mitophagy is a distinct physiological process that can have beneficial or deleterious effects in particular tissues. Prior research suggests that mitophagic activity can be triggered by CaO2-PM-CsPbBr3 QDs, yet the specific role that mitophagy plays in hepatic injury induced by CaO2-PM-CsPbBr3 QDs has yet to be established. Accordingly, in this study a series of mouse model- and cell-based experiments were performed that revealed the ability of CaO2-PM-CsPbBr3 QDs to activate mitophagic activity. Golm1 was upregulated in response to CaO2-PM-CsPbBr3 QDs treatment, and overexpressing Golm1 induced autophagic flux in the murine liver and hepatocytes, whereas knocking down Golm1 had the opposite effect. CaO2-PM-CsPbBr3 QDs were also able to Golm1 expression, in turn promoting the degradation of P53 and decreasing the half-life of this protein. Overexpressing Golm1 was sufficient to suppress the apoptotic death of hepatocytes in vitro and in vivo, whereas the knockdown of Golm1 had the opposite effect. The ability of Golm1 to promote p53-mediated autophagy was found to be associated with the disruption of Beclin-1 binding to Bcl-2, and the Golm1 N-terminal domain was determined to be required for p53 interactions, inducing autophagic activity in a manner independent of helicase activity or RNA binding. Together, these results indicate that inhibiting Golm1 can promote p53-dependent autophagy via disrupting Beclin-1 binding to Bcl-2, highlighting a novel approach to mitigating liver injury induced by CaO2-PM-CsPbBr3 QDs.

Boosting Interfacial Electron Transfer and CO2 Enrichment on ZIF-8/ZnTe for Selective Photoelectrochemical Reduction of CO2 to CO.

Artificial photosynthesis is an effective way of converting CO2 into fuel and high value-added chemicals. However, the sluggish interfacial electron transfer and adsorption of CO2 at the catalyst surface strongly hamper the activity and selectivity of CO2 reduction. Here, we report a photocathode attaching zeolitic imidazolate framework-8 (ZIF-8) onto a ZnTe surface to mimic an aquatic leaf featuring stoma and chlorophyll for efficient photoelectrochemical conversion of CO2 into CO. ZIF-8 possessing high CO2 adsorption capacity and diffusivity has been selected to enrich CO2 into nanocages and provide a large number of catalytic active sites. ZnTe with high light-absorption capacity serves as a light-absorbing layer. CO2 molecules are collected in large nanocages of ZIF-8 and delivered to the ZnTe surface. As evidenced by scanning electrochemical microscopy, the interface can effectively boost interfacial electron transfer kinetics. The ZIF-8/ZnTe photocathode with unsaturated Zn-Nx sites exhibits a high Faradaic efficiency for CO production of 92.9% and a large photocurrent of 6.67 mA·cm-2 at -2.48 V (vs Fc/Fc+) in a nonaqueous electrolyte at AM 1.5G solar irradiation (100 mW·cm-2).

Insect-Scale Biped Robots Based on Asymmetrical Friction Effect Induced by Magnetic Torque.

Multimodal and controllable locomotion in complex terrain is of great importance for practical applications of insect-scale robots. Robust locomotion plays a particularly critical role. In this study, a locomotion mechanism for magnetic robots based on asymmetrical friction effect induced by magnetic torque is revealed and defined. The defined mechanism overcomes the design constraints imposed by both robot and substrate structures, enabling the realization of multimodal locomotion on complex terrains. Drawing inspiration from human walking and running locomotion, a biped robot based on the mechanism is proposed, which not only exhibits rapid locomotion across substrates with varying friction coefficients but also achieves precise locomotion along patterned trajectories through programmed controlling. Furthermore, apart from its exceptional locomotive capabilities, the biped robot demonstrates remarkable robustness in terms of load-carrying and weight-bearing performance. The presented locomotion and mechanism herein introduce a novel concept for designing magnetic robots while offering extensive possibilities for practical applications in insect-scale robotics.